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Starting new diabetes drugs less likely for racial minorities, Medicare Advantage beneficiaries
, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.
Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.
Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.
“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”
The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.
“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.
Disparities by race in diabetes drug use
The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,
While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.
“This has created some concerns about access in particular for underserved groups,” he said in his presentation.
In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.
They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.
New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.
No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.
“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”
Insurance type and diabetes drugs
Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.
They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.
After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.
Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.
“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.
Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.
SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.
Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.
Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.
“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”
The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.
“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.
Disparities by race in diabetes drug use
The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,
While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.
“This has created some concerns about access in particular for underserved groups,” he said in his presentation.
In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.
They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.
New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.
No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.
“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”
Insurance type and diabetes drugs
Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.
They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.
After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.
Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.
“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.
Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.
SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
, according to researchers at the virtual annual scientific sessions of the American Diabetes Association.
Initiation of DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors was less likely among racial/ethnic minorities and Medicare Advantage beneficiaries in the retrospective analyses, leading the investigators to call for a better understanding of nonclinical factors that may be influencing treatment decisions.
Odds of new diabetes medication use were 55%-69% lower in patients in Medicare Advantage (MA) as compared to patients in commercial health plans, according to results of a separate study presented by Rozalina McCoy, MD, endocrinologist and researcher with Mayo Clinic, Rochester, Minn.
“The rates of use are increasing over time, but not enough in MA beneficiaries,” she said in her virtual presentation. “I think it really calls for more to be done to ensure access to and use of evidence based medications, by all people with type 2 diabetes.”
The likelihood of initiating a new diabetes drug was 29% lower among African Americans and 49% lower among Native Americans in a study of enrollees in the Look AHEAD (Action for Health in Diabetes) randomized trial, according to researcher Ahmed Elhussein, BMBCh, MPH, of the Johns Hopkins Bloomberg School of Public Health.
“This is particularly concerning, because they might have a greater need for these new diabetes medications, but reduced access,” Dr. Elhussein said in his presentation.
Disparities by race in diabetes drug use
The prevalence of type 2 diabetes in the United States is higher among racial and ethnic minorities, at about 12%-15%, versus about 7% in whites, according to Dr. Elhussein,
While the newer classes of diabetes medications have a lower risk of hyperglycemia and have cardiovascular and renal benefits, they also come at a higher cost, he added.
“This has created some concerns about access in particular for underserved groups,” he said in his presentation.
In their retrospective analysis, based on 4,892 patients enrolled in the Look AHEAD (Action for Health in Diabetes) randomized trial, Dr. Elhussein and coinvestigators identified 44% who had initiated a newer diabetes medication over a median follow-up of about 8 years.
They found black race was associated with significantly lower initiation of newer medications compared to whites, with a hazard ratio of 0.81 (95% confidence interval 0.80-0.94; P = 0.019), after adjustment for socioeconomic status.
New diabetes medication use was also significantly lower among American Indian/Alaskan Natives, with an HR of 0.51 and a confidence interval that did not include the null value of 1, according to the investigator.
No significant differences in new diabetes drug use were seen in Hispanics or those classified as other race/ethnicity, he added.
“We’d advocate for more study to try to understand what are the drivers of this disparity,” he said. “This would let us develop interventions that might help to increase access in these patient groups that might need them the most.”
Insurance type and diabetes drugs
Second-line medications, including GLP-1 receptor agonists and SGLT2 inhibitors, have “preferred” efficacy and side effect profiles, but are more costly than older, generic options such as sulfonylureas, which may affect the likelihood of their use, said Dr. McCoy, the Mayo Clinic researcher and lead author of the study on diabetes medication use by insurance type.
They analyzed 1.7 million individuals in a de-identified dataset (OptumLabs Data Warehouse) who were either privately insured or beneficiaries of Medicare Advantage, the private health plan alternative to fee-for-service Medicare.
After adjusting for race/ethnicity, baseline medications, age, gender, and other factors, odds of new medication use were significantly lower in the Medicare Advantage group, according to Dr. McCoy.
Odds ratios ranged from 0.61 (95% CI, 0.60-0.63) for DPP-4 inhibitors, to 0.45 (95% CI, 0.44-0.46) for GLP-1 receptor agonists, and to 0.31 (95% CI, 0.30-0.31) for SGLT2 inhibitors, she reported.
“This may be driven by affordability, because patients with Medicare Advantage plans are not able to access prescription savings cards (as compared to Medicare beneficiaries) and they also are more likely to have fixed incomes and not be able to afford the high costs of these drugs,” she said.
Dr. Elhussein reported no disclosures related to the research, while co-authors provided disclosures related to Abbott, Bigfoot Biomedical, Boehringer Ingelheim, Eli Lilly, MannKind, Medscape, Novo Nordisk, Sanofi US, and others. Dr McCoy likewise had no disclosures, while co-authors indicated disclosures related to Janssen Pharmaceuticals, the Centers for Medicare and Medicaid Services, and the U.S. Food and Drug Administration.
SOURCES: ADA 2020. Authors: McCoy R et al (38-OR), and Elhussein A, et al (37-OR).
FROM ADA 2020
EMPA-REG OUTCOME: Empagliflozin cut insulin need in type 2 diabetes
Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.
“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.
The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.
Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.
For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.
Results add to the ‘risk and benefit conversation’
“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.
Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.
Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
Handelsman: Analysis shows no ‘spectacular effect’
The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.
The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.
The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.
EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.
SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.
Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.
“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.
The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.
Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.
For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.
Results add to the ‘risk and benefit conversation’
“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.
Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.
Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
Handelsman: Analysis shows no ‘spectacular effect’
The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.
The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.
The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.
EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.
SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.
Patients with type 2 diabetes treated with the SGLT2 inhibitor empagliflozin during the landmark EMPA-REG OUTCOME trial had a solidly reduced need to either start insulin treatment or intensify existing insulin treatment, compared with those given placebo, in a post-hoc analysis of the study’s findings.
“Empagliflozin markedly and durably delayed the need for insulin initiation, and reduced the need for large dose increases in patients already using insulin,” Muthiah Vaduganathan, MD, said at the virtual annual scientific sessions of the American Diabetes Association.
The patients in the empagliflozin (Jardiance) arm of EMPA-REG OUTCOME had a 9% rate of initiating insulin treatment after 4 years in the study, compared with a 20% rate among patients who received placebo, a statistically significant 60% relative risk reduction. All patients in the trial continued on their background oral glucose-lowering medications.
Among the 48% of study patients who entered the study already using insulin as part of their usual regimen, 18% of those receiving empagliflozin required a significant increase in their insulin dosage (an increase of at least 20% from baseline) after 4 years. But among the control patients, 35% needed this level of insulin-dosage intensification, again a statistically significant difference that computed to a 58% relative reduction in the need for boosting the insulin dosage.
For both of these endpoints, the divergence between the empagliflozin and control arms became apparent within the first 6 months on treatment, and the between-group differences steadily increased during further follow-up. The analyses pooled the patients who received empagliflozin in the trial, which studied two different dosages of the drug.
Results add to the ‘risk and benefit conversation’
“This is one of the first studies to look at this question in a more granular fashion” in patients with type 2 diabetes receiving a drug from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class, said Dr. Vaduganathan, a cardiologist at Brigham and Women’s Hospital in Boston. It provides “compelling” information to include when discussing oral diabetes-drug options with patients, he said in an interview.
Patients newly diagnosed with type 2 diabetes “often think about insulin” and their potential need to eventually start taking it, with the requirements it brings for training, monitoring, and drug delivery, along with the costs for insulin and glucose monitoring. “Patients are very attuned to potentially needing insulin and often ask about it. A reduced need for insulin will be an important part of the risk and benefit conversation” with patients about potential use of an SGLT2 inhibitor, he said.
Dr. Vaduganathan hypothesized that three factors could contribute to the impact of empagliflozin on insulin initiation and dosage level: a direct glycemic-control effect of the drug, the drug’s positive impact on overall well-being and function that could enhance patient movement, and the documented ability of treatment with empagliflozin and other drugs in its class to cut the rate of heart failure hospitalizations. This last feature is potentially relevant because insulin treatment often starts in patients with type 2 diabetes during a hospitalization, he noted.
Handelsman: Analysis shows no ‘spectacular effect’
The association of empagliflozin treatment with a reduced need for insulin seen in these data is consistent with expectations for patients with type 2 diabetes who receive an additional oral drug, commented Yehuda Handelsman, MD, an endocrinologist and diabetes specialist who is medical director of The Metabolic Institute of American in Tarzana, Calif. “In large part it has to do with patients on placebo having to get more insulin” because their additional oral-drug options were limited. Dr. Handelsman pointed out that during the period when the EMPA-REG OUTCOME trial ran, from 2010-2015, fewer oral drugs were available than today, and clinicians in the study were encouraged to treat patients to their goal glycemia level according to local guidelines. In addition to a modest but useful glycemic control effect from SGLT2 inhibitors that, on average, cut hemoglobin A1c levels by about 0.5%, they may also give a small boost to insulin sensitivity that can also defer the need to add or increase insulin. The level of insulin-treatment deference reported in the new analysis was “not a spectacular effect” he said in an interview.
The EMPA-REG OUTCOME (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) study followed 7,020 patients at 590 sites in 42 countries for a median of 3.1 years. The study’s primary endpoint was a composite of death from cardiovascular causes, nonfatal myocardial infarction (excluding silent MI), or nonfatal stroke, and the results showed a statistically significant 14% relative risk reduction with empagliflozin treatment (N Engl J Med. 2015 Nov 26;373[22]:2117-28 ). The results also showed that 12 weeks into the study, before patients could receive any additional drugs, HbA1c levels averaged 0.54%-0.6% lower among the empagliflozin-treated patients than those in the placebo arm, with smaller between-group differences maintained through the balance of the study. At entry, more than half the enrolled patients were routinely treated with metformin, and close to half were receiving a sulfonyurea agent.
The EMPA-REG OUTCOME results were also notable as showing for the first time that treatment with an SGLT2 inhibitor drug produced a substantial decrease in heart failure hospitalizations, incident heart failure, and progression of renal dysfunction, effects subsequently confirmed and also found for other agents in this drug class.
EMPA-REG OUTCOME was funded in part by Boehringer Ingelheim and Eli Lilly, the companies that market empagliflozin (Jardiance). Dr. Vaduganathan has been an advisor to Boehringer Ingelheim and to Amgen, AstraZeneca, Baxter, Bayer, Cytokinetics, and Relypsa. Dr. Handelsman has been a consultant to several drug companies including Boehringer Ingelheim and Eli Lilly.
SOURCE: Vaduganathan M et al. ADA 2020, Abstract 30-OR.
FROM ADA 2020
Automated insulin delivery system ‘getting better and better’
Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available 670G hybrid closed-loop, particularly in young people with type 1 diabetes, new data suggest.
Automated insulin delivery systems are comprised of an insulin pump, continuous glucose monitor (CGM), and an automated insulin dosing algorithm.
Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented June 12 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions. The AHCL is the algorithm used in Medtronic’s new MiniMed 780G system, which received a CE Mark on June 11 for the treatment of type 1 diabetes in people aged 7 to 80 years.
One trial, presented by Bruce W. Bode, MD, of Atlanta Diabetes Associates, Georgia, was the US pivotal safety study that will be submitted to the US Food and Drug Administration for approval of the Medtronic 780G.
Another trial, presented by Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, was a separate comparison of the AHCL with the 670G. (The AHCL-based system used in the three trials was identical to the 780G except it didn’t include Bluetooth, which will be a feature of the final product.)
A third trial, presented by Martin de Bock, PhD, of the University of Otago, New Zealand, included the CE Mark dataset for the 780G.
In contrast to the 670G, the 780G adds automated correction boluses for high blood glucose levels (rather than simply adjusting the basal infusion) and allows for adjustment of target glucose levels down to 100 mg/dL rather than a minimum of 120 mg/dL.
Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction. And specifically compared to the 670G, the AHCL-based system reverts to open-loop far less often because it only exits closed-loop mode when the sensor stops working or during sensor changes, but not during hyperglycemia even above 300 mg/dL.
Asked to comment, session moderator Timothy S. Bailey, MD, president and CEO of the AMCR Institute, Escondido, California, told Medscape Medical News: “Automated insulin delivery systems are getting better and better.”
“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They all take people from where they are now to better time-in-range, less time with hypoglycemia, and most important, they might make the quality of their lives better. That’s really underappreciated.”
One factor that has allowed for the improvements, Bailey said, is the recognition by regulatory bodies that the hybrid closed-loop devices are generally safer than current open-loop type 1 diabetes management so that fewer “safety” device features that interfere with tight glycemic control are necessary.
With first-generation closed-loop systems, “If a wide variety of conditions occur, users get kicked off [hybrid closed-loop mode]. Originally it was perceived by the regulatory agencies as a safety feature because they perceived the standard of care as safe. The new system was allowed to have fewer rules.”
Pivotal trial: Time-in-range improved, 96% say system easy to use
The goal of the AHCL system is to maximize the time-in-range of blood glucose between 70-180 mg/dL. Automated basal delivery of insulin is programmed to a set-point of 100 or 120 mg/dL, with dosing every 5 minutes.
The US pivotal trial was a single-arm, 16-center, in-home trial of 157 people with type 1 diabetes, including 39 adolescents aged 14-21 years and 118 adults aged 22-75 years. All had type 1 diabetes for at least 2 years, A1c levels below 10%, and had been using insulin pumps for at least 6 months, with or without CGMs.
After a 14-day run-in, they wore the systems with a 100 or 120 mg/dL set-point for 45 days, then switched to the other setpoint for another 45 days. Average A1c dropped from 7.5% to 7.0%, with the proportions having an A1c ≤ 7.0% increasing from 34% to 61%.
Overall time-in-range was 75% compared to 69% at baseline, with time below range (< 70 mg/dL) of 1.8%. Overnight time-in-range was 82%, with 1.5% below range. Time-in-range increased from 62% to 73% in the adolescents and from 71% to 75% in the adults.
There were no incidences of severe hypoglycemia or diabetic ketoacidosis, and no device-related serious adverse events.
Participants reported being in hybrid closed-loop, or auto-mode, 95% of the time, compared with 33% for those who had been previously using the 670G.
The number of AHCL exits was 1.3 per week, significantly less than with the 670G. Of those, 29% were user-initiated while the rest were implemented by the device, most often when the sensor wasn’t working.
In a study questionnaire, 96% reported that the system was easy to use.
AHCL vs 670G: Major improvements seen
Bergenstal presented data from the Fuzzy Logic Automated Insulin Regulation (FLAIR) study, funded by the National Institute of Diabetes and Digestive and Kidney Disease, comparing Medtronic’s AHCL-based system with the currently marketed 670G hybrid closed-loop, in 113 individuals with type 1 diabetes aged 14-29 years.
“This age group has traditionally been the most difficult group in which to optimize glucose management,” Bergenstal said.
FLAIR is believed to be the first-ever study comparing an investigational automated insulin delivery system with a commercially approved system, he noted. All participants used each automated insulin delivery system for 3 months in the randomized crossover trial.
The primary outcome, time spent above 180 mg/dL during the day combined with time below 54 mg/dL over 24 hours at baseline with the 670G and AHCL went from 42% to 37% to 34%, respectively, for the former and from 0.46% to 0.50% to 0.45%, respectively, for the latter.
The percentage time-in-range over 24 hours went from 57% at baseline to 67% with the AHCL versus 63% with the 670G. A1c levels dropped from 7.9% at baseline to 7.6% with the 670G and 7.4% with AHCL.
“Remember, these are the adolescents who are the toughest of the tough, yet there was a 10% increase in time-in-range ... this is very clinically significant,” Bergenstal said.
Even among 14 patients who had been using multiple daily injections without CGM prior to the study, a group often excluded from closed-loop studies, time-in-range improved from 45% at baseline to 63% with the 670G to 65% with AHCL.
“I’m making a plea not to exclude people just because they haven’t previously used technology,” Bergenstal said.
One patient who had dosed with extra insulin manually had a severe hypoglycemia event with AHCL. No patient had diabetic ketoacidosis.
The proportion of insulin given as auto-correction boluses was 36%, which is important as it means that the system was compensating for missed meal doses, a common phenomenon among teenagers, Bergenstal noted.
“There is still room for further improvement in glycemic control in this population of patients with type 1 diabetes, but AHCL represents a significant step forward,” he concluded.
New Zealand study: More data in youth show AHCL benefits
Unlike the US study populations of just teens aged 14 and older, and adults, the study data used for approval in the EU — from New Zealand — included a total of 60 patients with 20 children aged 7-15 years. It, too, was a 10-week randomized crossover clinical trial comparing the AHCL to a sensor-augmented pump system with an algorithm only for predictive low-glucose management (PLGM) and no adjustments for high blood glucose.
Time-in-range was 59% at baseline and 58% with PLGM, compared to 70.4% with AHCL, and most of the time-in-range improvement occurred at night. Time below 70 mg/dL dropped from 3.1% to 2.5% to 2.1%, respectively.
Similar to the US studies, participants spent 96% of the time in closed-loop mode with only 1.2 exits per week. On a questionnaire, 95% of patients agreed that the system was easy to use and 85% that the system improved their quality of life.
De Bock showed a slide with some quotes, including one from a parent saying, “We didn’t have to be fearful at night or have that thought when we opened her bedroom door in the morning that she might not be conscious,” and from a patient, “I forgot I had diabetes today.”
Bailey commented: “Of course these devices are not free. So, the challenge is how do we make them available, less expensive, and easy to use? We have our work cut out for us, but this is heartening data. Everything has gotten better but we’re not out of a job yet.”
Bailey has reported receiving research support from Abbott, Capillary Biomedical, Dexcom, Diasome, Eli Lilly, Kowa, Lexicon, Medtronic, Medtrum, Novo Nordisk, REMD, Sanofi, Senseonics, ViaCyte, vTv Therapeutics, Zealand Pharma, and consulting or speaking honoraria from Abbott, LifeScan, Novo Nordisk, Sanofi, and Medtronic. Bode has reported receiving consulting and speaker fees from Medtronic. Bergenstal has reported participating in clinical research, being an advisory board member, and/or serving as a consultant for Abbott Diabetes Care, Ascensia, CeQure, Dexcom, Eli Lilly, Hygieia, Senseonics, and United Healthcare. De Bock has reported receiving honoraria or expenses from Novo Nordisk, Sanofi, Pfizer, Medtronic, and Lilly, and research funds from Novo Nordisk and Medtronic.
This article first appeared on Medscape.com.
Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available 670G hybrid closed-loop, particularly in young people with type 1 diabetes, new data suggest.
Automated insulin delivery systems are comprised of an insulin pump, continuous glucose monitor (CGM), and an automated insulin dosing algorithm.
Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented June 12 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions. The AHCL is the algorithm used in Medtronic’s new MiniMed 780G system, which received a CE Mark on June 11 for the treatment of type 1 diabetes in people aged 7 to 80 years.
One trial, presented by Bruce W. Bode, MD, of Atlanta Diabetes Associates, Georgia, was the US pivotal safety study that will be submitted to the US Food and Drug Administration for approval of the Medtronic 780G.
Another trial, presented by Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, was a separate comparison of the AHCL with the 670G. (The AHCL-based system used in the three trials was identical to the 780G except it didn’t include Bluetooth, which will be a feature of the final product.)
A third trial, presented by Martin de Bock, PhD, of the University of Otago, New Zealand, included the CE Mark dataset for the 780G.
In contrast to the 670G, the 780G adds automated correction boluses for high blood glucose levels (rather than simply adjusting the basal infusion) and allows for adjustment of target glucose levels down to 100 mg/dL rather than a minimum of 120 mg/dL.
Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction. And specifically compared to the 670G, the AHCL-based system reverts to open-loop far less often because it only exits closed-loop mode when the sensor stops working or during sensor changes, but not during hyperglycemia even above 300 mg/dL.
Asked to comment, session moderator Timothy S. Bailey, MD, president and CEO of the AMCR Institute, Escondido, California, told Medscape Medical News: “Automated insulin delivery systems are getting better and better.”
“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They all take people from where they are now to better time-in-range, less time with hypoglycemia, and most important, they might make the quality of their lives better. That’s really underappreciated.”
One factor that has allowed for the improvements, Bailey said, is the recognition by regulatory bodies that the hybrid closed-loop devices are generally safer than current open-loop type 1 diabetes management so that fewer “safety” device features that interfere with tight glycemic control are necessary.
With first-generation closed-loop systems, “If a wide variety of conditions occur, users get kicked off [hybrid closed-loop mode]. Originally it was perceived by the regulatory agencies as a safety feature because they perceived the standard of care as safe. The new system was allowed to have fewer rules.”
Pivotal trial: Time-in-range improved, 96% say system easy to use
The goal of the AHCL system is to maximize the time-in-range of blood glucose between 70-180 mg/dL. Automated basal delivery of insulin is programmed to a set-point of 100 or 120 mg/dL, with dosing every 5 minutes.
The US pivotal trial was a single-arm, 16-center, in-home trial of 157 people with type 1 diabetes, including 39 adolescents aged 14-21 years and 118 adults aged 22-75 years. All had type 1 diabetes for at least 2 years, A1c levels below 10%, and had been using insulin pumps for at least 6 months, with or without CGMs.
After a 14-day run-in, they wore the systems with a 100 or 120 mg/dL set-point for 45 days, then switched to the other setpoint for another 45 days. Average A1c dropped from 7.5% to 7.0%, with the proportions having an A1c ≤ 7.0% increasing from 34% to 61%.
Overall time-in-range was 75% compared to 69% at baseline, with time below range (< 70 mg/dL) of 1.8%. Overnight time-in-range was 82%, with 1.5% below range. Time-in-range increased from 62% to 73% in the adolescents and from 71% to 75% in the adults.
There were no incidences of severe hypoglycemia or diabetic ketoacidosis, and no device-related serious adverse events.
Participants reported being in hybrid closed-loop, or auto-mode, 95% of the time, compared with 33% for those who had been previously using the 670G.
The number of AHCL exits was 1.3 per week, significantly less than with the 670G. Of those, 29% were user-initiated while the rest were implemented by the device, most often when the sensor wasn’t working.
In a study questionnaire, 96% reported that the system was easy to use.
AHCL vs 670G: Major improvements seen
Bergenstal presented data from the Fuzzy Logic Automated Insulin Regulation (FLAIR) study, funded by the National Institute of Diabetes and Digestive and Kidney Disease, comparing Medtronic’s AHCL-based system with the currently marketed 670G hybrid closed-loop, in 113 individuals with type 1 diabetes aged 14-29 years.
“This age group has traditionally been the most difficult group in which to optimize glucose management,” Bergenstal said.
FLAIR is believed to be the first-ever study comparing an investigational automated insulin delivery system with a commercially approved system, he noted. All participants used each automated insulin delivery system for 3 months in the randomized crossover trial.
The primary outcome, time spent above 180 mg/dL during the day combined with time below 54 mg/dL over 24 hours at baseline with the 670G and AHCL went from 42% to 37% to 34%, respectively, for the former and from 0.46% to 0.50% to 0.45%, respectively, for the latter.
The percentage time-in-range over 24 hours went from 57% at baseline to 67% with the AHCL versus 63% with the 670G. A1c levels dropped from 7.9% at baseline to 7.6% with the 670G and 7.4% with AHCL.
“Remember, these are the adolescents who are the toughest of the tough, yet there was a 10% increase in time-in-range ... this is very clinically significant,” Bergenstal said.
Even among 14 patients who had been using multiple daily injections without CGM prior to the study, a group often excluded from closed-loop studies, time-in-range improved from 45% at baseline to 63% with the 670G to 65% with AHCL.
“I’m making a plea not to exclude people just because they haven’t previously used technology,” Bergenstal said.
One patient who had dosed with extra insulin manually had a severe hypoglycemia event with AHCL. No patient had diabetic ketoacidosis.
The proportion of insulin given as auto-correction boluses was 36%, which is important as it means that the system was compensating for missed meal doses, a common phenomenon among teenagers, Bergenstal noted.
“There is still room for further improvement in glycemic control in this population of patients with type 1 diabetes, but AHCL represents a significant step forward,” he concluded.
New Zealand study: More data in youth show AHCL benefits
Unlike the US study populations of just teens aged 14 and older, and adults, the study data used for approval in the EU — from New Zealand — included a total of 60 patients with 20 children aged 7-15 years. It, too, was a 10-week randomized crossover clinical trial comparing the AHCL to a sensor-augmented pump system with an algorithm only for predictive low-glucose management (PLGM) and no adjustments for high blood glucose.
Time-in-range was 59% at baseline and 58% with PLGM, compared to 70.4% with AHCL, and most of the time-in-range improvement occurred at night. Time below 70 mg/dL dropped from 3.1% to 2.5% to 2.1%, respectively.
Similar to the US studies, participants spent 96% of the time in closed-loop mode with only 1.2 exits per week. On a questionnaire, 95% of patients agreed that the system was easy to use and 85% that the system improved their quality of life.
De Bock showed a slide with some quotes, including one from a parent saying, “We didn’t have to be fearful at night or have that thought when we opened her bedroom door in the morning that she might not be conscious,” and from a patient, “I forgot I had diabetes today.”
Bailey commented: “Of course these devices are not free. So, the challenge is how do we make them available, less expensive, and easy to use? We have our work cut out for us, but this is heartening data. Everything has gotten better but we’re not out of a job yet.”
Bailey has reported receiving research support from Abbott, Capillary Biomedical, Dexcom, Diasome, Eli Lilly, Kowa, Lexicon, Medtronic, Medtrum, Novo Nordisk, REMD, Sanofi, Senseonics, ViaCyte, vTv Therapeutics, Zealand Pharma, and consulting or speaking honoraria from Abbott, LifeScan, Novo Nordisk, Sanofi, and Medtronic. Bode has reported receiving consulting and speaker fees from Medtronic. Bergenstal has reported participating in clinical research, being an advisory board member, and/or serving as a consultant for Abbott Diabetes Care, Ascensia, CeQure, Dexcom, Eli Lilly, Hygieia, Senseonics, and United Healthcare. De Bock has reported receiving honoraria or expenses from Novo Nordisk, Sanofi, Pfizer, Medtronic, and Lilly, and research funds from Novo Nordisk and Medtronic.
This article first appeared on Medscape.com.
Medtronic’s next-generation automated insulin delivery system offers significant improvements over the currently available 670G hybrid closed-loop, particularly in young people with type 1 diabetes, new data suggest.
Automated insulin delivery systems are comprised of an insulin pump, continuous glucose monitor (CGM), and an automated insulin dosing algorithm.
Data from three trials of such systems using Medtronic’s advanced hybrid closed-loop (AHCL) algorithm (trade name SmartGuard) were presented June 12 during the virtual American Diabetes Association (ADA) 80th Scientific Sessions. The AHCL is the algorithm used in Medtronic’s new MiniMed 780G system, which received a CE Mark on June 11 for the treatment of type 1 diabetes in people aged 7 to 80 years.
One trial, presented by Bruce W. Bode, MD, of Atlanta Diabetes Associates, Georgia, was the US pivotal safety study that will be submitted to the US Food and Drug Administration for approval of the Medtronic 780G.
Another trial, presented by Richard M. Bergenstal, MD, executive director of the International Diabetes Center at Park Nicollet, Minneapolis, Minnesota, was a separate comparison of the AHCL with the 670G. (The AHCL-based system used in the three trials was identical to the 780G except it didn’t include Bluetooth, which will be a feature of the final product.)
A third trial, presented by Martin de Bock, PhD, of the University of Otago, New Zealand, included the CE Mark dataset for the 780G.
In contrast to the 670G, the 780G adds automated correction boluses for high blood glucose levels (rather than simply adjusting the basal infusion) and allows for adjustment of target glucose levels down to 100 mg/dL rather than a minimum of 120 mg/dL.
Taken together, the data from the three trials showed that the AHCL-based system improved glycemic time-in-range with no increased risk for hypoglycemia, including in children and teenagers, with high patient-reported satisfaction. And specifically compared to the 670G, the AHCL-based system reverts to open-loop far less often because it only exits closed-loop mode when the sensor stops working or during sensor changes, but not during hyperglycemia even above 300 mg/dL.
Asked to comment, session moderator Timothy S. Bailey, MD, president and CEO of the AMCR Institute, Escondido, California, told Medscape Medical News: “Automated insulin delivery systems are getting better and better.”
“None of these devices is perfect, but they are a substantial improvement over what we’ve had ... They all take people from where they are now to better time-in-range, less time with hypoglycemia, and most important, they might make the quality of their lives better. That’s really underappreciated.”
One factor that has allowed for the improvements, Bailey said, is the recognition by regulatory bodies that the hybrid closed-loop devices are generally safer than current open-loop type 1 diabetes management so that fewer “safety” device features that interfere with tight glycemic control are necessary.
With first-generation closed-loop systems, “If a wide variety of conditions occur, users get kicked off [hybrid closed-loop mode]. Originally it was perceived by the regulatory agencies as a safety feature because they perceived the standard of care as safe. The new system was allowed to have fewer rules.”
Pivotal trial: Time-in-range improved, 96% say system easy to use
The goal of the AHCL system is to maximize the time-in-range of blood glucose between 70-180 mg/dL. Automated basal delivery of insulin is programmed to a set-point of 100 or 120 mg/dL, with dosing every 5 minutes.
The US pivotal trial was a single-arm, 16-center, in-home trial of 157 people with type 1 diabetes, including 39 adolescents aged 14-21 years and 118 adults aged 22-75 years. All had type 1 diabetes for at least 2 years, A1c levels below 10%, and had been using insulin pumps for at least 6 months, with or without CGMs.
After a 14-day run-in, they wore the systems with a 100 or 120 mg/dL set-point for 45 days, then switched to the other setpoint for another 45 days. Average A1c dropped from 7.5% to 7.0%, with the proportions having an A1c ≤ 7.0% increasing from 34% to 61%.
Overall time-in-range was 75% compared to 69% at baseline, with time below range (< 70 mg/dL) of 1.8%. Overnight time-in-range was 82%, with 1.5% below range. Time-in-range increased from 62% to 73% in the adolescents and from 71% to 75% in the adults.
There were no incidences of severe hypoglycemia or diabetic ketoacidosis, and no device-related serious adverse events.
Participants reported being in hybrid closed-loop, or auto-mode, 95% of the time, compared with 33% for those who had been previously using the 670G.
The number of AHCL exits was 1.3 per week, significantly less than with the 670G. Of those, 29% were user-initiated while the rest were implemented by the device, most often when the sensor wasn’t working.
In a study questionnaire, 96% reported that the system was easy to use.
AHCL vs 670G: Major improvements seen
Bergenstal presented data from the Fuzzy Logic Automated Insulin Regulation (FLAIR) study, funded by the National Institute of Diabetes and Digestive and Kidney Disease, comparing Medtronic’s AHCL-based system with the currently marketed 670G hybrid closed-loop, in 113 individuals with type 1 diabetes aged 14-29 years.
“This age group has traditionally been the most difficult group in which to optimize glucose management,” Bergenstal said.
FLAIR is believed to be the first-ever study comparing an investigational automated insulin delivery system with a commercially approved system, he noted. All participants used each automated insulin delivery system for 3 months in the randomized crossover trial.
The primary outcome, time spent above 180 mg/dL during the day combined with time below 54 mg/dL over 24 hours at baseline with the 670G and AHCL went from 42% to 37% to 34%, respectively, for the former and from 0.46% to 0.50% to 0.45%, respectively, for the latter.
The percentage time-in-range over 24 hours went from 57% at baseline to 67% with the AHCL versus 63% with the 670G. A1c levels dropped from 7.9% at baseline to 7.6% with the 670G and 7.4% with AHCL.
“Remember, these are the adolescents who are the toughest of the tough, yet there was a 10% increase in time-in-range ... this is very clinically significant,” Bergenstal said.
Even among 14 patients who had been using multiple daily injections without CGM prior to the study, a group often excluded from closed-loop studies, time-in-range improved from 45% at baseline to 63% with the 670G to 65% with AHCL.
“I’m making a plea not to exclude people just because they haven’t previously used technology,” Bergenstal said.
One patient who had dosed with extra insulin manually had a severe hypoglycemia event with AHCL. No patient had diabetic ketoacidosis.
The proportion of insulin given as auto-correction boluses was 36%, which is important as it means that the system was compensating for missed meal doses, a common phenomenon among teenagers, Bergenstal noted.
“There is still room for further improvement in glycemic control in this population of patients with type 1 diabetes, but AHCL represents a significant step forward,” he concluded.
New Zealand study: More data in youth show AHCL benefits
Unlike the US study populations of just teens aged 14 and older, and adults, the study data used for approval in the EU — from New Zealand — included a total of 60 patients with 20 children aged 7-15 years. It, too, was a 10-week randomized crossover clinical trial comparing the AHCL to a sensor-augmented pump system with an algorithm only for predictive low-glucose management (PLGM) and no adjustments for high blood glucose.
Time-in-range was 59% at baseline and 58% with PLGM, compared to 70.4% with AHCL, and most of the time-in-range improvement occurred at night. Time below 70 mg/dL dropped from 3.1% to 2.5% to 2.1%, respectively.
Similar to the US studies, participants spent 96% of the time in closed-loop mode with only 1.2 exits per week. On a questionnaire, 95% of patients agreed that the system was easy to use and 85% that the system improved their quality of life.
De Bock showed a slide with some quotes, including one from a parent saying, “We didn’t have to be fearful at night or have that thought when we opened her bedroom door in the morning that she might not be conscious,” and from a patient, “I forgot I had diabetes today.”
Bailey commented: “Of course these devices are not free. So, the challenge is how do we make them available, less expensive, and easy to use? We have our work cut out for us, but this is heartening data. Everything has gotten better but we’re not out of a job yet.”
Bailey has reported receiving research support from Abbott, Capillary Biomedical, Dexcom, Diasome, Eli Lilly, Kowa, Lexicon, Medtronic, Medtrum, Novo Nordisk, REMD, Sanofi, Senseonics, ViaCyte, vTv Therapeutics, Zealand Pharma, and consulting or speaking honoraria from Abbott, LifeScan, Novo Nordisk, Sanofi, and Medtronic. Bode has reported receiving consulting and speaker fees from Medtronic. Bergenstal has reported participating in clinical research, being an advisory board member, and/or serving as a consultant for Abbott Diabetes Care, Ascensia, CeQure, Dexcom, Eli Lilly, Hygieia, Senseonics, and United Healthcare. De Bock has reported receiving honoraria or expenses from Novo Nordisk, Sanofi, Pfizer, Medtronic, and Lilly, and research funds from Novo Nordisk and Medtronic.
This article first appeared on Medscape.com.
FROM ADA 2020
Half of type 1 diabetes patients with COVID-19 manage at home
New preliminary data from the T1D Exchange suggest that, although hyperglycemia and diabetic ketoacidosis (DKA) are common in people with type 1 diabetes who develop COVID-19, many are still able to manage the illness at home and overall mortality is relatively low.
The new findings – the first US data on individuals with type 1 diabetes and COVID-19 – were published online June 5 in Diabetes Care by Osagie A. Ebekozien, MD, vice president, quality improvement and population health at the T1D Exchange, and colleagues.
Two UK studies are the only prior ones to previously examine the topic.
The newly published study includes data as of May 5 on 64 individuals from a total of 64 US sites, including 15 T1D Exchange member clinics and an additional 49 endocrinology clinics from around the country. Since the paper was submitted, there are now 220 patients from 68 sites. Another publication with a more detailed analysis of risk factors and adjustment for confounders is planned for later this year.
Some of the findings from the preliminary data have shifted, but many aspects remain consistent, Ebekozien told Medscape Medical News.
“One thing still very true, even with the unpublished findings, is the influence of A1c and glycemic management. ...With higher A1c levels, we’re seeing more COVID-19 hospitalizations and worse outcomes,” he said.
And as has been generally reported for COVID-19, high body mass index was a major risk factor in the preliminary dataset – and remains so.
There were two deaths in the preliminary report, both individuals with comorbidities in addition to type 1 diabetes, Ebekozien said. There have been a few more deaths in the larger dataset, but the mortality rate remains relatively low.
Interestingly, females predominate in both cohorts. That may be a reporting phenomenon, another factor that is being analyzed.
Hyperglycemia Remains a Major Risk Factor
The study is specifically being conducted by the T1D Exchange’s Quality Improvement Collaborative, which Ebekozien heads.
Data were obtained for 33 patients with type 1 diabetes who tested positive for COVID-19, and another 31 who were classified as “COVID-19–like” because they had symptoms consistent with COVID-19, as identified by the Centers for Disease Control and Prevention, but hadn’t been tested for the virus.
For all 64 patients, the mean age was 20.9 years and two thirds (65.6%) were aged 18 or younger. A higher proportion of the COVID-19–like patients were pediatric than the confirmed cases. The larger dataset includes more adult patients, Ebekozien told Medscape Medical News.
Overall, 60.9% of patients were female. Nearly half were white, a quarter Hispanic, and 18.8% black. More confirmed COVID-19 cases were black compared with suspected cases (30.3% vs 6.5%).
Median A1c for the overall group (including suspected COVID-19 cases) was 8.0%, but it was 8.5% among confirmed cases. Overall, six patients (9.8%) presented with new-onset type 1 diabetes after they developed COVID-19.
Hyperglycemia was present in half (32) of patients overall. DKA occurred in 19 people (30.2%): 15 of the confirmed COVID-19 cases (45.5%) versus just 4 (13.3%) of the COVID-19–like cases. Nausea was reported in 30.2% of patients overall.
Other symptoms were typical of COVID-19, including fever (41.3%), dry cough (38.1%), and shortness of breath (27.0%). Loss of taste and smell was less common, at just 9.5% overall.
Obesity was present in 39.7% of patients overall, with similar proportions in the confirmed and suspected COVID-19 groups. Hypertension and/or cardiovascular disease were present in 14.3% of patients overall, and the rate was similar between the two subgroups.
One of the two patients who died was a 79-year-old man who had hypertension and a prior stroke in addition to type 1 diabetes. The other was a 19-year-old woman with a history of asthma who developed a pulmonary embolism during the onset of COVID-19. Neither had DKA.
Even in Type 1 Diabetes, COVID-19 Can Be Managed at Home
Overall, 34.9% of patients were able to manage COVID-19 entirely at home, with 27.3% of the confirmed and 43.3% of the suspected cases able to do so.
At the other extreme, 22.2% of patients overall were admitted to the intensive care unit; 30.3% of the confirmed versus 13.3% of suspected cases.
Including the small proportion of patients sent home after being seen in emergency or urgent care, overall roughly half were not admitted to hospital.
“Interestingly, even in this preliminary study, half were managed at home via telemedicine with an endocrinologist and infectious disease specialist. ... I think it continues to be a case-by-case clinical decision between the patient and their provider,” Ebekozien said.
“But, we’re seeing a good number of patients who are managed at home and the symptoms resolve in a week or two, and the illness runs its course, and they don’t have to even be seen,” he added.
The research team is also collecting data on barriers to remote care, including challenges with telemedicine and how frontline providers are navigating them.
“Those are all things that our future paper will be able to shed more light on,” he explained.
Endocrinologists around the country are invited to report cases of COVID-19 in patients with type 1 diabetes to the T1D Exchange by emailing [email protected].
And in fact, Ebekozien also requested that clinicians with a large type 1 diabetes population also report if they’ve had no COVID-19 cases.
“Even if they haven’t had a case, that’s very useful information for us to know. One of the things we want to calculate down the line is the incidence ratio. Not all participating sites have had a case.”
Endocrinologists from all the participating sites have formed a dedicated community that meets regularly via webinars to share information, he noted. “It’s been a very selfless effort to work collaboratively as a community to quickly answer critical questions.”
The Helmsley Charitable Trust funds the T1D Exchange Quality Improvement Collaborative. The T1D Exchange received financial support for this study from Abbott Diabetes, Dexcom, JDRF, Insulet Corporation, Lilly, Medtronic, and Tandem Diabetes Care. No other relevant financial relationships were reported.
This article first appeared on Medscape.com.
New preliminary data from the T1D Exchange suggest that, although hyperglycemia and diabetic ketoacidosis (DKA) are common in people with type 1 diabetes who develop COVID-19, many are still able to manage the illness at home and overall mortality is relatively low.
The new findings – the first US data on individuals with type 1 diabetes and COVID-19 – were published online June 5 in Diabetes Care by Osagie A. Ebekozien, MD, vice president, quality improvement and population health at the T1D Exchange, and colleagues.
Two UK studies are the only prior ones to previously examine the topic.
The newly published study includes data as of May 5 on 64 individuals from a total of 64 US sites, including 15 T1D Exchange member clinics and an additional 49 endocrinology clinics from around the country. Since the paper was submitted, there are now 220 patients from 68 sites. Another publication with a more detailed analysis of risk factors and adjustment for confounders is planned for later this year.
Some of the findings from the preliminary data have shifted, but many aspects remain consistent, Ebekozien told Medscape Medical News.
“One thing still very true, even with the unpublished findings, is the influence of A1c and glycemic management. ...With higher A1c levels, we’re seeing more COVID-19 hospitalizations and worse outcomes,” he said.
And as has been generally reported for COVID-19, high body mass index was a major risk factor in the preliminary dataset – and remains so.
There were two deaths in the preliminary report, both individuals with comorbidities in addition to type 1 diabetes, Ebekozien said. There have been a few more deaths in the larger dataset, but the mortality rate remains relatively low.
Interestingly, females predominate in both cohorts. That may be a reporting phenomenon, another factor that is being analyzed.
Hyperglycemia Remains a Major Risk Factor
The study is specifically being conducted by the T1D Exchange’s Quality Improvement Collaborative, which Ebekozien heads.
Data were obtained for 33 patients with type 1 diabetes who tested positive for COVID-19, and another 31 who were classified as “COVID-19–like” because they had symptoms consistent with COVID-19, as identified by the Centers for Disease Control and Prevention, but hadn’t been tested for the virus.
For all 64 patients, the mean age was 20.9 years and two thirds (65.6%) were aged 18 or younger. A higher proportion of the COVID-19–like patients were pediatric than the confirmed cases. The larger dataset includes more adult patients, Ebekozien told Medscape Medical News.
Overall, 60.9% of patients were female. Nearly half were white, a quarter Hispanic, and 18.8% black. More confirmed COVID-19 cases were black compared with suspected cases (30.3% vs 6.5%).
Median A1c for the overall group (including suspected COVID-19 cases) was 8.0%, but it was 8.5% among confirmed cases. Overall, six patients (9.8%) presented with new-onset type 1 diabetes after they developed COVID-19.
Hyperglycemia was present in half (32) of patients overall. DKA occurred in 19 people (30.2%): 15 of the confirmed COVID-19 cases (45.5%) versus just 4 (13.3%) of the COVID-19–like cases. Nausea was reported in 30.2% of patients overall.
Other symptoms were typical of COVID-19, including fever (41.3%), dry cough (38.1%), and shortness of breath (27.0%). Loss of taste and smell was less common, at just 9.5% overall.
Obesity was present in 39.7% of patients overall, with similar proportions in the confirmed and suspected COVID-19 groups. Hypertension and/or cardiovascular disease were present in 14.3% of patients overall, and the rate was similar between the two subgroups.
One of the two patients who died was a 79-year-old man who had hypertension and a prior stroke in addition to type 1 diabetes. The other was a 19-year-old woman with a history of asthma who developed a pulmonary embolism during the onset of COVID-19. Neither had DKA.
Even in Type 1 Diabetes, COVID-19 Can Be Managed at Home
Overall, 34.9% of patients were able to manage COVID-19 entirely at home, with 27.3% of the confirmed and 43.3% of the suspected cases able to do so.
At the other extreme, 22.2% of patients overall were admitted to the intensive care unit; 30.3% of the confirmed versus 13.3% of suspected cases.
Including the small proportion of patients sent home after being seen in emergency or urgent care, overall roughly half were not admitted to hospital.
“Interestingly, even in this preliminary study, half were managed at home via telemedicine with an endocrinologist and infectious disease specialist. ... I think it continues to be a case-by-case clinical decision between the patient and their provider,” Ebekozien said.
“But, we’re seeing a good number of patients who are managed at home and the symptoms resolve in a week or two, and the illness runs its course, and they don’t have to even be seen,” he added.
The research team is also collecting data on barriers to remote care, including challenges with telemedicine and how frontline providers are navigating them.
“Those are all things that our future paper will be able to shed more light on,” he explained.
Endocrinologists around the country are invited to report cases of COVID-19 in patients with type 1 diabetes to the T1D Exchange by emailing [email protected].
And in fact, Ebekozien also requested that clinicians with a large type 1 diabetes population also report if they’ve had no COVID-19 cases.
“Even if they haven’t had a case, that’s very useful information for us to know. One of the things we want to calculate down the line is the incidence ratio. Not all participating sites have had a case.”
Endocrinologists from all the participating sites have formed a dedicated community that meets regularly via webinars to share information, he noted. “It’s been a very selfless effort to work collaboratively as a community to quickly answer critical questions.”
The Helmsley Charitable Trust funds the T1D Exchange Quality Improvement Collaborative. The T1D Exchange received financial support for this study from Abbott Diabetes, Dexcom, JDRF, Insulet Corporation, Lilly, Medtronic, and Tandem Diabetes Care. No other relevant financial relationships were reported.
This article first appeared on Medscape.com.
New preliminary data from the T1D Exchange suggest that, although hyperglycemia and diabetic ketoacidosis (DKA) are common in people with type 1 diabetes who develop COVID-19, many are still able to manage the illness at home and overall mortality is relatively low.
The new findings – the first US data on individuals with type 1 diabetes and COVID-19 – were published online June 5 in Diabetes Care by Osagie A. Ebekozien, MD, vice president, quality improvement and population health at the T1D Exchange, and colleagues.
Two UK studies are the only prior ones to previously examine the topic.
The newly published study includes data as of May 5 on 64 individuals from a total of 64 US sites, including 15 T1D Exchange member clinics and an additional 49 endocrinology clinics from around the country. Since the paper was submitted, there are now 220 patients from 68 sites. Another publication with a more detailed analysis of risk factors and adjustment for confounders is planned for later this year.
Some of the findings from the preliminary data have shifted, but many aspects remain consistent, Ebekozien told Medscape Medical News.
“One thing still very true, even with the unpublished findings, is the influence of A1c and glycemic management. ...With higher A1c levels, we’re seeing more COVID-19 hospitalizations and worse outcomes,” he said.
And as has been generally reported for COVID-19, high body mass index was a major risk factor in the preliminary dataset – and remains so.
There were two deaths in the preliminary report, both individuals with comorbidities in addition to type 1 diabetes, Ebekozien said. There have been a few more deaths in the larger dataset, but the mortality rate remains relatively low.
Interestingly, females predominate in both cohorts. That may be a reporting phenomenon, another factor that is being analyzed.
Hyperglycemia Remains a Major Risk Factor
The study is specifically being conducted by the T1D Exchange’s Quality Improvement Collaborative, which Ebekozien heads.
Data were obtained for 33 patients with type 1 diabetes who tested positive for COVID-19, and another 31 who were classified as “COVID-19–like” because they had symptoms consistent with COVID-19, as identified by the Centers for Disease Control and Prevention, but hadn’t been tested for the virus.
For all 64 patients, the mean age was 20.9 years and two thirds (65.6%) were aged 18 or younger. A higher proportion of the COVID-19–like patients were pediatric than the confirmed cases. The larger dataset includes more adult patients, Ebekozien told Medscape Medical News.
Overall, 60.9% of patients were female. Nearly half were white, a quarter Hispanic, and 18.8% black. More confirmed COVID-19 cases were black compared with suspected cases (30.3% vs 6.5%).
Median A1c for the overall group (including suspected COVID-19 cases) was 8.0%, but it was 8.5% among confirmed cases. Overall, six patients (9.8%) presented with new-onset type 1 diabetes after they developed COVID-19.
Hyperglycemia was present in half (32) of patients overall. DKA occurred in 19 people (30.2%): 15 of the confirmed COVID-19 cases (45.5%) versus just 4 (13.3%) of the COVID-19–like cases. Nausea was reported in 30.2% of patients overall.
Other symptoms were typical of COVID-19, including fever (41.3%), dry cough (38.1%), and shortness of breath (27.0%). Loss of taste and smell was less common, at just 9.5% overall.
Obesity was present in 39.7% of patients overall, with similar proportions in the confirmed and suspected COVID-19 groups. Hypertension and/or cardiovascular disease were present in 14.3% of patients overall, and the rate was similar between the two subgroups.
One of the two patients who died was a 79-year-old man who had hypertension and a prior stroke in addition to type 1 diabetes. The other was a 19-year-old woman with a history of asthma who developed a pulmonary embolism during the onset of COVID-19. Neither had DKA.
Even in Type 1 Diabetes, COVID-19 Can Be Managed at Home
Overall, 34.9% of patients were able to manage COVID-19 entirely at home, with 27.3% of the confirmed and 43.3% of the suspected cases able to do so.
At the other extreme, 22.2% of patients overall were admitted to the intensive care unit; 30.3% of the confirmed versus 13.3% of suspected cases.
Including the small proportion of patients sent home after being seen in emergency or urgent care, overall roughly half were not admitted to hospital.
“Interestingly, even in this preliminary study, half were managed at home via telemedicine with an endocrinologist and infectious disease specialist. ... I think it continues to be a case-by-case clinical decision between the patient and their provider,” Ebekozien said.
“But, we’re seeing a good number of patients who are managed at home and the symptoms resolve in a week or two, and the illness runs its course, and they don’t have to even be seen,” he added.
The research team is also collecting data on barriers to remote care, including challenges with telemedicine and how frontline providers are navigating them.
“Those are all things that our future paper will be able to shed more light on,” he explained.
Endocrinologists around the country are invited to report cases of COVID-19 in patients with type 1 diabetes to the T1D Exchange by emailing [email protected].
And in fact, Ebekozien also requested that clinicians with a large type 1 diabetes population also report if they’ve had no COVID-19 cases.
“Even if they haven’t had a case, that’s very useful information for us to know. One of the things we want to calculate down the line is the incidence ratio. Not all participating sites have had a case.”
Endocrinologists from all the participating sites have formed a dedicated community that meets regularly via webinars to share information, he noted. “It’s been a very selfless effort to work collaboratively as a community to quickly answer critical questions.”
The Helmsley Charitable Trust funds the T1D Exchange Quality Improvement Collaborative. The T1D Exchange received financial support for this study from Abbott Diabetes, Dexcom, JDRF, Insulet Corporation, Lilly, Medtronic, and Tandem Diabetes Care. No other relevant financial relationships were reported.
This article first appeared on Medscape.com.
Long-acting insulin analogue approved for type 1 and type 2 diabetes
the Food and Drug Administration announced June 11.
“Long-acting insulin products like insulin glargine play an important role in the treatment of types 1 and 2 diabetes mellitus,” Patrick Archdeacon, MD, acting associate director for therapeutics in the FDA’s Division of Diabetes, Lipid Disorders, and Obesity, said in a written statement via email.
Semglee will be marketed by Mylan Pharmaceuticals and will be available in a multidose 10-mL vial or a single-patient-use 3-mL prefilled pen.
The approval was based primarily on two randomized, confirmatory clinical trials called INSTRIDE1 and INSTRIDE 2, according to a release by Mylan and Biocon Biologic. They compared Semglee (MYL-1501D) to branded insulin glargine (Lantus) in adults and children for 1 year and found no treatment difference.
The FDA noted that, for patients with type 1 diabetes, Semglee must be used along with a short-acting insulin. The recommended starting dose is approximately one-third of the total daily insulin requirement. For those with type 2 diabetes, the starting dose is 0.2 units/kg or up to 10 units once daily, according to the prescribing information.
Semglee is not recommended for treating diabetic ketoacidosis and is contraindicated during episodes of hypoglycemia.
“Today’s approval provides patients with an additional safe and effective treatment option and also expands the number of products that are available to serve as a reference product for a proposed insulin glargine biosimilar or interchangeable biosimilar product now that the biosimilar pathway is available for insulin products following the statutory transition earlier this year,” Dr. Archdeacon said.
the Food and Drug Administration announced June 11.
“Long-acting insulin products like insulin glargine play an important role in the treatment of types 1 and 2 diabetes mellitus,” Patrick Archdeacon, MD, acting associate director for therapeutics in the FDA’s Division of Diabetes, Lipid Disorders, and Obesity, said in a written statement via email.
Semglee will be marketed by Mylan Pharmaceuticals and will be available in a multidose 10-mL vial or a single-patient-use 3-mL prefilled pen.
The approval was based primarily on two randomized, confirmatory clinical trials called INSTRIDE1 and INSTRIDE 2, according to a release by Mylan and Biocon Biologic. They compared Semglee (MYL-1501D) to branded insulin glargine (Lantus) in adults and children for 1 year and found no treatment difference.
The FDA noted that, for patients with type 1 diabetes, Semglee must be used along with a short-acting insulin. The recommended starting dose is approximately one-third of the total daily insulin requirement. For those with type 2 diabetes, the starting dose is 0.2 units/kg or up to 10 units once daily, according to the prescribing information.
Semglee is not recommended for treating diabetic ketoacidosis and is contraindicated during episodes of hypoglycemia.
“Today’s approval provides patients with an additional safe and effective treatment option and also expands the number of products that are available to serve as a reference product for a proposed insulin glargine biosimilar or interchangeable biosimilar product now that the biosimilar pathway is available for insulin products following the statutory transition earlier this year,” Dr. Archdeacon said.
the Food and Drug Administration announced June 11.
“Long-acting insulin products like insulin glargine play an important role in the treatment of types 1 and 2 diabetes mellitus,” Patrick Archdeacon, MD, acting associate director for therapeutics in the FDA’s Division of Diabetes, Lipid Disorders, and Obesity, said in a written statement via email.
Semglee will be marketed by Mylan Pharmaceuticals and will be available in a multidose 10-mL vial or a single-patient-use 3-mL prefilled pen.
The approval was based primarily on two randomized, confirmatory clinical trials called INSTRIDE1 and INSTRIDE 2, according to a release by Mylan and Biocon Biologic. They compared Semglee (MYL-1501D) to branded insulin glargine (Lantus) in adults and children for 1 year and found no treatment difference.
The FDA noted that, for patients with type 1 diabetes, Semglee must be used along with a short-acting insulin. The recommended starting dose is approximately one-third of the total daily insulin requirement. For those with type 2 diabetes, the starting dose is 0.2 units/kg or up to 10 units once daily, according to the prescribing information.
Semglee is not recommended for treating diabetic ketoacidosis and is contraindicated during episodes of hypoglycemia.
“Today’s approval provides patients with an additional safe and effective treatment option and also expands the number of products that are available to serve as a reference product for a proposed insulin glargine biosimilar or interchangeable biosimilar product now that the biosimilar pathway is available for insulin products following the statutory transition earlier this year,” Dr. Archdeacon said.
Virtual ADA Scientific Sessions to offer full program
The American Diabetes Association’s 80th Scientific Sessions will forge ahead virtually this year in the face of the COVID-19 pandemic, with nearly all of its originally scheduled content to be presented online.
The meeting will take place online June 12-16, the same days it was slated to occur in Chicago and at the same times. All presentations were recorded in advance, but participants will be able to ask real-time questions during some sessions. Registered attendees – who paid a reduced fee – will have access to the online content for 90 days afterward.
ADA announced the shift in plans on April 3, after Chicago’s McCormick Place convention center became unavailable due to the COVID-19 pandemic. While some major medical meetings had to be canceled entirely or trimmed down online, “This is one of the international meetings that has had more time to really get ready to plan such a virtual session,” association co-president Robert H. Eckel, MD, told Medscape Medical News.
This year’s program features fewer blockbuster randomized clinical trials than in years past.
But it does offer a huge amount of clinical research focused on both type 1 and type 2 diabetes, children with diabetes, gestational diabetes, and much more. Also included are deep dives into optimal clinical translation of findings from previous cardiovascular outcomes trials (CVOTs).
Noteworthy sessions include four new automated insulin delivery system trials on Friday, new diabetes-specific data from the DAPA-HF trial on Saturday, and a debate on Sunday about the future of metformin as first-line therapy for people with established heart disease or at high risk.
And on Tuesday morning, full results from the CVOT VERTIS-CV, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin (Steglatro, Merck), will be reported.
Also presented on Tuesday will be the first cardiovascular and cancer outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS).
The online content will cover roughly 90% of what was originally scheduled, meeting planning committee chair Jose C. Florez, MD, PhD, told Medscape Medical News.
There is no session officially addressing COVID-19, he said, because the topics were already finalized by February, but “I’m sure it will be discussed in informal exchanges ... the data are just coming out,” he said.
Florez also called attention to two symposia addressing the other major topic dominating today’s news: racial disparities. One on Friday will address that topic with regard to maternal/fetal health, and another on Monday will cover disparities in diabetes care generally.
“Both because of COVID-19 and how it has affected people with diabetes, and within that, disadvantaged people, more aggressively, and in the current context of how racism is coming to the surface, these two sessions will become very, very pertinent,” he said.
Putting the Treatment Pieces Together in Type 2 Diabetes
The Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS-CV) session will include the major cardiovascular, metabolic, renal, and safety outcomes for that drug, along with a meta-analysis of outcomes from trials of several different SGLT2 inhibitors.
All eyes will be on the VERTIS-CV presentation because ertugliflozin broke ranks with the other drugs in this class and failed to produce statistically significant drops in the relevant endpoints, as detailed in top-line data issued by the company in April.
And the provocatively titled session, “DAPA-HF Update: Have We Lost SGLT2 inhibitors to Cardiologists?!” will include a review of the trial’s main findings presented at the European Society of Cardiology meeting in September 2019, and published a few weeks later in the New England Journal of Medicine, along with new data on patient-centered and metabolic outcomes, and diabetes prevention. An independent commentator will presumably address the session title’s question.
Eckel, who has been working to establish a new cardiometabolic medicine subspecialty, commented: “I think we have not lost it, but I think SGLT2 inhibitors are a perfect example of why we need physicians trained in this overlap of diabetes medicine and cardiology.”
And, he said, we may be coming to the end of the CVOTs trial phenomenon.
“I think unless there’s a whole new class of drugs developed, we may be done with CVOTs for dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists. We’ve learned a lot, and I’m not sure we need more other than mechanistic studies ... I don’t think we really know yet how SGLT2 inhibitors or GLP-1 agonists work,” Eckel said.
Metformin, on the other hand, has not been subject to a CVOT because it has been available as a generic since long before the US Food and Drug Administration mandated the CVOTs for new drugs for type 2 diabetes in 2008.
Such a trial is unlikely to be conducted at this point, but the new DPPOS data might actually come close, Florez noted.
The DPPOS is the observational follow-up of the landmark randomized DPP trial, which found that intensive lifestyle intervention and metformin reduced progression from prediabetes to type 2 diabetes.
Numerous additional outcomes have been reported over the years, but this will be the first-ever reporting of DPPOS data on both hard cardiovascular events and cancer incidence in people who have been continuously taking metformin for more than 20 years.
“There’s a lot of interest in whether metformin has an effect on cardiovascular events and cancer ... I think that’s going to be a very interesting session,” Florez said, noting that “short of a randomized clinical trial, which it’s hard to imagine would come to be, this is really, really good.”
Also examining metformin will be a debate on Sunday, “Should Metformin Be Considered First-Line Therapy for Individuals with Type 2 Diabetes With Established Arteriosclerotic Cardiovascular Disease (ASCVD) or at High Risk for ASCVD?”
And on Saturday, a debate will address another old-guard diabetes drug class, asking: “Is There a Current Place for Sulfonylureas in the Treatment of Type 2 Diabetes?”
Overall, Florez said, meeting attendees will come away with “a more clear understanding of the placement of SGLT2 inhibitors and GLP-1 agonists in the type 2 diabetes treatment algorithm.”
“What are the settings in which these [newer] drugs ought to be used, compared to the old-timers like metformin and sulfonylureas? One thing is having the trials, but the other is figuring out how you interpret these in deciding what happens at the point of care.”
Two more future-looking type 2 diabetes symposia of potential interest to clinicians are “Unraveling the Heterogeneity in Type 2 Diabetes” on Sunday and “Perspectives on the Future of Precision Diabetes Medicine — A Joint ADA/EASD Symposium” on Monday.
Type 1 Diabetes, Technology, and Kids
A symposium on Friday will feature four new clinical trials of automated insulin delivery systems for people with type 1 diabetes, the “US Advanced Hybrid Closed-Loop (AHCL) Pivotal Safety Study, FLAIR — An NIDDK-Sponsored International, Multi-site Randomized Crossover Trial of AHCL vs 670G,” the New Zealand AHCL randomized crossover trial, and the Horizon Automated Glucose Control System pre-pivotal trial data.
“Closed-loop devices are getting a lot of traction ... These trials will continue to advance the notion that these devices will narrow the glycemic range, prevent hypoglycemia, and improve quality of life because people don’t have to pay as much attention mentally to the management of the diabetes,” Florez said.
He added that although these trials “have been in the works for a while and they’re not big surprises, they continue to build a body of evidence suggesting that these devices will be part of our armamentarium in the very near future.”
And on Saturday, a debate will address the somewhat controversial question of whether continuous glucose monitoring in type 2 diabetes is worth the cost.
There will also be plenty of pediatric diabetes material presented this year, too.
On Sunday, there will be new insights from the Restoring Insulin Secretion (RISE) study, which examines prediabetes and type 2 diabetes in youth, and on Monday, 20-year data from the SEARCH for Diabetes in Youth Study will be reported.
And on Monday, the most recent findings from The Environmental Determinants of Diabetes in the Young (TEDDY) study of environmental triggers of type 1 diabetes will be presented.
All-Virtual Meeting: Pros and Cons
The all-virtual meeting format will have pluses and minuses, Eckel predicts.
Advantages include the fact that attendees don’t have to physically run from room to room or make difficult decisions about conflicting sessions.
“The fact that this meeting will be taking place in reality in terms of the timing of sessions, one can transition from one room to another in a matter of seconds if you want to,” he noted.
However, he observed, “a lot of interesting things happen in the hallways at meetings. Colleagues from around the world get together and knock heads about their ongoing research and potential collaborations can be formulated.
“Opportunities to engage with one another beyond the formality of the meeting is going to be lost to some extent.”
What’s more, the sessions will all be in Central US (Chicago) time, “So if you live in Thailand, the session may be occurring at a time when you’re in bed. If you want to see it live, then you’ve got to get up. Then you can ask a question.”
On the other hand, since all the content will be available online for 90 days, “if you want to stay in bed and you live in Thailand, you can get up a week from now during the day and log into a session you may have missed.”
Indeed, Florez said, “One silver lining of this virtual conference is that we’ve lowered the barriers for people to attend. It’s much more global. We’ve had an amazing influx of new registrants who were not planning on coming and were not registered for the original meeting and have registered since [more than 10,000 at the time of writing], and they continue to pile in.”
“We plan to reach people we haven’t reached before. The big question for ADA moving forward will be how much this can become a permanent feature, where even if we do it in person in the future, maybe we offer at least some virtual options so that our reach can go farther.”
Eckel has reported sitting on the scientific advisory board for a Kowa Company trial of pemafibrate and on an advisory board for Novo Nordisk. Florez has reported being a speaker for Novo Nordisk and receiving an honorarium from ADA for chairing the conference planning committee.
This article originally appeared on Medscape.com.
The American Diabetes Association’s 80th Scientific Sessions will forge ahead virtually this year in the face of the COVID-19 pandemic, with nearly all of its originally scheduled content to be presented online.
The meeting will take place online June 12-16, the same days it was slated to occur in Chicago and at the same times. All presentations were recorded in advance, but participants will be able to ask real-time questions during some sessions. Registered attendees – who paid a reduced fee – will have access to the online content for 90 days afterward.
ADA announced the shift in plans on April 3, after Chicago’s McCormick Place convention center became unavailable due to the COVID-19 pandemic. While some major medical meetings had to be canceled entirely or trimmed down online, “This is one of the international meetings that has had more time to really get ready to plan such a virtual session,” association co-president Robert H. Eckel, MD, told Medscape Medical News.
This year’s program features fewer blockbuster randomized clinical trials than in years past.
But it does offer a huge amount of clinical research focused on both type 1 and type 2 diabetes, children with diabetes, gestational diabetes, and much more. Also included are deep dives into optimal clinical translation of findings from previous cardiovascular outcomes trials (CVOTs).
Noteworthy sessions include four new automated insulin delivery system trials on Friday, new diabetes-specific data from the DAPA-HF trial on Saturday, and a debate on Sunday about the future of metformin as first-line therapy for people with established heart disease or at high risk.
And on Tuesday morning, full results from the CVOT VERTIS-CV, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin (Steglatro, Merck), will be reported.
Also presented on Tuesday will be the first cardiovascular and cancer outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS).
The online content will cover roughly 90% of what was originally scheduled, meeting planning committee chair Jose C. Florez, MD, PhD, told Medscape Medical News.
There is no session officially addressing COVID-19, he said, because the topics were already finalized by February, but “I’m sure it will be discussed in informal exchanges ... the data are just coming out,” he said.
Florez also called attention to two symposia addressing the other major topic dominating today’s news: racial disparities. One on Friday will address that topic with regard to maternal/fetal health, and another on Monday will cover disparities in diabetes care generally.
“Both because of COVID-19 and how it has affected people with diabetes, and within that, disadvantaged people, more aggressively, and in the current context of how racism is coming to the surface, these two sessions will become very, very pertinent,” he said.
Putting the Treatment Pieces Together in Type 2 Diabetes
The Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS-CV) session will include the major cardiovascular, metabolic, renal, and safety outcomes for that drug, along with a meta-analysis of outcomes from trials of several different SGLT2 inhibitors.
All eyes will be on the VERTIS-CV presentation because ertugliflozin broke ranks with the other drugs in this class and failed to produce statistically significant drops in the relevant endpoints, as detailed in top-line data issued by the company in April.
And the provocatively titled session, “DAPA-HF Update: Have We Lost SGLT2 inhibitors to Cardiologists?!” will include a review of the trial’s main findings presented at the European Society of Cardiology meeting in September 2019, and published a few weeks later in the New England Journal of Medicine, along with new data on patient-centered and metabolic outcomes, and diabetes prevention. An independent commentator will presumably address the session title’s question.
Eckel, who has been working to establish a new cardiometabolic medicine subspecialty, commented: “I think we have not lost it, but I think SGLT2 inhibitors are a perfect example of why we need physicians trained in this overlap of diabetes medicine and cardiology.”
And, he said, we may be coming to the end of the CVOTs trial phenomenon.
“I think unless there’s a whole new class of drugs developed, we may be done with CVOTs for dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists. We’ve learned a lot, and I’m not sure we need more other than mechanistic studies ... I don’t think we really know yet how SGLT2 inhibitors or GLP-1 agonists work,” Eckel said.
Metformin, on the other hand, has not been subject to a CVOT because it has been available as a generic since long before the US Food and Drug Administration mandated the CVOTs for new drugs for type 2 diabetes in 2008.
Such a trial is unlikely to be conducted at this point, but the new DPPOS data might actually come close, Florez noted.
The DPPOS is the observational follow-up of the landmark randomized DPP trial, which found that intensive lifestyle intervention and metformin reduced progression from prediabetes to type 2 diabetes.
Numerous additional outcomes have been reported over the years, but this will be the first-ever reporting of DPPOS data on both hard cardiovascular events and cancer incidence in people who have been continuously taking metformin for more than 20 years.
“There’s a lot of interest in whether metformin has an effect on cardiovascular events and cancer ... I think that’s going to be a very interesting session,” Florez said, noting that “short of a randomized clinical trial, which it’s hard to imagine would come to be, this is really, really good.”
Also examining metformin will be a debate on Sunday, “Should Metformin Be Considered First-Line Therapy for Individuals with Type 2 Diabetes With Established Arteriosclerotic Cardiovascular Disease (ASCVD) or at High Risk for ASCVD?”
And on Saturday, a debate will address another old-guard diabetes drug class, asking: “Is There a Current Place for Sulfonylureas in the Treatment of Type 2 Diabetes?”
Overall, Florez said, meeting attendees will come away with “a more clear understanding of the placement of SGLT2 inhibitors and GLP-1 agonists in the type 2 diabetes treatment algorithm.”
“What are the settings in which these [newer] drugs ought to be used, compared to the old-timers like metformin and sulfonylureas? One thing is having the trials, but the other is figuring out how you interpret these in deciding what happens at the point of care.”
Two more future-looking type 2 diabetes symposia of potential interest to clinicians are “Unraveling the Heterogeneity in Type 2 Diabetes” on Sunday and “Perspectives on the Future of Precision Diabetes Medicine — A Joint ADA/EASD Symposium” on Monday.
Type 1 Diabetes, Technology, and Kids
A symposium on Friday will feature four new clinical trials of automated insulin delivery systems for people with type 1 diabetes, the “US Advanced Hybrid Closed-Loop (AHCL) Pivotal Safety Study, FLAIR — An NIDDK-Sponsored International, Multi-site Randomized Crossover Trial of AHCL vs 670G,” the New Zealand AHCL randomized crossover trial, and the Horizon Automated Glucose Control System pre-pivotal trial data.
“Closed-loop devices are getting a lot of traction ... These trials will continue to advance the notion that these devices will narrow the glycemic range, prevent hypoglycemia, and improve quality of life because people don’t have to pay as much attention mentally to the management of the diabetes,” Florez said.
He added that although these trials “have been in the works for a while and they’re not big surprises, they continue to build a body of evidence suggesting that these devices will be part of our armamentarium in the very near future.”
And on Saturday, a debate will address the somewhat controversial question of whether continuous glucose monitoring in type 2 diabetes is worth the cost.
There will also be plenty of pediatric diabetes material presented this year, too.
On Sunday, there will be new insights from the Restoring Insulin Secretion (RISE) study, which examines prediabetes and type 2 diabetes in youth, and on Monday, 20-year data from the SEARCH for Diabetes in Youth Study will be reported.
And on Monday, the most recent findings from The Environmental Determinants of Diabetes in the Young (TEDDY) study of environmental triggers of type 1 diabetes will be presented.
All-Virtual Meeting: Pros and Cons
The all-virtual meeting format will have pluses and minuses, Eckel predicts.
Advantages include the fact that attendees don’t have to physically run from room to room or make difficult decisions about conflicting sessions.
“The fact that this meeting will be taking place in reality in terms of the timing of sessions, one can transition from one room to another in a matter of seconds if you want to,” he noted.
However, he observed, “a lot of interesting things happen in the hallways at meetings. Colleagues from around the world get together and knock heads about their ongoing research and potential collaborations can be formulated.
“Opportunities to engage with one another beyond the formality of the meeting is going to be lost to some extent.”
What’s more, the sessions will all be in Central US (Chicago) time, “So if you live in Thailand, the session may be occurring at a time when you’re in bed. If you want to see it live, then you’ve got to get up. Then you can ask a question.”
On the other hand, since all the content will be available online for 90 days, “if you want to stay in bed and you live in Thailand, you can get up a week from now during the day and log into a session you may have missed.”
Indeed, Florez said, “One silver lining of this virtual conference is that we’ve lowered the barriers for people to attend. It’s much more global. We’ve had an amazing influx of new registrants who were not planning on coming and were not registered for the original meeting and have registered since [more than 10,000 at the time of writing], and they continue to pile in.”
“We plan to reach people we haven’t reached before. The big question for ADA moving forward will be how much this can become a permanent feature, where even if we do it in person in the future, maybe we offer at least some virtual options so that our reach can go farther.”
Eckel has reported sitting on the scientific advisory board for a Kowa Company trial of pemafibrate and on an advisory board for Novo Nordisk. Florez has reported being a speaker for Novo Nordisk and receiving an honorarium from ADA for chairing the conference planning committee.
This article originally appeared on Medscape.com.
The American Diabetes Association’s 80th Scientific Sessions will forge ahead virtually this year in the face of the COVID-19 pandemic, with nearly all of its originally scheduled content to be presented online.
The meeting will take place online June 12-16, the same days it was slated to occur in Chicago and at the same times. All presentations were recorded in advance, but participants will be able to ask real-time questions during some sessions. Registered attendees – who paid a reduced fee – will have access to the online content for 90 days afterward.
ADA announced the shift in plans on April 3, after Chicago’s McCormick Place convention center became unavailable due to the COVID-19 pandemic. While some major medical meetings had to be canceled entirely or trimmed down online, “This is one of the international meetings that has had more time to really get ready to plan such a virtual session,” association co-president Robert H. Eckel, MD, told Medscape Medical News.
This year’s program features fewer blockbuster randomized clinical trials than in years past.
But it does offer a huge amount of clinical research focused on both type 1 and type 2 diabetes, children with diabetes, gestational diabetes, and much more. Also included are deep dives into optimal clinical translation of findings from previous cardiovascular outcomes trials (CVOTs).
Noteworthy sessions include four new automated insulin delivery system trials on Friday, new diabetes-specific data from the DAPA-HF trial on Saturday, and a debate on Sunday about the future of metformin as first-line therapy for people with established heart disease or at high risk.
And on Tuesday morning, full results from the CVOT VERTIS-CV, with the sodium-glucose cotransporter 2 (SGLT2) inhibitor ertugliflozin (Steglatro, Merck), will be reported.
Also presented on Tuesday will be the first cardiovascular and cancer outcomes from the Diabetes Prevention Program Outcomes Study (DPPOS).
The online content will cover roughly 90% of what was originally scheduled, meeting planning committee chair Jose C. Florez, MD, PhD, told Medscape Medical News.
There is no session officially addressing COVID-19, he said, because the topics were already finalized by February, but “I’m sure it will be discussed in informal exchanges ... the data are just coming out,” he said.
Florez also called attention to two symposia addressing the other major topic dominating today’s news: racial disparities. One on Friday will address that topic with regard to maternal/fetal health, and another on Monday will cover disparities in diabetes care generally.
“Both because of COVID-19 and how it has affected people with diabetes, and within that, disadvantaged people, more aggressively, and in the current context of how racism is coming to the surface, these two sessions will become very, very pertinent,” he said.
Putting the Treatment Pieces Together in Type 2 Diabetes
The Evaluation of Ertugliflozin Efficacy and Safety Cardiovascular Outcomes Trial (VERTIS-CV) session will include the major cardiovascular, metabolic, renal, and safety outcomes for that drug, along with a meta-analysis of outcomes from trials of several different SGLT2 inhibitors.
All eyes will be on the VERTIS-CV presentation because ertugliflozin broke ranks with the other drugs in this class and failed to produce statistically significant drops in the relevant endpoints, as detailed in top-line data issued by the company in April.
And the provocatively titled session, “DAPA-HF Update: Have We Lost SGLT2 inhibitors to Cardiologists?!” will include a review of the trial’s main findings presented at the European Society of Cardiology meeting in September 2019, and published a few weeks later in the New England Journal of Medicine, along with new data on patient-centered and metabolic outcomes, and diabetes prevention. An independent commentator will presumably address the session title’s question.
Eckel, who has been working to establish a new cardiometabolic medicine subspecialty, commented: “I think we have not lost it, but I think SGLT2 inhibitors are a perfect example of why we need physicians trained in this overlap of diabetes medicine and cardiology.”
And, he said, we may be coming to the end of the CVOTs trial phenomenon.
“I think unless there’s a whole new class of drugs developed, we may be done with CVOTs for dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors, and glucagon-like peptide 1 (GLP-1) receptor agonists. We’ve learned a lot, and I’m not sure we need more other than mechanistic studies ... I don’t think we really know yet how SGLT2 inhibitors or GLP-1 agonists work,” Eckel said.
Metformin, on the other hand, has not been subject to a CVOT because it has been available as a generic since long before the US Food and Drug Administration mandated the CVOTs for new drugs for type 2 diabetes in 2008.
Such a trial is unlikely to be conducted at this point, but the new DPPOS data might actually come close, Florez noted.
The DPPOS is the observational follow-up of the landmark randomized DPP trial, which found that intensive lifestyle intervention and metformin reduced progression from prediabetes to type 2 diabetes.
Numerous additional outcomes have been reported over the years, but this will be the first-ever reporting of DPPOS data on both hard cardiovascular events and cancer incidence in people who have been continuously taking metformin for more than 20 years.
“There’s a lot of interest in whether metformin has an effect on cardiovascular events and cancer ... I think that’s going to be a very interesting session,” Florez said, noting that “short of a randomized clinical trial, which it’s hard to imagine would come to be, this is really, really good.”
Also examining metformin will be a debate on Sunday, “Should Metformin Be Considered First-Line Therapy for Individuals with Type 2 Diabetes With Established Arteriosclerotic Cardiovascular Disease (ASCVD) or at High Risk for ASCVD?”
And on Saturday, a debate will address another old-guard diabetes drug class, asking: “Is There a Current Place for Sulfonylureas in the Treatment of Type 2 Diabetes?”
Overall, Florez said, meeting attendees will come away with “a more clear understanding of the placement of SGLT2 inhibitors and GLP-1 agonists in the type 2 diabetes treatment algorithm.”
“What are the settings in which these [newer] drugs ought to be used, compared to the old-timers like metformin and sulfonylureas? One thing is having the trials, but the other is figuring out how you interpret these in deciding what happens at the point of care.”
Two more future-looking type 2 diabetes symposia of potential interest to clinicians are “Unraveling the Heterogeneity in Type 2 Diabetes” on Sunday and “Perspectives on the Future of Precision Diabetes Medicine — A Joint ADA/EASD Symposium” on Monday.
Type 1 Diabetes, Technology, and Kids
A symposium on Friday will feature four new clinical trials of automated insulin delivery systems for people with type 1 diabetes, the “US Advanced Hybrid Closed-Loop (AHCL) Pivotal Safety Study, FLAIR — An NIDDK-Sponsored International, Multi-site Randomized Crossover Trial of AHCL vs 670G,” the New Zealand AHCL randomized crossover trial, and the Horizon Automated Glucose Control System pre-pivotal trial data.
“Closed-loop devices are getting a lot of traction ... These trials will continue to advance the notion that these devices will narrow the glycemic range, prevent hypoglycemia, and improve quality of life because people don’t have to pay as much attention mentally to the management of the diabetes,” Florez said.
He added that although these trials “have been in the works for a while and they’re not big surprises, they continue to build a body of evidence suggesting that these devices will be part of our armamentarium in the very near future.”
And on Saturday, a debate will address the somewhat controversial question of whether continuous glucose monitoring in type 2 diabetes is worth the cost.
There will also be plenty of pediatric diabetes material presented this year, too.
On Sunday, there will be new insights from the Restoring Insulin Secretion (RISE) study, which examines prediabetes and type 2 diabetes in youth, and on Monday, 20-year data from the SEARCH for Diabetes in Youth Study will be reported.
And on Monday, the most recent findings from The Environmental Determinants of Diabetes in the Young (TEDDY) study of environmental triggers of type 1 diabetes will be presented.
All-Virtual Meeting: Pros and Cons
The all-virtual meeting format will have pluses and minuses, Eckel predicts.
Advantages include the fact that attendees don’t have to physically run from room to room or make difficult decisions about conflicting sessions.
“The fact that this meeting will be taking place in reality in terms of the timing of sessions, one can transition from one room to another in a matter of seconds if you want to,” he noted.
However, he observed, “a lot of interesting things happen in the hallways at meetings. Colleagues from around the world get together and knock heads about their ongoing research and potential collaborations can be formulated.
“Opportunities to engage with one another beyond the formality of the meeting is going to be lost to some extent.”
What’s more, the sessions will all be in Central US (Chicago) time, “So if you live in Thailand, the session may be occurring at a time when you’re in bed. If you want to see it live, then you’ve got to get up. Then you can ask a question.”
On the other hand, since all the content will be available online for 90 days, “if you want to stay in bed and you live in Thailand, you can get up a week from now during the day and log into a session you may have missed.”
Indeed, Florez said, “One silver lining of this virtual conference is that we’ve lowered the barriers for people to attend. It’s much more global. We’ve had an amazing influx of new registrants who were not planning on coming and were not registered for the original meeting and have registered since [more than 10,000 at the time of writing], and they continue to pile in.”
“We plan to reach people we haven’t reached before. The big question for ADA moving forward will be how much this can become a permanent feature, where even if we do it in person in the future, maybe we offer at least some virtual options so that our reach can go farther.”
Eckel has reported sitting on the scientific advisory board for a Kowa Company trial of pemafibrate and on an advisory board for Novo Nordisk. Florez has reported being a speaker for Novo Nordisk and receiving an honorarium from ADA for chairing the conference planning committee.
This article originally appeared on Medscape.com.
Do cinnamon supplements improve glycemic control in adults with T2DM?
EVIDENCE SUMMARY
A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.1 Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.
Studies of glycemic control produce mixed results
A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.2 Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.
Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.
A 2012 systematic review and meta-analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.3 Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.
RECOMMENDATIONS
The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.4
Editor’s Takeaway
Meta-analyses of multiple small, lower-quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.
1. Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013;11:452-459.
2. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database Syst Rev. 2012;(9):CD007170.
3. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: systematic review and meta-analysis. Clin Nutr. 2012;31:609-615.
4. American Diabetes Association. Standards of medical care in diabetes—2017. 4. Lifestyle management. Diabetes Care. 2017;40(suppl 1):S33-S43.
EVIDENCE SUMMARY
A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.1 Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.
Studies of glycemic control produce mixed results
A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.2 Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.
Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.
A 2012 systematic review and meta-analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.3 Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.
RECOMMENDATIONS
The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.4
Editor’s Takeaway
Meta-analyses of multiple small, lower-quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.
EVIDENCE SUMMARY
A 2013 systematic review of 10 randomized controlled trials (RCTs) with a total of 543 patients with type 2 diabetes evaluated the effect of cinnamon (120 mg/d to 6 g/d) on measures of glycemic control.1 Study duration ranged from 4 to 18 weeks. Fasting glucose levels demonstrated small but statistically significant reductions (−24.6 mg/dL; 95% confidence interval [CI], −40.5 to −8.7 mg/dL), whereas hemoglobin A1C levels didn’t differ between treatment and control groups (−0.16%; 95% CI, −0.39% to 0.02%). Study limitations included heterogeneity of cinnamon dosing and formulation and concurrent use of oral hypoglycemic agents.
Studies of glycemic control produce mixed results
A 2012 systematic review of 10 RCTs comprising 577 patients with type 1 (72 patients) or type 2 (505 patients) diabetes evaluated the effects of cinnamon supplements (mean dose, 1.9 g/d) on glycemic control compared with placebo, active control, or no treatment.2 Study duration ranged from 4.3 to 16 weeks (mean, 10.8 weeks). Studies evaluating hemoglobin A1C lasted at least 12 weeks.
Fasting glucose as measured in 8 studies (338 patients) and hemoglobin A1C as measured in 6 studies (405 patients) didn’t differ between treatment groups (mean fasting glucose difference = −0.91 mmol/L; 95% CI, −1.93 to 0.11; mean hemoglobin A1C difference = −0.06; 95% CI, −0.29 to 0.18). The risk for bias was assessed as high or unclear in 8 studies and moderate in 2 studies.
A 2012 systematic review and meta-analysis of 6 RCTs including 435 patients with type 2 diabetes evaluated the impact of cinnamon supplements (1 to 6 g/d) on glycemic control.3 Participants consumed cinnamon for 40 to 160 days. Hemoglobin A1C decreased by 0.09% (95% CI, 0.04% to 0.14%) in 5 trials (375 patients), and fasting glucose decreased by 0.84 mmol/L (CI, 0.66 to 1.02) in 5 trials (326 patients). Study limitations included heterogeneity of cinnamon dosing and study population.
RECOMMENDATIONS
The American Diabetes Association finds insufficient evidence to support the use of herbs or spices, including cinnamon, in treating diabetes.4
Editor’s Takeaway
Meta-analyses of multiple small, lower-quality studies yield uncertain conclusions. If cinnamon does improve glycemic control, the benefit is minimal—but so is therisk.
1. Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013;11:452-459.
2. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database Syst Rev. 2012;(9):CD007170.
3. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: systematic review and meta-analysis. Clin Nutr. 2012;31:609-615.
4. American Diabetes Association. Standards of medical care in diabetes—2017. 4. Lifestyle management. Diabetes Care. 2017;40(suppl 1):S33-S43.
1. Allen RW, Schwartzman E, Baker WL, et al. Cinnamon use in type 2 diabetes: an updated systematic review and meta-analysis. Ann Fam Med. 2013;11:452-459.
2. Leach MJ, Kumar S. Cinnamon for diabetes mellitus. Cochrane Database Syst Rev. 2012;(9):CD007170.
3. Akilen R, Tsiami A, Devendra D, et al. Cinnamon in glycaemic control: systematic review and meta-analysis. Clin Nutr. 2012;31:609-615.
4. American Diabetes Association. Standards of medical care in diabetes—2017. 4. Lifestyle management. Diabetes Care. 2017;40(suppl 1):S33-S43.
EVIDENCE-BASED ANSWER:
The answer isn’t clear. Cinnamon supplements for adults with type 2 diabetes haven’t been shown to decrease hemoglobin A1C (strength of recommendation [SOR]: C, multiple systematic reviews of disease-oriented outcomes).
Cinnamon supplements have shown inconsistent effects on fasting glucose levels (SOR: C, multiple systematic reviews and a single meta-analysis of disease-oriented outcomes). Supplements decreased fasting glucose levels in some studies, but the evidence isn’t consistent and hasn’t been correlated with clinically significant improvements in glycemic control.
Hemiballismus in Patients With Poorly Controlled Type 2 Diabetes Mellitus
Hemiballismus is an acquired hyperkinetic movement disorder characterized by unilateral, involuntary, often large-amplitude limb movements. Ballistic movements are now considered to be on the choreiform spectrum.1 Movements usually involve both the arm and leg, and in half of cases, facial movements such as tongue clucking and grimacing are seen.2,3 Presentations of hemiballismus vary in severity from intermittent to nearly continuous movements, which, in some cases, may lead to exhaustion, injury, or disability. Some patients are unable to ambulate or feed themselves with the affected limb.
Background
The 2 most common causes of hemichorea-hemiballismus are stroke and hyperglycemia, with an incidence of 4% and unknown incidence, respectively.1,3,4 Other causes include HIV, traumatic brain injury, encephalitis, vasculitis, mass effect, multiple sclerosis, and adverse drug reactions. 4-7 Acute or subacute hemiballismus is classically attributed to a lesion in subthalamic nucleus (STN), but this is true only in a minority of cases. Hemiballismus can be caused by any abnormality in various subnuclei of the basal ganglia, including the classic location in the STN, striatum, and globus pallidus.4 Evidence shows the lesions typically involve a functional network connected to the posterolateral putamen.8
Although not commonly recognized, hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is the second most common cause of hemichoreahemiballismus. 3 Over the past 90 years, numerous case reports have described patients with DM with acute and subacute onset of hemiballistic and hemichoreiform movements while in a hyperglycemic state or after its resolution. Reported cases have been limited to small numbers of patients with only a few larger-scale reviews of more than 20 patients.7,9 Most reported cases involve geriatric patients and more commonly, females of Eastern Asian descent with an average age of onset of 71 years.4,10 Patients typically present with glucose levels from 500 to 1,000 mg/dL and hemoglobin A1c (HbA1c) levels almost double the normal values. Interestingly, neuroimaging findings in these patients have consistently shown hyperintense signal in the contralateral basal ganglia on T1-weighted magnetic resonance images (MRIs). Noncontrast computed tomography (CT) shows well-defined unilateral increased density in the contralateral basal ganglia without mass effect.1,9,11
This report aims to illustrate and enhance the understanding of hemiballismus associated with hyperglycemia. One patient presented to the US Department of Veterans Affairs (VA) Bay Pines VA Healthcare System (BPVAHCS) in Florida, which motivated us to search for other similar cases. We reviewed the charts of 2 other patients who presented to BPVAHCS over the past 10 years. The first case presented with severe hyperglycemia and abnormal movements that were not clearly diagnosed as hemiballismus. MRI findings were characteristic and assisted in making the diagnosis. The second case was misdiagnosed as hemiballismus secondary to ischemic stroke. The third case was initially diagnosed as conversion disorder until movements worsened and the correct diagnosis of hyperglycemia-induced hemichorea hemiballismus was confirmed by the pathognomonic neuroimaging findings.
Case Presentations
Case 1
A 65-year-old male with a history of uncontrolled T2DM presented with repetitive twitching and kicking movements that involved his left upper and lower extremities for 3 weeks. The patient reported that he did not take his medications or follow the recommended diabetes diet. His HbA1c on admission was 12.2% with a serum glucose of 254 mg/dL. The MRI showed a hyperintense T1 signal within the right basal ganglia including the right caudate with sparing of the internal capsule (Figure 1). There was no associated mass effect or restricted diffusion. It was compatible with a diagnosis of hyperglycemia- induced hemichorea-hemiballismus. The patient was advised to resume taking glipizide 10 mg daily, metformin 1,000 mg by mouth twice daily, and to begin 10 units of 70/30 insulin aspart 15 minutes before meals twice daily, and to follow a low carbohydrate diet, with reduce dietary intake of sugar. At his 1-month follow-up visit, the patient reported an improvement in his involuntary movements. At the 5-month follow-up, the patient’s HbA1c level was 10.4% and his hyperkinetic movements had completely resolved.
Case 2
of T2DM, hypertension, and hyperlipidemia was admitted due to increased jerky movements in the left upper extremity. On admission, his vital signs were within normal limits and his physical examination demonstrated choreoathetoid movements with ballistic components of his left upper extremity. His laboratory results showed a glucose level of 528 mg/dL with a HbA1c of 16.3%. An initial CT obtained in the emergency department (ED) demonstrated a well-defined hyperdensity in the striatal (caudate and lentiform nucleus) region (Figure 2). There was no associated edema/mass effect that would be typical for an intracranial hemorrhage.
An MRI obtained 1 week later showed hyperintense TI signal corresponding to the basal ganglia (Figure 3). In addition, there was a questionable lacunar infarct in the right internal capsule. Due to lack of awareness regarding hyperglycemic associated basal ganglia changes, the patient’s movement disorder was presumed to be ischemic in etiology. The patient was prescribed oral amantadine 100 mg 3 times daily for the hemiballismus in conjunction with treatment of his T2DM. The only follow-up occurred 5 weeks later, which showed no improvement of uncontrollable movements. Imaging at that time (not available) indicated the persistence of the abnormal signal in the right basal ganglia. This patient died later that year without further follow-up.
Case 3
A 78-year-old white male with a history of syncope, transient ischemic attacks (TIAs), and poorly controlled T2DM presented with a 1-month history of progressively worsening involuntary, left-sided movements that began in his left shoulder and advanced to involve his arm, hand, and leg, and the left side of his face with grimacing and clucking of his tongue. Three weeks earlier, the patient had been discharged from the ED with a diagnosis of conversion disorder particularly because he experienced decreased movements when given a dose of Vitamin D. It was overlooked that administration of haloperidol had occurred a few hours before, and because the sounds made by his tongue were not felt to be consistent with a known movement disorder. A MRI of the brain was read as normal.
The patient returned 3 weeks later (the original presentation) due to his inability to perform activities of daily living because of his worsening involuntary movements. On admission, his HbA1c was 11.1% and his glucose was 167 mg/dL. On chart review, it was revealed that the patient’s HbA1c had been > 9% for the past 3 years with an increase from 10.1% to 11.1% in the 3 months preceding the onset of his symptoms.
On admission a MRI showed a unilateral right-sided T1 hyperintensity in the basal ganglia, no acute ischemia (Figure 4). In retrospect, subtle increased T1 signal can be seen on the earlier MRI (Figure 5). In view of the patient’s left-sided symptoms, DM, and MRI findings, a diagnosis of hyperglycemia-induced hemichorea- hemiballismus was made as the etiology of the patient’s symptoms.
The patient was prescribed numerous medications to control his hyperkinesia including (and in combination): benztropine, gabapentin, baclofen, diphenhydramine, benzodiazepines, risperidone, olanzapine, and valproic acid, which did not control his movements. Ultimately, his hyperglycemic hemiballismus improved with tight glycemic control and oral tetrabenazine 12.5 mg twice daily. This patient underwent a protracted course of treatment with 17 days of inpatient medical admission, 3 weeks inpatient rehabilitation, and subsequent transfer to an assisted living facility.
Discussion
The 3 cases presented in this report contribute to the evidence that severe persistent hyperglycemia can result in movement disorders that mimic those seen after basal ganglia strokes. As with Case 2, past literature describes many cases of acute hyperglycemic episodes with glucose ranging from 500 to 1,000 mg/mL presenting with hemiballismus.1,3 However, there are many cases that describe hemiballismus occurring after glycemic correction, persisting despite glycemic correction, and presenting without an acute hyperglycemic episode, but in the setting of elevated HbA1c, as in Case 3.12,13 Notably, all 3 cases in this series had marked elevation in their HbA1c levels, which suggests that a more chronic hyperglycemic state or multiple shorter periods of hyperglycemia may be necessary to produce the described hyperkinetic movements.
Case reports describe the pathognomonic T1 hyperintensity of the basal ganglia that is identified in all 3 cases presented here. While the exact etiology remains unclear, the to metabolic derangements caused by hyperviscosity of the blood in the small end arteries feeding the basal ganglia.3,11 These abnormalities in turn interrupt the signaling cascade with abnormal firing rates or firing patterns, leading to reduced inhibition of the motor thalamus and ultimately present as hemiballismus.1,3,7 While most cases presented with unilateral hyperkinesis and associated contralateral basal ganglia abnormalities, there are reports of both unilateral and bilateral movements associated with bilateral basal ganglia hyperintensities on imaging. 9 The predilection for unilateral brain lesions may be explained by the varying degree of small vessel disease in different areas of the brain leading to perfusion deficits worsened by hyper viscosity. Further research into this is required to elucidate the exact pathophysiologic mechanism.
The course of disease for patients ranges from resolution within hours of tight glycemic control to persistent movements for > 3 months with a gradual improvement in severity.12,13 Treatments center on the importance of tight glycemic control to protect against the protracted course described in Case 3. Swift recognition of this rare condition is critical because improved glycemic control decreases the severity and duration of this disease. The significant disability associated with Case 3 highlights the need for prompt recognition and early, aggressive glycemic management to prevent the progression of hemiballismus. In addition to glycemic control, various CNS medications such as typical and atypical antipsychotics and tetrabenazine are firstline therapy with chemodenervation and surgical lesioning in cases unresponsive to medication therapy.
When unrecognized, hyperglycemic hemiballismus is associated with significant morbidity and mortality. The patients presented in this report were subject to either delayed diagnosis or misdiagnosis as stroke or psychiatric disorder. The rarity of the disorder, lack of evidence delineating pathogenesis and causality, low level of awareness, and varying presentations of patients all contribute to the challenge of recognizing, diagnosing, and treating hemiballismus due to hyperglycemia. This challenge can subsequently result in deteriorating symptoms, prolonged hospital stays, and unnecessary health care costs.
Conclusion
While hemiballismus due to severe persistent hyperglycemia is rare, the goal of this report is to highlight its occurrence in patients with T2DM. Further research can help develop a standardized, effective treatment strategy for these patients. Currently, lowering and maintaining appropriate glucose and HbA1c levels is the most effective treatment approach. Potential areas of research include alternative medical and surgical treatment interventions for patients while glycemic control is being achieved or for those who fail to benefit from glycemic control alone. Some success has been demonstrated with the use of antidopaminergic medications such as atypical antipsychotics and tetrabenazine and these medications should be considered when tight, sustained glycemic control alone is not successful in treating this disorder in the acute stages. Hopefully, with increasing awareness and recognition of hemiballismus related to hyperglycemia, more large-scale clinical trials can be conducted that will result in an effective treatment strategy for this devastating disorder.
1. Hawley JS, Weiner WJ. Hemiballismus: current concepts and review. Parkinsonism Relat Disord. 2012;18(2):125‐129. doi:10.1016/j.parkreldis.2011.08.015
2. Gasca-Salas C, Lang AE. Paroxysmal Hemiballism/ Hemichorea Resulting from Transient Ischemic Attacks. Mov Disord Clin Pract. 2015;3(3):303‐305. doi:10.1002/mdc3.12268
3. Garcia-Grimshaw MA, Jimenez-Ruiz A, Ornelas-Velazquez A, Luna-Armenta A, Gutierrez-Manjarrez FA. New-onset diabetes presenting as monoballism secondary to a mixed hyperglycemic crisis. Cureus. 2018;10(6):e2882. doi:10.7759/cureus.2882
4. Postuma RB, Lang AE. Hemiballism: revisiting a classic disorder. Lancet Neurol. 2003;2(11):661‐668. doi:10.1016/s1474-4422(03)00554-4
5. Gallo BV, Shulman LM, Weiner WJ, Petito CK, Berger JR. HIV encephalitis presenting with severe generalized chorea. Neurology. 1996;46(4):1163‐1165. doi:10.1212/wnl.46.4.1163
6. Provenzale JM, Glass JP. Hemiballismus: CT and MR findings. J Comput Assist Tomogr. 1995;19(4):537‐540.
7. Hodde M, Rowe KE, Surapaneni K, Terrigno P, Brighenti A, Altschuler EL. Management of severe hemiballismus: treatment challenges in the acute inpatient rehabilitation setting: a case presentation. PMR. 2017;9(7):732‐735. doi:10.1016/j.pmrj.2016.10.023
8. Laganiere S, Boes AD, Fox MD. Network localization of hemichorea-hemiballismus. Neurology. 2016;86(23):2187‐2195. doi:10.1212/WNL.0000000000002741
9. Cosentino C, Torres L, Nuñez Y, Suarez R, Velez M, Flores M. Hemichorea/hemiballism associated with hyperglycemia: report of 20 cases. Tremor Other Hyperkinet Mov (NY). 2016;6:402. doi:10.7916/D8DN454P
10. Oh SH, Lee KY, Im JH, Lee MS. Chorea associated with non-ketotic hyperglycemia and hyperintensity basal ganglia lesion on T1-weighted brain MRI study: a metaanalysis of 53 cases including four present cases. J Neurol Sci. 2002;200(1-2):57‐62. doi:10.1016/s0022-510x(02)00133-8
11. Carrion DM, Carrion AF. Non-ketotic hyperglycaemia hemichorea-hemiballismus and acute ischaemic stroke. BMJ Case Rep. 2013;2013:bcr2012008359. doi:10.1136/bcr-2012-008359
12. Cho HS, Hong CT, Chan L. Hemichorea after hyperglycemia correction: a case report and a short review of hyperglycemia-related hemichorea at the euglycemic state. Medicine (Baltimore). 2018;97(10):e0076. doi:10.1097/MD.0000000000010076
13. Lin YC, Lin YC. Prolonged hemiballism after the remission of non-ketotic hyperosmolar syndrome. BMJ Case Rep. 2012;2012:bcr0120125627. doi:10.1136/bcr.01.2012.5627
Hemiballismus is an acquired hyperkinetic movement disorder characterized by unilateral, involuntary, often large-amplitude limb movements. Ballistic movements are now considered to be on the choreiform spectrum.1 Movements usually involve both the arm and leg, and in half of cases, facial movements such as tongue clucking and grimacing are seen.2,3 Presentations of hemiballismus vary in severity from intermittent to nearly continuous movements, which, in some cases, may lead to exhaustion, injury, or disability. Some patients are unable to ambulate or feed themselves with the affected limb.
Background
The 2 most common causes of hemichorea-hemiballismus are stroke and hyperglycemia, with an incidence of 4% and unknown incidence, respectively.1,3,4 Other causes include HIV, traumatic brain injury, encephalitis, vasculitis, mass effect, multiple sclerosis, and adverse drug reactions. 4-7 Acute or subacute hemiballismus is classically attributed to a lesion in subthalamic nucleus (STN), but this is true only in a minority of cases. Hemiballismus can be caused by any abnormality in various subnuclei of the basal ganglia, including the classic location in the STN, striatum, and globus pallidus.4 Evidence shows the lesions typically involve a functional network connected to the posterolateral putamen.8
Although not commonly recognized, hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is the second most common cause of hemichoreahemiballismus. 3 Over the past 90 years, numerous case reports have described patients with DM with acute and subacute onset of hemiballistic and hemichoreiform movements while in a hyperglycemic state or after its resolution. Reported cases have been limited to small numbers of patients with only a few larger-scale reviews of more than 20 patients.7,9 Most reported cases involve geriatric patients and more commonly, females of Eastern Asian descent with an average age of onset of 71 years.4,10 Patients typically present with glucose levels from 500 to 1,000 mg/dL and hemoglobin A1c (HbA1c) levels almost double the normal values. Interestingly, neuroimaging findings in these patients have consistently shown hyperintense signal in the contralateral basal ganglia on T1-weighted magnetic resonance images (MRIs). Noncontrast computed tomography (CT) shows well-defined unilateral increased density in the contralateral basal ganglia without mass effect.1,9,11
This report aims to illustrate and enhance the understanding of hemiballismus associated with hyperglycemia. One patient presented to the US Department of Veterans Affairs (VA) Bay Pines VA Healthcare System (BPVAHCS) in Florida, which motivated us to search for other similar cases. We reviewed the charts of 2 other patients who presented to BPVAHCS over the past 10 years. The first case presented with severe hyperglycemia and abnormal movements that were not clearly diagnosed as hemiballismus. MRI findings were characteristic and assisted in making the diagnosis. The second case was misdiagnosed as hemiballismus secondary to ischemic stroke. The third case was initially diagnosed as conversion disorder until movements worsened and the correct diagnosis of hyperglycemia-induced hemichorea hemiballismus was confirmed by the pathognomonic neuroimaging findings.
Case Presentations
Case 1
A 65-year-old male with a history of uncontrolled T2DM presented with repetitive twitching and kicking movements that involved his left upper and lower extremities for 3 weeks. The patient reported that he did not take his medications or follow the recommended diabetes diet. His HbA1c on admission was 12.2% with a serum glucose of 254 mg/dL. The MRI showed a hyperintense T1 signal within the right basal ganglia including the right caudate with sparing of the internal capsule (Figure 1). There was no associated mass effect or restricted diffusion. It was compatible with a diagnosis of hyperglycemia- induced hemichorea-hemiballismus. The patient was advised to resume taking glipizide 10 mg daily, metformin 1,000 mg by mouth twice daily, and to begin 10 units of 70/30 insulin aspart 15 minutes before meals twice daily, and to follow a low carbohydrate diet, with reduce dietary intake of sugar. At his 1-month follow-up visit, the patient reported an improvement in his involuntary movements. At the 5-month follow-up, the patient’s HbA1c level was 10.4% and his hyperkinetic movements had completely resolved.
Case 2
of T2DM, hypertension, and hyperlipidemia was admitted due to increased jerky movements in the left upper extremity. On admission, his vital signs were within normal limits and his physical examination demonstrated choreoathetoid movements with ballistic components of his left upper extremity. His laboratory results showed a glucose level of 528 mg/dL with a HbA1c of 16.3%. An initial CT obtained in the emergency department (ED) demonstrated a well-defined hyperdensity in the striatal (caudate and lentiform nucleus) region (Figure 2). There was no associated edema/mass effect that would be typical for an intracranial hemorrhage.
An MRI obtained 1 week later showed hyperintense TI signal corresponding to the basal ganglia (Figure 3). In addition, there was a questionable lacunar infarct in the right internal capsule. Due to lack of awareness regarding hyperglycemic associated basal ganglia changes, the patient’s movement disorder was presumed to be ischemic in etiology. The patient was prescribed oral amantadine 100 mg 3 times daily for the hemiballismus in conjunction with treatment of his T2DM. The only follow-up occurred 5 weeks later, which showed no improvement of uncontrollable movements. Imaging at that time (not available) indicated the persistence of the abnormal signal in the right basal ganglia. This patient died later that year without further follow-up.
Case 3
A 78-year-old white male with a history of syncope, transient ischemic attacks (TIAs), and poorly controlled T2DM presented with a 1-month history of progressively worsening involuntary, left-sided movements that began in his left shoulder and advanced to involve his arm, hand, and leg, and the left side of his face with grimacing and clucking of his tongue. Three weeks earlier, the patient had been discharged from the ED with a diagnosis of conversion disorder particularly because he experienced decreased movements when given a dose of Vitamin D. It was overlooked that administration of haloperidol had occurred a few hours before, and because the sounds made by his tongue were not felt to be consistent with a known movement disorder. A MRI of the brain was read as normal.
The patient returned 3 weeks later (the original presentation) due to his inability to perform activities of daily living because of his worsening involuntary movements. On admission, his HbA1c was 11.1% and his glucose was 167 mg/dL. On chart review, it was revealed that the patient’s HbA1c had been > 9% for the past 3 years with an increase from 10.1% to 11.1% in the 3 months preceding the onset of his symptoms.
On admission a MRI showed a unilateral right-sided T1 hyperintensity in the basal ganglia, no acute ischemia (Figure 4). In retrospect, subtle increased T1 signal can be seen on the earlier MRI (Figure 5). In view of the patient’s left-sided symptoms, DM, and MRI findings, a diagnosis of hyperglycemia-induced hemichorea- hemiballismus was made as the etiology of the patient’s symptoms.
The patient was prescribed numerous medications to control his hyperkinesia including (and in combination): benztropine, gabapentin, baclofen, diphenhydramine, benzodiazepines, risperidone, olanzapine, and valproic acid, which did not control his movements. Ultimately, his hyperglycemic hemiballismus improved with tight glycemic control and oral tetrabenazine 12.5 mg twice daily. This patient underwent a protracted course of treatment with 17 days of inpatient medical admission, 3 weeks inpatient rehabilitation, and subsequent transfer to an assisted living facility.
Discussion
The 3 cases presented in this report contribute to the evidence that severe persistent hyperglycemia can result in movement disorders that mimic those seen after basal ganglia strokes. As with Case 2, past literature describes many cases of acute hyperglycemic episodes with glucose ranging from 500 to 1,000 mg/mL presenting with hemiballismus.1,3 However, there are many cases that describe hemiballismus occurring after glycemic correction, persisting despite glycemic correction, and presenting without an acute hyperglycemic episode, but in the setting of elevated HbA1c, as in Case 3.12,13 Notably, all 3 cases in this series had marked elevation in their HbA1c levels, which suggests that a more chronic hyperglycemic state or multiple shorter periods of hyperglycemia may be necessary to produce the described hyperkinetic movements.
Case reports describe the pathognomonic T1 hyperintensity of the basal ganglia that is identified in all 3 cases presented here. While the exact etiology remains unclear, the to metabolic derangements caused by hyperviscosity of the blood in the small end arteries feeding the basal ganglia.3,11 These abnormalities in turn interrupt the signaling cascade with abnormal firing rates or firing patterns, leading to reduced inhibition of the motor thalamus and ultimately present as hemiballismus.1,3,7 While most cases presented with unilateral hyperkinesis and associated contralateral basal ganglia abnormalities, there are reports of both unilateral and bilateral movements associated with bilateral basal ganglia hyperintensities on imaging. 9 The predilection for unilateral brain lesions may be explained by the varying degree of small vessel disease in different areas of the brain leading to perfusion deficits worsened by hyper viscosity. Further research into this is required to elucidate the exact pathophysiologic mechanism.
The course of disease for patients ranges from resolution within hours of tight glycemic control to persistent movements for > 3 months with a gradual improvement in severity.12,13 Treatments center on the importance of tight glycemic control to protect against the protracted course described in Case 3. Swift recognition of this rare condition is critical because improved glycemic control decreases the severity and duration of this disease. The significant disability associated with Case 3 highlights the need for prompt recognition and early, aggressive glycemic management to prevent the progression of hemiballismus. In addition to glycemic control, various CNS medications such as typical and atypical antipsychotics and tetrabenazine are firstline therapy with chemodenervation and surgical lesioning in cases unresponsive to medication therapy.
When unrecognized, hyperglycemic hemiballismus is associated with significant morbidity and mortality. The patients presented in this report were subject to either delayed diagnosis or misdiagnosis as stroke or psychiatric disorder. The rarity of the disorder, lack of evidence delineating pathogenesis and causality, low level of awareness, and varying presentations of patients all contribute to the challenge of recognizing, diagnosing, and treating hemiballismus due to hyperglycemia. This challenge can subsequently result in deteriorating symptoms, prolonged hospital stays, and unnecessary health care costs.
Conclusion
While hemiballismus due to severe persistent hyperglycemia is rare, the goal of this report is to highlight its occurrence in patients with T2DM. Further research can help develop a standardized, effective treatment strategy for these patients. Currently, lowering and maintaining appropriate glucose and HbA1c levels is the most effective treatment approach. Potential areas of research include alternative medical and surgical treatment interventions for patients while glycemic control is being achieved or for those who fail to benefit from glycemic control alone. Some success has been demonstrated with the use of antidopaminergic medications such as atypical antipsychotics and tetrabenazine and these medications should be considered when tight, sustained glycemic control alone is not successful in treating this disorder in the acute stages. Hopefully, with increasing awareness and recognition of hemiballismus related to hyperglycemia, more large-scale clinical trials can be conducted that will result in an effective treatment strategy for this devastating disorder.
Hemiballismus is an acquired hyperkinetic movement disorder characterized by unilateral, involuntary, often large-amplitude limb movements. Ballistic movements are now considered to be on the choreiform spectrum.1 Movements usually involve both the arm and leg, and in half of cases, facial movements such as tongue clucking and grimacing are seen.2,3 Presentations of hemiballismus vary in severity from intermittent to nearly continuous movements, which, in some cases, may lead to exhaustion, injury, or disability. Some patients are unable to ambulate or feed themselves with the affected limb.
Background
The 2 most common causes of hemichorea-hemiballismus are stroke and hyperglycemia, with an incidence of 4% and unknown incidence, respectively.1,3,4 Other causes include HIV, traumatic brain injury, encephalitis, vasculitis, mass effect, multiple sclerosis, and adverse drug reactions. 4-7 Acute or subacute hemiballismus is classically attributed to a lesion in subthalamic nucleus (STN), but this is true only in a minority of cases. Hemiballismus can be caused by any abnormality in various subnuclei of the basal ganglia, including the classic location in the STN, striatum, and globus pallidus.4 Evidence shows the lesions typically involve a functional network connected to the posterolateral putamen.8
Although not commonly recognized, hyperglycemia in patients with type 2 diabetes mellitus (T2DM) is the second most common cause of hemichoreahemiballismus. 3 Over the past 90 years, numerous case reports have described patients with DM with acute and subacute onset of hemiballistic and hemichoreiform movements while in a hyperglycemic state or after its resolution. Reported cases have been limited to small numbers of patients with only a few larger-scale reviews of more than 20 patients.7,9 Most reported cases involve geriatric patients and more commonly, females of Eastern Asian descent with an average age of onset of 71 years.4,10 Patients typically present with glucose levels from 500 to 1,000 mg/dL and hemoglobin A1c (HbA1c) levels almost double the normal values. Interestingly, neuroimaging findings in these patients have consistently shown hyperintense signal in the contralateral basal ganglia on T1-weighted magnetic resonance images (MRIs). Noncontrast computed tomography (CT) shows well-defined unilateral increased density in the contralateral basal ganglia without mass effect.1,9,11
This report aims to illustrate and enhance the understanding of hemiballismus associated with hyperglycemia. One patient presented to the US Department of Veterans Affairs (VA) Bay Pines VA Healthcare System (BPVAHCS) in Florida, which motivated us to search for other similar cases. We reviewed the charts of 2 other patients who presented to BPVAHCS over the past 10 years. The first case presented with severe hyperglycemia and abnormal movements that were not clearly diagnosed as hemiballismus. MRI findings were characteristic and assisted in making the diagnosis. The second case was misdiagnosed as hemiballismus secondary to ischemic stroke. The third case was initially diagnosed as conversion disorder until movements worsened and the correct diagnosis of hyperglycemia-induced hemichorea hemiballismus was confirmed by the pathognomonic neuroimaging findings.
Case Presentations
Case 1
A 65-year-old male with a history of uncontrolled T2DM presented with repetitive twitching and kicking movements that involved his left upper and lower extremities for 3 weeks. The patient reported that he did not take his medications or follow the recommended diabetes diet. His HbA1c on admission was 12.2% with a serum glucose of 254 mg/dL. The MRI showed a hyperintense T1 signal within the right basal ganglia including the right caudate with sparing of the internal capsule (Figure 1). There was no associated mass effect or restricted diffusion. It was compatible with a diagnosis of hyperglycemia- induced hemichorea-hemiballismus. The patient was advised to resume taking glipizide 10 mg daily, metformin 1,000 mg by mouth twice daily, and to begin 10 units of 70/30 insulin aspart 15 minutes before meals twice daily, and to follow a low carbohydrate diet, with reduce dietary intake of sugar. At his 1-month follow-up visit, the patient reported an improvement in his involuntary movements. At the 5-month follow-up, the patient’s HbA1c level was 10.4% and his hyperkinetic movements had completely resolved.
Case 2
of T2DM, hypertension, and hyperlipidemia was admitted due to increased jerky movements in the left upper extremity. On admission, his vital signs were within normal limits and his physical examination demonstrated choreoathetoid movements with ballistic components of his left upper extremity. His laboratory results showed a glucose level of 528 mg/dL with a HbA1c of 16.3%. An initial CT obtained in the emergency department (ED) demonstrated a well-defined hyperdensity in the striatal (caudate and lentiform nucleus) region (Figure 2). There was no associated edema/mass effect that would be typical for an intracranial hemorrhage.
An MRI obtained 1 week later showed hyperintense TI signal corresponding to the basal ganglia (Figure 3). In addition, there was a questionable lacunar infarct in the right internal capsule. Due to lack of awareness regarding hyperglycemic associated basal ganglia changes, the patient’s movement disorder was presumed to be ischemic in etiology. The patient was prescribed oral amantadine 100 mg 3 times daily for the hemiballismus in conjunction with treatment of his T2DM. The only follow-up occurred 5 weeks later, which showed no improvement of uncontrollable movements. Imaging at that time (not available) indicated the persistence of the abnormal signal in the right basal ganglia. This patient died later that year without further follow-up.
Case 3
A 78-year-old white male with a history of syncope, transient ischemic attacks (TIAs), and poorly controlled T2DM presented with a 1-month history of progressively worsening involuntary, left-sided movements that began in his left shoulder and advanced to involve his arm, hand, and leg, and the left side of his face with grimacing and clucking of his tongue. Three weeks earlier, the patient had been discharged from the ED with a diagnosis of conversion disorder particularly because he experienced decreased movements when given a dose of Vitamin D. It was overlooked that administration of haloperidol had occurred a few hours before, and because the sounds made by his tongue were not felt to be consistent with a known movement disorder. A MRI of the brain was read as normal.
The patient returned 3 weeks later (the original presentation) due to his inability to perform activities of daily living because of his worsening involuntary movements. On admission, his HbA1c was 11.1% and his glucose was 167 mg/dL. On chart review, it was revealed that the patient’s HbA1c had been > 9% for the past 3 years with an increase from 10.1% to 11.1% in the 3 months preceding the onset of his symptoms.
On admission a MRI showed a unilateral right-sided T1 hyperintensity in the basal ganglia, no acute ischemia (Figure 4). In retrospect, subtle increased T1 signal can be seen on the earlier MRI (Figure 5). In view of the patient’s left-sided symptoms, DM, and MRI findings, a diagnosis of hyperglycemia-induced hemichorea- hemiballismus was made as the etiology of the patient’s symptoms.
The patient was prescribed numerous medications to control his hyperkinesia including (and in combination): benztropine, gabapentin, baclofen, diphenhydramine, benzodiazepines, risperidone, olanzapine, and valproic acid, which did not control his movements. Ultimately, his hyperglycemic hemiballismus improved with tight glycemic control and oral tetrabenazine 12.5 mg twice daily. This patient underwent a protracted course of treatment with 17 days of inpatient medical admission, 3 weeks inpatient rehabilitation, and subsequent transfer to an assisted living facility.
Discussion
The 3 cases presented in this report contribute to the evidence that severe persistent hyperglycemia can result in movement disorders that mimic those seen after basal ganglia strokes. As with Case 2, past literature describes many cases of acute hyperglycemic episodes with glucose ranging from 500 to 1,000 mg/mL presenting with hemiballismus.1,3 However, there are many cases that describe hemiballismus occurring after glycemic correction, persisting despite glycemic correction, and presenting without an acute hyperglycemic episode, but in the setting of elevated HbA1c, as in Case 3.12,13 Notably, all 3 cases in this series had marked elevation in their HbA1c levels, which suggests that a more chronic hyperglycemic state or multiple shorter periods of hyperglycemia may be necessary to produce the described hyperkinetic movements.
Case reports describe the pathognomonic T1 hyperintensity of the basal ganglia that is identified in all 3 cases presented here. While the exact etiology remains unclear, the to metabolic derangements caused by hyperviscosity of the blood in the small end arteries feeding the basal ganglia.3,11 These abnormalities in turn interrupt the signaling cascade with abnormal firing rates or firing patterns, leading to reduced inhibition of the motor thalamus and ultimately present as hemiballismus.1,3,7 While most cases presented with unilateral hyperkinesis and associated contralateral basal ganglia abnormalities, there are reports of both unilateral and bilateral movements associated with bilateral basal ganglia hyperintensities on imaging. 9 The predilection for unilateral brain lesions may be explained by the varying degree of small vessel disease in different areas of the brain leading to perfusion deficits worsened by hyper viscosity. Further research into this is required to elucidate the exact pathophysiologic mechanism.
The course of disease for patients ranges from resolution within hours of tight glycemic control to persistent movements for > 3 months with a gradual improvement in severity.12,13 Treatments center on the importance of tight glycemic control to protect against the protracted course described in Case 3. Swift recognition of this rare condition is critical because improved glycemic control decreases the severity and duration of this disease. The significant disability associated with Case 3 highlights the need for prompt recognition and early, aggressive glycemic management to prevent the progression of hemiballismus. In addition to glycemic control, various CNS medications such as typical and atypical antipsychotics and tetrabenazine are firstline therapy with chemodenervation and surgical lesioning in cases unresponsive to medication therapy.
When unrecognized, hyperglycemic hemiballismus is associated with significant morbidity and mortality. The patients presented in this report were subject to either delayed diagnosis or misdiagnosis as stroke or psychiatric disorder. The rarity of the disorder, lack of evidence delineating pathogenesis and causality, low level of awareness, and varying presentations of patients all contribute to the challenge of recognizing, diagnosing, and treating hemiballismus due to hyperglycemia. This challenge can subsequently result in deteriorating symptoms, prolonged hospital stays, and unnecessary health care costs.
Conclusion
While hemiballismus due to severe persistent hyperglycemia is rare, the goal of this report is to highlight its occurrence in patients with T2DM. Further research can help develop a standardized, effective treatment strategy for these patients. Currently, lowering and maintaining appropriate glucose and HbA1c levels is the most effective treatment approach. Potential areas of research include alternative medical and surgical treatment interventions for patients while glycemic control is being achieved or for those who fail to benefit from glycemic control alone. Some success has been demonstrated with the use of antidopaminergic medications such as atypical antipsychotics and tetrabenazine and these medications should be considered when tight, sustained glycemic control alone is not successful in treating this disorder in the acute stages. Hopefully, with increasing awareness and recognition of hemiballismus related to hyperglycemia, more large-scale clinical trials can be conducted that will result in an effective treatment strategy for this devastating disorder.
1. Hawley JS, Weiner WJ. Hemiballismus: current concepts and review. Parkinsonism Relat Disord. 2012;18(2):125‐129. doi:10.1016/j.parkreldis.2011.08.015
2. Gasca-Salas C, Lang AE. Paroxysmal Hemiballism/ Hemichorea Resulting from Transient Ischemic Attacks. Mov Disord Clin Pract. 2015;3(3):303‐305. doi:10.1002/mdc3.12268
3. Garcia-Grimshaw MA, Jimenez-Ruiz A, Ornelas-Velazquez A, Luna-Armenta A, Gutierrez-Manjarrez FA. New-onset diabetes presenting as monoballism secondary to a mixed hyperglycemic crisis. Cureus. 2018;10(6):e2882. doi:10.7759/cureus.2882
4. Postuma RB, Lang AE. Hemiballism: revisiting a classic disorder. Lancet Neurol. 2003;2(11):661‐668. doi:10.1016/s1474-4422(03)00554-4
5. Gallo BV, Shulman LM, Weiner WJ, Petito CK, Berger JR. HIV encephalitis presenting with severe generalized chorea. Neurology. 1996;46(4):1163‐1165. doi:10.1212/wnl.46.4.1163
6. Provenzale JM, Glass JP. Hemiballismus: CT and MR findings. J Comput Assist Tomogr. 1995;19(4):537‐540.
7. Hodde M, Rowe KE, Surapaneni K, Terrigno P, Brighenti A, Altschuler EL. Management of severe hemiballismus: treatment challenges in the acute inpatient rehabilitation setting: a case presentation. PMR. 2017;9(7):732‐735. doi:10.1016/j.pmrj.2016.10.023
8. Laganiere S, Boes AD, Fox MD. Network localization of hemichorea-hemiballismus. Neurology. 2016;86(23):2187‐2195. doi:10.1212/WNL.0000000000002741
9. Cosentino C, Torres L, Nuñez Y, Suarez R, Velez M, Flores M. Hemichorea/hemiballism associated with hyperglycemia: report of 20 cases. Tremor Other Hyperkinet Mov (NY). 2016;6:402. doi:10.7916/D8DN454P
10. Oh SH, Lee KY, Im JH, Lee MS. Chorea associated with non-ketotic hyperglycemia and hyperintensity basal ganglia lesion on T1-weighted brain MRI study: a metaanalysis of 53 cases including four present cases. J Neurol Sci. 2002;200(1-2):57‐62. doi:10.1016/s0022-510x(02)00133-8
11. Carrion DM, Carrion AF. Non-ketotic hyperglycaemia hemichorea-hemiballismus and acute ischaemic stroke. BMJ Case Rep. 2013;2013:bcr2012008359. doi:10.1136/bcr-2012-008359
12. Cho HS, Hong CT, Chan L. Hemichorea after hyperglycemia correction: a case report and a short review of hyperglycemia-related hemichorea at the euglycemic state. Medicine (Baltimore). 2018;97(10):e0076. doi:10.1097/MD.0000000000010076
13. Lin YC, Lin YC. Prolonged hemiballism after the remission of non-ketotic hyperosmolar syndrome. BMJ Case Rep. 2012;2012:bcr0120125627. doi:10.1136/bcr.01.2012.5627
1. Hawley JS, Weiner WJ. Hemiballismus: current concepts and review. Parkinsonism Relat Disord. 2012;18(2):125‐129. doi:10.1016/j.parkreldis.2011.08.015
2. Gasca-Salas C, Lang AE. Paroxysmal Hemiballism/ Hemichorea Resulting from Transient Ischemic Attacks. Mov Disord Clin Pract. 2015;3(3):303‐305. doi:10.1002/mdc3.12268
3. Garcia-Grimshaw MA, Jimenez-Ruiz A, Ornelas-Velazquez A, Luna-Armenta A, Gutierrez-Manjarrez FA. New-onset diabetes presenting as monoballism secondary to a mixed hyperglycemic crisis. Cureus. 2018;10(6):e2882. doi:10.7759/cureus.2882
4. Postuma RB, Lang AE. Hemiballism: revisiting a classic disorder. Lancet Neurol. 2003;2(11):661‐668. doi:10.1016/s1474-4422(03)00554-4
5. Gallo BV, Shulman LM, Weiner WJ, Petito CK, Berger JR. HIV encephalitis presenting with severe generalized chorea. Neurology. 1996;46(4):1163‐1165. doi:10.1212/wnl.46.4.1163
6. Provenzale JM, Glass JP. Hemiballismus: CT and MR findings. J Comput Assist Tomogr. 1995;19(4):537‐540.
7. Hodde M, Rowe KE, Surapaneni K, Terrigno P, Brighenti A, Altschuler EL. Management of severe hemiballismus: treatment challenges in the acute inpatient rehabilitation setting: a case presentation. PMR. 2017;9(7):732‐735. doi:10.1016/j.pmrj.2016.10.023
8. Laganiere S, Boes AD, Fox MD. Network localization of hemichorea-hemiballismus. Neurology. 2016;86(23):2187‐2195. doi:10.1212/WNL.0000000000002741
9. Cosentino C, Torres L, Nuñez Y, Suarez R, Velez M, Flores M. Hemichorea/hemiballism associated with hyperglycemia: report of 20 cases. Tremor Other Hyperkinet Mov (NY). 2016;6:402. doi:10.7916/D8DN454P
10. Oh SH, Lee KY, Im JH, Lee MS. Chorea associated with non-ketotic hyperglycemia and hyperintensity basal ganglia lesion on T1-weighted brain MRI study: a metaanalysis of 53 cases including four present cases. J Neurol Sci. 2002;200(1-2):57‐62. doi:10.1016/s0022-510x(02)00133-8
11. Carrion DM, Carrion AF. Non-ketotic hyperglycaemia hemichorea-hemiballismus and acute ischaemic stroke. BMJ Case Rep. 2013;2013:bcr2012008359. doi:10.1136/bcr-2012-008359
12. Cho HS, Hong CT, Chan L. Hemichorea after hyperglycemia correction: a case report and a short review of hyperglycemia-related hemichorea at the euglycemic state. Medicine (Baltimore). 2018;97(10):e0076. doi:10.1097/MD.0000000000010076
13. Lin YC, Lin YC. Prolonged hemiballism after the remission of non-ketotic hyperosmolar syndrome. BMJ Case Rep. 2012;2012:bcr0120125627. doi:10.1136/bcr.01.2012.5627
How old is too old for statins?
ILLUSTRATIVE CASE
Ms. M is a 76-year-old woman with well-controlled type 2 diabetes mellitus for 10 years and well-controlled mild hypertension. She is otherwise healthy, and her mother lived to age 95. Ms. M has never smoked, has no previous history of vascular/cardiovascular disease, and drinks 1 glass of wine 2 to 3 times per week. Based on the American College of Cardiology (ACC) calculator, she was started on atorvastatin years ago. Is continued use of the medication of any benefit at her current age?
The 2018 American Heart Association (AHA)/ACC/Multi-Society cholesterol guidelines do not provide primary prevention recommendations for those older than age 75 years.3 Up to age 75, the guidelines recommend that patients with type 2 diabetes and a low-density lipoprotein cholesterol (LDL-C) level ≥ 70 mg/dL, as well as those without diabetes but with an LDL-C ≥ 70 mg/dL and a 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥ 10%, be started on medium-intensity statin therapy.
A 2018 consensus panel review of the current literature, sponsored by the National Institute on Aging and the National Heart, Lung, and Blood Institute, concluded that there was insufficient evidence regarding the benefits and harms of statins in older adults, especially those with comorbidities, and that there was a paucity of evidence about statin therapy outcomes (both adverse and beneficial) relevant to older adults.4
A review of all guidelines published since 2013 revealed that only the United Kingdom’s 2014 National Institute for Health and Care Excellence (NICE) guideline provides a strong, risk-based recommendation for initiating primary prevention with statins in patients > 75 years old.5 These recommendations are based on the QRISK2 calculator (which has since been updated to the QRISK3), which assigns everyone ages > 75 years a > 10% 10-year risk score. This provides a universal statin indication for anyone in the 76-to-84 age range.6
Both the ACC/AHA and US Preventive Services Task Force guidelines clearly state that there are too few data and inadequate evidence in people older than 75 for a strong, risk-based statin recommendation.5 The Canadian Cardiovascular Society guideline takes a similar stance, emphasizing that the recommended Framingham risk model is not well validated in people > 75 years.5
STUDY SUMMARIES
Two different looks at statin use in the elderly
A retrospective cohort study (N = 46,864; median follow-up, 5.6 years) examined whether statin treatment is associated with a reduction in atherosclerotic disease and mortality in old and very old adults with and without type 2 diabetes.1 Patients were enrolled from a large, anonymized national database in Spain. The researchers looked only at first-time users of statins and those without a statin prescription within the past 18 months.
Patients with previous ASCVD, type 1 diabetes, previous lipid-lowering treatment, dementia, cancer, or paralysis were excluded, as were those who were in residential care, were on dialysis, or had received an organ transplant. Patients were stratified by age (75-84 years and ≥ 85 years), diabetes status (with or without type 2 diabetes), and statin use (nonuser or new user).
Continue to: Results
Results. For patients with type 2 diabetes, the risk of ASCVD (a composite of coronary heart disease and stroke) was lower among those who took statins than among those who did not in the 75-to-84 group (hazard ratio [HR] = 0.76; 95% confidence interval [CI], 0.65-0.89; 1-year number needed to treat [NNT] = 164). Among those who took statins, there was also lower all-cause mortality (HR = 0.84; 95% CI, 0.75-0.94; 1-year NNT = 306). In those ages ≥ 85 years with diabetes, the statin group did not have a lower risk of ASCVD (HR = 0.82; 95% CI, 0.53-1.26) or all-cause mortality (HR = 1.05; 95% CI, 0.86-1.28).
For patients ages 75 to 84 years without diabetes, there was no difference in risk between groups for ASCVD (HR = 0.94; 95% CI, 0.86–1.04) or all-cause mortality (HR = 0.98; 95% CI, 0.91-1.05). In those ages ≥ 85 years without diabetes, there was also no difference between groups for ASCVD (HR = 1; 95% CI, 0.80-1.24) or for all-cause mortality (HR = 1; 95% CI, 0.90-1.11).
A 2019 meta-analysis of randomized controlled trials (RCTs) (n = 134,537) and RCT summary data (n = 12,705) evaluated the safety and efficacy of statin therapy in patients ages ≥ 55 years.2 In the group of patients ages > 75 years (n = 14,483; median follow-up, 4.9 years), each 1 mmol/L reduction in LDL-C was associated with significant decreased risk for major vascular events (risk ratio [RR] = 0.82; 95% CI, 0.70-0.95) and for major coronary events (RR = 0.82; 95% CI, 0.70-0.96).
In subgroup analysis by the presence or absence of previous vascular disease, there was a decreased risk per 1 mmol/L LDL-C reduction of major vascular events in patients with previous vascular disease (RR = 0.85; 95% CI, 0.73-0.98); however, there was not a significant effect in patients without previous vascular disease (RR = 0.92; 95% CI, 0.73-1.16).
WHAT’S NEW
Statins may be unnecessary in older adults without ASCVD or T2DM
Statin therapy reduces the risk of ASCVD and mortality in patients ages 75 to 84 with type 2 diabetes and in patients > 75 years with known vascular disease. However, statin therapy seems to provide no benefit in patients ages > 75 years without ASCVD or in patients ages ≥ 85 years without ASCVD, regardless of type 2 diabetes status.
Continue to: CAVEATS
CAVEATS
Retrospective cohort design leaves cause and effect equivocal
Even though the first study was large (with more than 46,000 patients) and the median follow-up was 5.6 years, it was a retrospective cohort study. While there is clearly an association between statin therapy and reduced ASCVD and all-cause mortality in patients with diabetes ages 75 to 84 years, cause and effect cannot be unequivocally stated. However, the meta-analysis, which included RCTs, confirms the benefit of statins in secondary prevention for older patients.
The cohort study did not look at adverse effects from statin therapy in this age group, but the data from the 2019 meta-analysis did not reveal any significant risk of myopathy.
CHALLENGES TO IMPLEMENTATION
Guidelines are lacking and discontinuing meds requires discussion
The lack of supporting guidelines to treat this age group with statins remains the largest barrier to implementation. Many patients may already be taking a statin, so a discussion about discontinuing medication will need to be initiated.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Ramos R, Comas-Cufi M, Marti-Lluch R, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ. 2018;362:k3359.
2. Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomized controlled trials. Lancet. 2019;393:407-415.
3. Stone NJ, Grundy SM. The 2018 AHA/ACC/Multi-Society cholesterol guidelines: looking at past, present and future. Prog Cardiovasc Dis. 2019;62:375-383.
4. Singh S, Zieman S, Go AS, et al. Statins for primary prevention in older adults—moving towards evidence-based decision-making. J Am Geriatr Soc. 2018;66:2188-2196.
5. Mortensen MB, Falk E. Primary prevention with statins in the elderly. J Am Coll Cardiol. 2018;71:85-94.
6. ClinRisk. Welcome to the QRISK®3-2018 risk calculator. www.qrisk.org/three/. Accessed May 27, 2020.
ILLUSTRATIVE CASE
Ms. M is a 76-year-old woman with well-controlled type 2 diabetes mellitus for 10 years and well-controlled mild hypertension. She is otherwise healthy, and her mother lived to age 95. Ms. M has never smoked, has no previous history of vascular/cardiovascular disease, and drinks 1 glass of wine 2 to 3 times per week. Based on the American College of Cardiology (ACC) calculator, she was started on atorvastatin years ago. Is continued use of the medication of any benefit at her current age?
The 2018 American Heart Association (AHA)/ACC/Multi-Society cholesterol guidelines do not provide primary prevention recommendations for those older than age 75 years.3 Up to age 75, the guidelines recommend that patients with type 2 diabetes and a low-density lipoprotein cholesterol (LDL-C) level ≥ 70 mg/dL, as well as those without diabetes but with an LDL-C ≥ 70 mg/dL and a 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥ 10%, be started on medium-intensity statin therapy.
A 2018 consensus panel review of the current literature, sponsored by the National Institute on Aging and the National Heart, Lung, and Blood Institute, concluded that there was insufficient evidence regarding the benefits and harms of statins in older adults, especially those with comorbidities, and that there was a paucity of evidence about statin therapy outcomes (both adverse and beneficial) relevant to older adults.4
A review of all guidelines published since 2013 revealed that only the United Kingdom’s 2014 National Institute for Health and Care Excellence (NICE) guideline provides a strong, risk-based recommendation for initiating primary prevention with statins in patients > 75 years old.5 These recommendations are based on the QRISK2 calculator (which has since been updated to the QRISK3), which assigns everyone ages > 75 years a > 10% 10-year risk score. This provides a universal statin indication for anyone in the 76-to-84 age range.6
Both the ACC/AHA and US Preventive Services Task Force guidelines clearly state that there are too few data and inadequate evidence in people older than 75 for a strong, risk-based statin recommendation.5 The Canadian Cardiovascular Society guideline takes a similar stance, emphasizing that the recommended Framingham risk model is not well validated in people > 75 years.5
STUDY SUMMARIES
Two different looks at statin use in the elderly
A retrospective cohort study (N = 46,864; median follow-up, 5.6 years) examined whether statin treatment is associated with a reduction in atherosclerotic disease and mortality in old and very old adults with and without type 2 diabetes.1 Patients were enrolled from a large, anonymized national database in Spain. The researchers looked only at first-time users of statins and those without a statin prescription within the past 18 months.
Patients with previous ASCVD, type 1 diabetes, previous lipid-lowering treatment, dementia, cancer, or paralysis were excluded, as were those who were in residential care, were on dialysis, or had received an organ transplant. Patients were stratified by age (75-84 years and ≥ 85 years), diabetes status (with or without type 2 diabetes), and statin use (nonuser or new user).
Continue to: Results
Results. For patients with type 2 diabetes, the risk of ASCVD (a composite of coronary heart disease and stroke) was lower among those who took statins than among those who did not in the 75-to-84 group (hazard ratio [HR] = 0.76; 95% confidence interval [CI], 0.65-0.89; 1-year number needed to treat [NNT] = 164). Among those who took statins, there was also lower all-cause mortality (HR = 0.84; 95% CI, 0.75-0.94; 1-year NNT = 306). In those ages ≥ 85 years with diabetes, the statin group did not have a lower risk of ASCVD (HR = 0.82; 95% CI, 0.53-1.26) or all-cause mortality (HR = 1.05; 95% CI, 0.86-1.28).
For patients ages 75 to 84 years without diabetes, there was no difference in risk between groups for ASCVD (HR = 0.94; 95% CI, 0.86–1.04) or all-cause mortality (HR = 0.98; 95% CI, 0.91-1.05). In those ages ≥ 85 years without diabetes, there was also no difference between groups for ASCVD (HR = 1; 95% CI, 0.80-1.24) or for all-cause mortality (HR = 1; 95% CI, 0.90-1.11).
A 2019 meta-analysis of randomized controlled trials (RCTs) (n = 134,537) and RCT summary data (n = 12,705) evaluated the safety and efficacy of statin therapy in patients ages ≥ 55 years.2 In the group of patients ages > 75 years (n = 14,483; median follow-up, 4.9 years), each 1 mmol/L reduction in LDL-C was associated with significant decreased risk for major vascular events (risk ratio [RR] = 0.82; 95% CI, 0.70-0.95) and for major coronary events (RR = 0.82; 95% CI, 0.70-0.96).
In subgroup analysis by the presence or absence of previous vascular disease, there was a decreased risk per 1 mmol/L LDL-C reduction of major vascular events in patients with previous vascular disease (RR = 0.85; 95% CI, 0.73-0.98); however, there was not a significant effect in patients without previous vascular disease (RR = 0.92; 95% CI, 0.73-1.16).
WHAT’S NEW
Statins may be unnecessary in older adults without ASCVD or T2DM
Statin therapy reduces the risk of ASCVD and mortality in patients ages 75 to 84 with type 2 diabetes and in patients > 75 years with known vascular disease. However, statin therapy seems to provide no benefit in patients ages > 75 years without ASCVD or in patients ages ≥ 85 years without ASCVD, regardless of type 2 diabetes status.
Continue to: CAVEATS
CAVEATS
Retrospective cohort design leaves cause and effect equivocal
Even though the first study was large (with more than 46,000 patients) and the median follow-up was 5.6 years, it was a retrospective cohort study. While there is clearly an association between statin therapy and reduced ASCVD and all-cause mortality in patients with diabetes ages 75 to 84 years, cause and effect cannot be unequivocally stated. However, the meta-analysis, which included RCTs, confirms the benefit of statins in secondary prevention for older patients.
The cohort study did not look at adverse effects from statin therapy in this age group, but the data from the 2019 meta-analysis did not reveal any significant risk of myopathy.
CHALLENGES TO IMPLEMENTATION
Guidelines are lacking and discontinuing meds requires discussion
The lack of supporting guidelines to treat this age group with statins remains the largest barrier to implementation. Many patients may already be taking a statin, so a discussion about discontinuing medication will need to be initiated.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
ILLUSTRATIVE CASE
Ms. M is a 76-year-old woman with well-controlled type 2 diabetes mellitus for 10 years and well-controlled mild hypertension. She is otherwise healthy, and her mother lived to age 95. Ms. M has never smoked, has no previous history of vascular/cardiovascular disease, and drinks 1 glass of wine 2 to 3 times per week. Based on the American College of Cardiology (ACC) calculator, she was started on atorvastatin years ago. Is continued use of the medication of any benefit at her current age?
The 2018 American Heart Association (AHA)/ACC/Multi-Society cholesterol guidelines do not provide primary prevention recommendations for those older than age 75 years.3 Up to age 75, the guidelines recommend that patients with type 2 diabetes and a low-density lipoprotein cholesterol (LDL-C) level ≥ 70 mg/dL, as well as those without diabetes but with an LDL-C ≥ 70 mg/dL and a 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥ 10%, be started on medium-intensity statin therapy.
A 2018 consensus panel review of the current literature, sponsored by the National Institute on Aging and the National Heart, Lung, and Blood Institute, concluded that there was insufficient evidence regarding the benefits and harms of statins in older adults, especially those with comorbidities, and that there was a paucity of evidence about statin therapy outcomes (both adverse and beneficial) relevant to older adults.4
A review of all guidelines published since 2013 revealed that only the United Kingdom’s 2014 National Institute for Health and Care Excellence (NICE) guideline provides a strong, risk-based recommendation for initiating primary prevention with statins in patients > 75 years old.5 These recommendations are based on the QRISK2 calculator (which has since been updated to the QRISK3), which assigns everyone ages > 75 years a > 10% 10-year risk score. This provides a universal statin indication for anyone in the 76-to-84 age range.6
Both the ACC/AHA and US Preventive Services Task Force guidelines clearly state that there are too few data and inadequate evidence in people older than 75 for a strong, risk-based statin recommendation.5 The Canadian Cardiovascular Society guideline takes a similar stance, emphasizing that the recommended Framingham risk model is not well validated in people > 75 years.5
STUDY SUMMARIES
Two different looks at statin use in the elderly
A retrospective cohort study (N = 46,864; median follow-up, 5.6 years) examined whether statin treatment is associated with a reduction in atherosclerotic disease and mortality in old and very old adults with and without type 2 diabetes.1 Patients were enrolled from a large, anonymized national database in Spain. The researchers looked only at first-time users of statins and those without a statin prescription within the past 18 months.
Patients with previous ASCVD, type 1 diabetes, previous lipid-lowering treatment, dementia, cancer, or paralysis were excluded, as were those who were in residential care, were on dialysis, or had received an organ transplant. Patients were stratified by age (75-84 years and ≥ 85 years), diabetes status (with or without type 2 diabetes), and statin use (nonuser or new user).
Continue to: Results
Results. For patients with type 2 diabetes, the risk of ASCVD (a composite of coronary heart disease and stroke) was lower among those who took statins than among those who did not in the 75-to-84 group (hazard ratio [HR] = 0.76; 95% confidence interval [CI], 0.65-0.89; 1-year number needed to treat [NNT] = 164). Among those who took statins, there was also lower all-cause mortality (HR = 0.84; 95% CI, 0.75-0.94; 1-year NNT = 306). In those ages ≥ 85 years with diabetes, the statin group did not have a lower risk of ASCVD (HR = 0.82; 95% CI, 0.53-1.26) or all-cause mortality (HR = 1.05; 95% CI, 0.86-1.28).
For patients ages 75 to 84 years without diabetes, there was no difference in risk between groups for ASCVD (HR = 0.94; 95% CI, 0.86–1.04) or all-cause mortality (HR = 0.98; 95% CI, 0.91-1.05). In those ages ≥ 85 years without diabetes, there was also no difference between groups for ASCVD (HR = 1; 95% CI, 0.80-1.24) or for all-cause mortality (HR = 1; 95% CI, 0.90-1.11).
A 2019 meta-analysis of randomized controlled trials (RCTs) (n = 134,537) and RCT summary data (n = 12,705) evaluated the safety and efficacy of statin therapy in patients ages ≥ 55 years.2 In the group of patients ages > 75 years (n = 14,483; median follow-up, 4.9 years), each 1 mmol/L reduction in LDL-C was associated with significant decreased risk for major vascular events (risk ratio [RR] = 0.82; 95% CI, 0.70-0.95) and for major coronary events (RR = 0.82; 95% CI, 0.70-0.96).
In subgroup analysis by the presence or absence of previous vascular disease, there was a decreased risk per 1 mmol/L LDL-C reduction of major vascular events in patients with previous vascular disease (RR = 0.85; 95% CI, 0.73-0.98); however, there was not a significant effect in patients without previous vascular disease (RR = 0.92; 95% CI, 0.73-1.16).
WHAT’S NEW
Statins may be unnecessary in older adults without ASCVD or T2DM
Statin therapy reduces the risk of ASCVD and mortality in patients ages 75 to 84 with type 2 diabetes and in patients > 75 years with known vascular disease. However, statin therapy seems to provide no benefit in patients ages > 75 years without ASCVD or in patients ages ≥ 85 years without ASCVD, regardless of type 2 diabetes status.
Continue to: CAVEATS
CAVEATS
Retrospective cohort design leaves cause and effect equivocal
Even though the first study was large (with more than 46,000 patients) and the median follow-up was 5.6 years, it was a retrospective cohort study. While there is clearly an association between statin therapy and reduced ASCVD and all-cause mortality in patients with diabetes ages 75 to 84 years, cause and effect cannot be unequivocally stated. However, the meta-analysis, which included RCTs, confirms the benefit of statins in secondary prevention for older patients.
The cohort study did not look at adverse effects from statin therapy in this age group, but the data from the 2019 meta-analysis did not reveal any significant risk of myopathy.
CHALLENGES TO IMPLEMENTATION
Guidelines are lacking and discontinuing meds requires discussion
The lack of supporting guidelines to treat this age group with statins remains the largest barrier to implementation. Many patients may already be taking a statin, so a discussion about discontinuing medication will need to be initiated.
ACKNOWLEDGMENT
The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.
1. Ramos R, Comas-Cufi M, Marti-Lluch R, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ. 2018;362:k3359.
2. Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomized controlled trials. Lancet. 2019;393:407-415.
3. Stone NJ, Grundy SM. The 2018 AHA/ACC/Multi-Society cholesterol guidelines: looking at past, present and future. Prog Cardiovasc Dis. 2019;62:375-383.
4. Singh S, Zieman S, Go AS, et al. Statins for primary prevention in older adults—moving towards evidence-based decision-making. J Am Geriatr Soc. 2018;66:2188-2196.
5. Mortensen MB, Falk E. Primary prevention with statins in the elderly. J Am Coll Cardiol. 2018;71:85-94.
6. ClinRisk. Welcome to the QRISK®3-2018 risk calculator. www.qrisk.org/three/. Accessed May 27, 2020.
1. Ramos R, Comas-Cufi M, Marti-Lluch R, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ. 2018;362:k3359.
2. Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomized controlled trials. Lancet. 2019;393:407-415.
3. Stone NJ, Grundy SM. The 2018 AHA/ACC/Multi-Society cholesterol guidelines: looking at past, present and future. Prog Cardiovasc Dis. 2019;62:375-383.
4. Singh S, Zieman S, Go AS, et al. Statins for primary prevention in older adults—moving towards evidence-based decision-making. J Am Geriatr Soc. 2018;66:2188-2196.
5. Mortensen MB, Falk E. Primary prevention with statins in the elderly. J Am Coll Cardiol. 2018;71:85-94.
6. ClinRisk. Welcome to the QRISK®3-2018 risk calculator. www.qrisk.org/three/. Accessed May 27, 2020.
PRACTICE CHANGER
Do not start a statin in patients ages ≥ 75 years who do not have known vascular disease or type 2 diabetes; start or continue a statin in all patients ages 75 to 84 with type 2 diabetes to prevent cardiovascular events and mortality; and start or continue a statin in patients ages > 75 years who have known vascular occlusive disease.
STRENGTH OF RECOMMENDATION
B: Based on a meta-analysis of randomized controlled trials and a retrospective cohort study.
Ramos R, Comas-Cufi M, Marti-Lluch R, et al. Statins for primary prevention of cardiovascular events and mortality in old and very old adults with and without type 2 diabetes: retrospective cohort study. BMJ. 2018;362:k3359.1
Cholesterol Treatment Trialists’ Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomized controlled trials. Lancet. 2019;393:407-415.2
First-in-class antipsychotic linked to lower cardiometabolic risk
A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.
A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.
A recently approved first-in-class antipsychotic appears to have fewer adverse cardiometabolic effects than standard care with risperidone, new research suggests.
In post hoc analyses of two short-term randomized controlled trials plus an open-label long-term study, patients with schizophrenia on lumateperone (Caplyta, Intra-Cellular Therapies) had reduced rates of metabolic syndrome, compared with their counterparts taking placebo or the antipsychotic risperidone.
In the short-term studies, rates of metabolic syndrome were similar between groups at baseline, but by the end of 4 and 6 weeks of treatment, 25% of patients taking lumateperone no longer met criteria for metabolic syndrome. A similar finding occurred in 36% of patients in the 1-year open label study.
“One of the major advantages that we found during the drug’s development was that it has a very favorable profile with regard to changes in weight, and other [parameters] associated with cardiovascular disease risk, such as elevated glucose and lipids,” study investigator Andrew Satlin, MD, chief medical officer at Intra-Cellular Therapies, New York, told this news organization.
“So we went back to our data and looked to see whether the changes that we saw had an impact on either the development or the resolution of metabolic syndrome in the patients who came into our studies,” he said.
The findings were presented at the American Society of Clinical Psychopharmacology 2020 Virtual Conference.
Reduced cholesterol
Lumateperone was approved in December by the Food and Drug Administration. The drug acts synergistically through the serotonergic, dopaminergic, and glutamatergic systems.
The short-term studies included 511 patients randomly assigned to receive lumateperone 42 mg (n = 256 patients) or risperidone 4 mg (n = 255 patients).
At baseline, rates of metabolic syndrome were 16% in the lumateperone group and 19% in the risperidone group. At the end of treatment, metabolic syndrome was less common in the lumateperone group (13%) vs. those receiving risperidone (25%).
In addition, 46% of lumateperone patients with metabolic syndrome at baseline no longer had it at the end of the study period. This compared with 25% of patients on risperidone.
The differences in metabolic syndrome conversion rates appeared to be driven by greater reductions in total cholesterol with lumateperone, compared with risperidone (–2.8 mg/dL with lumateperone vs. 4.8 mg/dL with risperidone) and triglycerides (–0.7 mg/dL with lumateperone vs. 20.4 mg/dL with risperidone).
Greater increases in blood glucose were also seen with risperidone (7.7 mg/dL) than with lumateperone (0.9 mg/dL).
The long-term study included 602 patients with stable schizophrenia. All received lumateperone 42 mg, and 197 patients (33%) had metabolic syndrome at baseline.
At the end of the 1-year study, 72 of these patients (36%) no longer met criteria for metabolic syndrome.
“Safest antipsychotic so far”
“Lumateperone seems to be the safest antipsychotic we have seen so far,” Christoph U. Correll, MD, professor of child and adolescent psychiatry, Charité Universitatsmedizin, Berlin, who was also involved in clinical trials of lumateperone, told this news organization.
“It seems to be very safe when it comes to cardiometabolic parameters, and it shows similar reduction in symptoms as risperidone. It is certainly an agent one should consider, particularly when a patient cannot tolerate other medications or may not be in full adherence,” said Dr. Correll, who has a joint appointment as professor of psychiatry and molecular medicine at the Zucker School of Medicine at Hofstra University in Hempstead, New York.
The drug’s safety and efficacy profile would make it a good candidate in patients initiating antipsychotic treatment, but reimbursement issues may be a barrier, at least for now, he added.
He said that the drug may prevent the onset of metabolic side effects and added that once payers are willing to reimburse the drug it should become the “first-line standard of care.”
It is well known that atypical antipsychotics are associated with adverse and rapid metabolic changes. Dr. Correll noted that particularly early-phase and first-episode patients can be “very sensitive” to the side effects of these drugs and often experience rapid weight gain and other adverse metabolic changes. Lumateperone, he added, may help avoid some of this cardiometabolic risk.
Time will tell
Jessica M. Gannon, MD, a psychiatrist at the University of Pittsburgh said in commenting on the findings that the drug’s favorable metabolic profile has previously been reported.
She also noted that there has been some interest in lumateperone because of possible “downstream effects on NMDA-type glutamate receptor activity, a larger binding ratio at dopamine-2:5HT1A receptors than other atypical antipsychotics, and presynaptic D2 partial agonism and a postsynaptic D2 antagonism.”
“This latter feature may explain the reported low extrapyramidal symptom incidence in the clinical trials,” she said .
“While I think future studies and clinical use can help determine how clinically efficacious this medication will be for our patients when compared to others on the market, its favorable metabolic and EPS profile do make it of interest,” added Gannon, who was not involved in researching the drug.
The study was funded by Intra-Cellular Therapies. Dr. Satlin is chief medical officer of Intracellular Therapies. Dr. Correll has been a consultant or advisor to and has received honoraria from Acadia, Alkermes, Allergan, Angelini, Axsome, Gedeon Richter, Gerson Lehrman Group, Intra-Cellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva.
A version of this article originally appeared on Medscape.com.