User login
Machine learning–derived risk score predicts heart failure risk in diabetes patients
PHILADELPHIA – For patients with high-risk diabetes, a novel, machine learning–derived risk score based on 10 common clinical variables can identify those facing a heart failure risk of up to nearly 20% over the ensuing 5 years, an investigator said at the annual meeting of the Heart Failure Society of America.
The risk score, dubbed WATCH-DM, has greater accuracy in predicting incident heart failure than traditional risk-based models, and requires no specific cardiovascular biomarkers or imaging, according to Muthiah Vaduganathan, MD, MPH, a cardiologist at Brigham and Women’s Hospital and faculty at Harvard Medical School in Boston.
The tool may help inform risk-based monitoring and introduction of sodium-glucose transporter 2 (SGLT2) inhibitors, which have been shown in multiple clinical trials to prevent heart failure in at-risk patients with type 2 diabetes mellitus (T2DM), Dr. Vaduganathan said.
“Patients identified at high risk based on WATCH-DM should be strongly considered for initiation of SGLT2 inhibitors in clinical practice,” Dr. Vaduganathan said in an interview.
WATCH-DM is available online at cvriskscores.com. Work is underway to integrate the tool into electronic health record systems at Brigham and Women’s Hospital and at the University of Texas Southwestern Medical Center in Dallas. “I expect that to be launched in the next year,” he said.
The WATCH-DM score was developed based on data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, including 8,756 T2DM patients with inadequate glycemic control at high cardiovascular risk and no heart failure at baseline.
Starting with 147 variables, the investigators used a decision-tree machine learning approach to identify predictors of heart failure.
“What machine learning does is automate the variable selection process, as a form of artificial intelligence,” Dr. Vaduganathan said.
The WATCH-DM risk score was based on the 10 best-performing predictors as selected by machine learning, including body mass index, age, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, serum creatinine, high-density lipoprotein cholesterol, QRS duration, prior myocardial infarction, and prior coronary artery bypass grafting.
The 5-year risk of heart failure was just 1.1% for patients with WATCH-DM scores in the lowest quintile, increasing in a graded fashion to nearly 20% (17.4%) in the highest quintile, study results show.
Findings of the study were simultaneously published in the journal Diabetes Care.
Dr. Vaduganathan said he is supported by an award from Harvard Catalyst. He provided disclosures related to Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim (advisory boards), and with Novartis and the National Institutes of Health (participation on clinical endpoint committees).
SOURCE: HFSA 2019; Segar MW, Vaduganathan M et al. Diabetes Care. doi: 10.2337/dc19-0587.
PHILADELPHIA – For patients with high-risk diabetes, a novel, machine learning–derived risk score based on 10 common clinical variables can identify those facing a heart failure risk of up to nearly 20% over the ensuing 5 years, an investigator said at the annual meeting of the Heart Failure Society of America.
The risk score, dubbed WATCH-DM, has greater accuracy in predicting incident heart failure than traditional risk-based models, and requires no specific cardiovascular biomarkers or imaging, according to Muthiah Vaduganathan, MD, MPH, a cardiologist at Brigham and Women’s Hospital and faculty at Harvard Medical School in Boston.
The tool may help inform risk-based monitoring and introduction of sodium-glucose transporter 2 (SGLT2) inhibitors, which have been shown in multiple clinical trials to prevent heart failure in at-risk patients with type 2 diabetes mellitus (T2DM), Dr. Vaduganathan said.
“Patients identified at high risk based on WATCH-DM should be strongly considered for initiation of SGLT2 inhibitors in clinical practice,” Dr. Vaduganathan said in an interview.
WATCH-DM is available online at cvriskscores.com. Work is underway to integrate the tool into electronic health record systems at Brigham and Women’s Hospital and at the University of Texas Southwestern Medical Center in Dallas. “I expect that to be launched in the next year,” he said.
The WATCH-DM score was developed based on data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, including 8,756 T2DM patients with inadequate glycemic control at high cardiovascular risk and no heart failure at baseline.
Starting with 147 variables, the investigators used a decision-tree machine learning approach to identify predictors of heart failure.
“What machine learning does is automate the variable selection process, as a form of artificial intelligence,” Dr. Vaduganathan said.
The WATCH-DM risk score was based on the 10 best-performing predictors as selected by machine learning, including body mass index, age, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, serum creatinine, high-density lipoprotein cholesterol, QRS duration, prior myocardial infarction, and prior coronary artery bypass grafting.
The 5-year risk of heart failure was just 1.1% for patients with WATCH-DM scores in the lowest quintile, increasing in a graded fashion to nearly 20% (17.4%) in the highest quintile, study results show.
Findings of the study were simultaneously published in the journal Diabetes Care.
Dr. Vaduganathan said he is supported by an award from Harvard Catalyst. He provided disclosures related to Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim (advisory boards), and with Novartis and the National Institutes of Health (participation on clinical endpoint committees).
SOURCE: HFSA 2019; Segar MW, Vaduganathan M et al. Diabetes Care. doi: 10.2337/dc19-0587.
PHILADELPHIA – For patients with high-risk diabetes, a novel, machine learning–derived risk score based on 10 common clinical variables can identify those facing a heart failure risk of up to nearly 20% over the ensuing 5 years, an investigator said at the annual meeting of the Heart Failure Society of America.
The risk score, dubbed WATCH-DM, has greater accuracy in predicting incident heart failure than traditional risk-based models, and requires no specific cardiovascular biomarkers or imaging, according to Muthiah Vaduganathan, MD, MPH, a cardiologist at Brigham and Women’s Hospital and faculty at Harvard Medical School in Boston.
The tool may help inform risk-based monitoring and introduction of sodium-glucose transporter 2 (SGLT2) inhibitors, which have been shown in multiple clinical trials to prevent heart failure in at-risk patients with type 2 diabetes mellitus (T2DM), Dr. Vaduganathan said.
“Patients identified at high risk based on WATCH-DM should be strongly considered for initiation of SGLT2 inhibitors in clinical practice,” Dr. Vaduganathan said in an interview.
WATCH-DM is available online at cvriskscores.com. Work is underway to integrate the tool into electronic health record systems at Brigham and Women’s Hospital and at the University of Texas Southwestern Medical Center in Dallas. “I expect that to be launched in the next year,” he said.
The WATCH-DM score was developed based on data from the ACCORD (Action to Control Cardiovascular Risk in Diabetes) trial, including 8,756 T2DM patients with inadequate glycemic control at high cardiovascular risk and no heart failure at baseline.
Starting with 147 variables, the investigators used a decision-tree machine learning approach to identify predictors of heart failure.
“What machine learning does is automate the variable selection process, as a form of artificial intelligence,” Dr. Vaduganathan said.
The WATCH-DM risk score was based on the 10 best-performing predictors as selected by machine learning, including body mass index, age, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, serum creatinine, high-density lipoprotein cholesterol, QRS duration, prior myocardial infarction, and prior coronary artery bypass grafting.
The 5-year risk of heart failure was just 1.1% for patients with WATCH-DM scores in the lowest quintile, increasing in a graded fashion to nearly 20% (17.4%) in the highest quintile, study results show.
Findings of the study were simultaneously published in the journal Diabetes Care.
Dr. Vaduganathan said he is supported by an award from Harvard Catalyst. He provided disclosures related to Amgen, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim (advisory boards), and with Novartis and the National Institutes of Health (participation on clinical endpoint committees).
SOURCE: HFSA 2019; Segar MW, Vaduganathan M et al. Diabetes Care. doi: 10.2337/dc19-0587.
REPORTING FROM HFSA 2019
Semaglutide beats canagliflozin as second-line therapy for type 2 diabetes
BARCELONA – The glucagonlike peptide–1 receptor antagonist semaglutide (Ozempic) produced greater reductions in glycated hemoglobin and body weight than the sodium-glucose cotransporter 2 inhibitor canagliflozin (Invokana) in second-line treatment in patients with type 2 diabetes after metformin and lifestyle modifications, researchers reported at the annual meeting of the European Association for the Study of Diabetes.
The year-long SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) 8 trial comparing semaglutide and canagliflozin is one of the few head-to-head comparisons of the glucagonlike peptide–1 receptor antagonist (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitor classes of drugs.
Findings showed overall changes in HbA1c level from baseline to week 52 of –1.5 percentage points with semaglutide and –1.0 percentage point with canagliflozin, and changes in body weight during the same time of –5.3 kg and –4.2 kg, respectively. The estimated treatment differences were –0.49 percentage points for HbA1c (P less than .001) and –1.06 kg for body weight (P less than .0029).
A significantly higher percentage of patients receiving semaglutide also achieved HbA1c targets at 52 weeks, compared with those receiving canagliflozin: 66.1% versus 45.1%, respectively, achieved the American Diabetes Association’s target of less than 7%, and 52.8% versus 23.6% (P less than .0001) reached the lower target of 6.5% or lower, as set by the American Association of Clinical Endocrinologists.
Furthermore, a significantly higher proportion of patients in the semaglutide arm achieved 10% or more weight loss by the end of the study (22.3% vs. 8.9% in the canagliflozin arm; P less than .0001), with a trend for 5% or greater weight loss favoring semaglutide (51.1% vs. 46.6%, P = .21). A post hoc analysis also showed that patients treated with semaglutide could achieve a weight loss of 15% or more (6.8% vs. 0.9% for canagliflozin, P = .0001).
“SUSTAIN 8 provides clinically relevant information regarding the head-to-head comparison of these two very commonly used glucose-lowering classes [of drugs] as second-line therapy in patients with type 2 diabetes,” lead study author Ildiko Lingvay, MD, said. The findings support the use of semaglutide as an alternative to canagliflozin when treatment intensification after metformin is needed, Dr. Lingvay and coauthors concluded in an article published simultaneously in Lancet Diabetes & Endocrinology (2019 Sep 17. doi: 10.1016/S2213-8587[19]30311-0).
Dr. Lingvay of the University of Texas in Dallas observed that both GLP-1 RAs and SGLT2 inhibitors are recommended as second-line treatment after metformin and lifestyle modifications, particularly when there is a need to minimize the risk for hypoglycemia and weight gain, and there is established cardiovascular disease. Despite their wide endorsement, however, there has really been only one other head-to-head trial that evaluated the two drug classes – the PIONEER 2 study, which compared oral semaglutide and the SGLT2 inhibitor empagliflozin (Jardiance). Another trial, DURATION-8, compared the GLP-1 RA exenatide (Byetta) or the SGLT2 inhibitor dapagliflozin (Farxiga) with an exenatide-dapagliflozin combination, but it did not directly compare the two drug classes.
SUSTAIN 8 was a phase 3b, randomized, double-blind, parallel-group, controlled trial that compared once-weekly subcutaneous semaglutide 1.0 mg and daily oral canagliflozin 300 mg as add-on treatments to metformin in 788 individuals with type 2 diabetes. Participants had to have a starting HbA1c of between 7.0% and 10.0%, to be on a stable dose of metformin, and to have an estimated glomerular filtration rate of 60 mL/min per 1.73 m3 or higher.
Of the 394 patients randomized to semaglutide, 83.3% completed the study treatment and 15.7% discontinued prematurely, most often because of adverse events (9.7%). Of the remaining 394 patients randomized to canagliflozin therapy, 87.1% completed treatment and 12.9% discontinued prematurely, again mostly for adverse events (5.1%).
Overall the rate of any adverse events (76.0% vs. 71.8%) or serious adverse events (4.6% vs. 5.3%) were similar between the semaglutide and canagliflozin groups. As expected, more gastrointestinal side effects were seen in patients treated with semaglutide than in those treated with canagliflozin (46.9% vs. 27.9%), and there were more infections in the canagliflozin group (29.1% vs. 34.5%). Hypoglycemic episodes were “very rare in this population,” Dr. Lingvay reported. Rates of severe or confirmed hypoglycemia were 1.5% and 1.3% for the respective arms.
Other findings of note were improved fasting blood lipids – with greater changes in total serum cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides seen with semaglutide than canagliflozin. Systolic blood pressure dropped in both groups, with a greater change in the canagliflozin than semaglutide group (–5.5 mm Hg vs. –3.5 mm Hg; P = .0452).
In a substudy of SUSTAIN 8 (n = 178), which was reported separately at the meeting, both semaglutide and canagliflozin reduced total fat mass as assessed with whole-body, dual-energy x-ray absorptiometry scanning. The changes in total fat mass from baseline to week 52 were a respective –3.4 kg and –2.6, or 1.4% and 1.2%. Total lean mass changed by a respective –2.3 kg and –1.5 kg (1.2% and 1.1%), and visceral fat mass by –0.2 kg and –0.1 kg (–0.9% and 0.4%). There was no statistical significance between the groups. A post hoc analysis did show, however, that a greater drop in waist circumference might be achieved with semaglutide than with canagliflozin (–4.0 vs. –2.9 cm [–3.9% vs. –2.5%], P = .02).
“Importantly, neither treatment was associated with deleterious body composition changes, such as gains in fat mass or reductions in the total lean mass,” said Rory McCrimmon, MBChB, professor of experimental diabetes and metabolism at the University of Dundee, Scotland, when presenting the substudy findings.
“These findings are consistent with results from other body composition studies with GLP-1 RAs and SGLT2 [inhibitors],”Dr. McCrimmon said, adding that “the positive effects on total fat loss and visceral fat reduction highlight the role of semaglutide and canagliflozin as relevant treatment options for patients with type 2 diabetes.”
Novo Nordisk funded the study. Dr. Lingvay has received consulting fees from Novo Nordisk; research grants from her institution; and grants, personal fees, or both, from other companies not related to the study. Dr. McCrimmon has received personal fees from Novo Nordisk and two other companies.
SOURCES: Lingvay I et al. Lancet Diabetes Endocrinol. 2019 Sep 17. doi: 10.1016/S2213-8587(19)30311-0; McCrimmon RJ et al. EASD 2019, Abstract 54.
BARCELONA – The glucagonlike peptide–1 receptor antagonist semaglutide (Ozempic) produced greater reductions in glycated hemoglobin and body weight than the sodium-glucose cotransporter 2 inhibitor canagliflozin (Invokana) in second-line treatment in patients with type 2 diabetes after metformin and lifestyle modifications, researchers reported at the annual meeting of the European Association for the Study of Diabetes.
The year-long SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) 8 trial comparing semaglutide and canagliflozin is one of the few head-to-head comparisons of the glucagonlike peptide–1 receptor antagonist (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitor classes of drugs.
Findings showed overall changes in HbA1c level from baseline to week 52 of –1.5 percentage points with semaglutide and –1.0 percentage point with canagliflozin, and changes in body weight during the same time of –5.3 kg and –4.2 kg, respectively. The estimated treatment differences were –0.49 percentage points for HbA1c (P less than .001) and –1.06 kg for body weight (P less than .0029).
A significantly higher percentage of patients receiving semaglutide also achieved HbA1c targets at 52 weeks, compared with those receiving canagliflozin: 66.1% versus 45.1%, respectively, achieved the American Diabetes Association’s target of less than 7%, and 52.8% versus 23.6% (P less than .0001) reached the lower target of 6.5% or lower, as set by the American Association of Clinical Endocrinologists.
Furthermore, a significantly higher proportion of patients in the semaglutide arm achieved 10% or more weight loss by the end of the study (22.3% vs. 8.9% in the canagliflozin arm; P less than .0001), with a trend for 5% or greater weight loss favoring semaglutide (51.1% vs. 46.6%, P = .21). A post hoc analysis also showed that patients treated with semaglutide could achieve a weight loss of 15% or more (6.8% vs. 0.9% for canagliflozin, P = .0001).
“SUSTAIN 8 provides clinically relevant information regarding the head-to-head comparison of these two very commonly used glucose-lowering classes [of drugs] as second-line therapy in patients with type 2 diabetes,” lead study author Ildiko Lingvay, MD, said. The findings support the use of semaglutide as an alternative to canagliflozin when treatment intensification after metformin is needed, Dr. Lingvay and coauthors concluded in an article published simultaneously in Lancet Diabetes & Endocrinology (2019 Sep 17. doi: 10.1016/S2213-8587[19]30311-0).
Dr. Lingvay of the University of Texas in Dallas observed that both GLP-1 RAs and SGLT2 inhibitors are recommended as second-line treatment after metformin and lifestyle modifications, particularly when there is a need to minimize the risk for hypoglycemia and weight gain, and there is established cardiovascular disease. Despite their wide endorsement, however, there has really been only one other head-to-head trial that evaluated the two drug classes – the PIONEER 2 study, which compared oral semaglutide and the SGLT2 inhibitor empagliflozin (Jardiance). Another trial, DURATION-8, compared the GLP-1 RA exenatide (Byetta) or the SGLT2 inhibitor dapagliflozin (Farxiga) with an exenatide-dapagliflozin combination, but it did not directly compare the two drug classes.
SUSTAIN 8 was a phase 3b, randomized, double-blind, parallel-group, controlled trial that compared once-weekly subcutaneous semaglutide 1.0 mg and daily oral canagliflozin 300 mg as add-on treatments to metformin in 788 individuals with type 2 diabetes. Participants had to have a starting HbA1c of between 7.0% and 10.0%, to be on a stable dose of metformin, and to have an estimated glomerular filtration rate of 60 mL/min per 1.73 m3 or higher.
Of the 394 patients randomized to semaglutide, 83.3% completed the study treatment and 15.7% discontinued prematurely, most often because of adverse events (9.7%). Of the remaining 394 patients randomized to canagliflozin therapy, 87.1% completed treatment and 12.9% discontinued prematurely, again mostly for adverse events (5.1%).
Overall the rate of any adverse events (76.0% vs. 71.8%) or serious adverse events (4.6% vs. 5.3%) were similar between the semaglutide and canagliflozin groups. As expected, more gastrointestinal side effects were seen in patients treated with semaglutide than in those treated with canagliflozin (46.9% vs. 27.9%), and there were more infections in the canagliflozin group (29.1% vs. 34.5%). Hypoglycemic episodes were “very rare in this population,” Dr. Lingvay reported. Rates of severe or confirmed hypoglycemia were 1.5% and 1.3% for the respective arms.
Other findings of note were improved fasting blood lipids – with greater changes in total serum cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides seen with semaglutide than canagliflozin. Systolic blood pressure dropped in both groups, with a greater change in the canagliflozin than semaglutide group (–5.5 mm Hg vs. –3.5 mm Hg; P = .0452).
In a substudy of SUSTAIN 8 (n = 178), which was reported separately at the meeting, both semaglutide and canagliflozin reduced total fat mass as assessed with whole-body, dual-energy x-ray absorptiometry scanning. The changes in total fat mass from baseline to week 52 were a respective –3.4 kg and –2.6, or 1.4% and 1.2%. Total lean mass changed by a respective –2.3 kg and –1.5 kg (1.2% and 1.1%), and visceral fat mass by –0.2 kg and –0.1 kg (–0.9% and 0.4%). There was no statistical significance between the groups. A post hoc analysis did show, however, that a greater drop in waist circumference might be achieved with semaglutide than with canagliflozin (–4.0 vs. –2.9 cm [–3.9% vs. –2.5%], P = .02).
“Importantly, neither treatment was associated with deleterious body composition changes, such as gains in fat mass or reductions in the total lean mass,” said Rory McCrimmon, MBChB, professor of experimental diabetes and metabolism at the University of Dundee, Scotland, when presenting the substudy findings.
“These findings are consistent with results from other body composition studies with GLP-1 RAs and SGLT2 [inhibitors],”Dr. McCrimmon said, adding that “the positive effects on total fat loss and visceral fat reduction highlight the role of semaglutide and canagliflozin as relevant treatment options for patients with type 2 diabetes.”
Novo Nordisk funded the study. Dr. Lingvay has received consulting fees from Novo Nordisk; research grants from her institution; and grants, personal fees, or both, from other companies not related to the study. Dr. McCrimmon has received personal fees from Novo Nordisk and two other companies.
SOURCES: Lingvay I et al. Lancet Diabetes Endocrinol. 2019 Sep 17. doi: 10.1016/S2213-8587(19)30311-0; McCrimmon RJ et al. EASD 2019, Abstract 54.
BARCELONA – The glucagonlike peptide–1 receptor antagonist semaglutide (Ozempic) produced greater reductions in glycated hemoglobin and body weight than the sodium-glucose cotransporter 2 inhibitor canagliflozin (Invokana) in second-line treatment in patients with type 2 diabetes after metformin and lifestyle modifications, researchers reported at the annual meeting of the European Association for the Study of Diabetes.
The year-long SUSTAIN (Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes) 8 trial comparing semaglutide and canagliflozin is one of the few head-to-head comparisons of the glucagonlike peptide–1 receptor antagonist (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT2) inhibitor classes of drugs.
Findings showed overall changes in HbA1c level from baseline to week 52 of –1.5 percentage points with semaglutide and –1.0 percentage point with canagliflozin, and changes in body weight during the same time of –5.3 kg and –4.2 kg, respectively. The estimated treatment differences were –0.49 percentage points for HbA1c (P less than .001) and –1.06 kg for body weight (P less than .0029).
A significantly higher percentage of patients receiving semaglutide also achieved HbA1c targets at 52 weeks, compared with those receiving canagliflozin: 66.1% versus 45.1%, respectively, achieved the American Diabetes Association’s target of less than 7%, and 52.8% versus 23.6% (P less than .0001) reached the lower target of 6.5% or lower, as set by the American Association of Clinical Endocrinologists.
Furthermore, a significantly higher proportion of patients in the semaglutide arm achieved 10% or more weight loss by the end of the study (22.3% vs. 8.9% in the canagliflozin arm; P less than .0001), with a trend for 5% or greater weight loss favoring semaglutide (51.1% vs. 46.6%, P = .21). A post hoc analysis also showed that patients treated with semaglutide could achieve a weight loss of 15% or more (6.8% vs. 0.9% for canagliflozin, P = .0001).
“SUSTAIN 8 provides clinically relevant information regarding the head-to-head comparison of these two very commonly used glucose-lowering classes [of drugs] as second-line therapy in patients with type 2 diabetes,” lead study author Ildiko Lingvay, MD, said. The findings support the use of semaglutide as an alternative to canagliflozin when treatment intensification after metformin is needed, Dr. Lingvay and coauthors concluded in an article published simultaneously in Lancet Diabetes & Endocrinology (2019 Sep 17. doi: 10.1016/S2213-8587[19]30311-0).
Dr. Lingvay of the University of Texas in Dallas observed that both GLP-1 RAs and SGLT2 inhibitors are recommended as second-line treatment after metformin and lifestyle modifications, particularly when there is a need to minimize the risk for hypoglycemia and weight gain, and there is established cardiovascular disease. Despite their wide endorsement, however, there has really been only one other head-to-head trial that evaluated the two drug classes – the PIONEER 2 study, which compared oral semaglutide and the SGLT2 inhibitor empagliflozin (Jardiance). Another trial, DURATION-8, compared the GLP-1 RA exenatide (Byetta) or the SGLT2 inhibitor dapagliflozin (Farxiga) with an exenatide-dapagliflozin combination, but it did not directly compare the two drug classes.
SUSTAIN 8 was a phase 3b, randomized, double-blind, parallel-group, controlled trial that compared once-weekly subcutaneous semaglutide 1.0 mg and daily oral canagliflozin 300 mg as add-on treatments to metformin in 788 individuals with type 2 diabetes. Participants had to have a starting HbA1c of between 7.0% and 10.0%, to be on a stable dose of metformin, and to have an estimated glomerular filtration rate of 60 mL/min per 1.73 m3 or higher.
Of the 394 patients randomized to semaglutide, 83.3% completed the study treatment and 15.7% discontinued prematurely, most often because of adverse events (9.7%). Of the remaining 394 patients randomized to canagliflozin therapy, 87.1% completed treatment and 12.9% discontinued prematurely, again mostly for adverse events (5.1%).
Overall the rate of any adverse events (76.0% vs. 71.8%) or serious adverse events (4.6% vs. 5.3%) were similar between the semaglutide and canagliflozin groups. As expected, more gastrointestinal side effects were seen in patients treated with semaglutide than in those treated with canagliflozin (46.9% vs. 27.9%), and there were more infections in the canagliflozin group (29.1% vs. 34.5%). Hypoglycemic episodes were “very rare in this population,” Dr. Lingvay reported. Rates of severe or confirmed hypoglycemia were 1.5% and 1.3% for the respective arms.
Other findings of note were improved fasting blood lipids – with greater changes in total serum cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides seen with semaglutide than canagliflozin. Systolic blood pressure dropped in both groups, with a greater change in the canagliflozin than semaglutide group (–5.5 mm Hg vs. –3.5 mm Hg; P = .0452).
In a substudy of SUSTAIN 8 (n = 178), which was reported separately at the meeting, both semaglutide and canagliflozin reduced total fat mass as assessed with whole-body, dual-energy x-ray absorptiometry scanning. The changes in total fat mass from baseline to week 52 were a respective –3.4 kg and –2.6, or 1.4% and 1.2%. Total lean mass changed by a respective –2.3 kg and –1.5 kg (1.2% and 1.1%), and visceral fat mass by –0.2 kg and –0.1 kg (–0.9% and 0.4%). There was no statistical significance between the groups. A post hoc analysis did show, however, that a greater drop in waist circumference might be achieved with semaglutide than with canagliflozin (–4.0 vs. –2.9 cm [–3.9% vs. –2.5%], P = .02).
“Importantly, neither treatment was associated with deleterious body composition changes, such as gains in fat mass or reductions in the total lean mass,” said Rory McCrimmon, MBChB, professor of experimental diabetes and metabolism at the University of Dundee, Scotland, when presenting the substudy findings.
“These findings are consistent with results from other body composition studies with GLP-1 RAs and SGLT2 [inhibitors],”Dr. McCrimmon said, adding that “the positive effects on total fat loss and visceral fat reduction highlight the role of semaglutide and canagliflozin as relevant treatment options for patients with type 2 diabetes.”
Novo Nordisk funded the study. Dr. Lingvay has received consulting fees from Novo Nordisk; research grants from her institution; and grants, personal fees, or both, from other companies not related to the study. Dr. McCrimmon has received personal fees from Novo Nordisk and two other companies.
SOURCES: Lingvay I et al. Lancet Diabetes Endocrinol. 2019 Sep 17. doi: 10.1016/S2213-8587(19)30311-0; McCrimmon RJ et al. EASD 2019, Abstract 54.
REPORTING FROM EASD 2019
FDA approves oral semaglutide for HbA1c management in type 2 diabetes
The Food and Drug Administration has approved semaglutide (Rybelsus) tablets for the treatment of type 2 diabetes in adults who have not met their hemoglobin A1c goal. It is the first glucagonlike peptide–1 (GLP-1) analogue to be approved in pill form in the United States.
The approval was based on results from the PIONEER trials, a series of 10 studies that assessed semaglutide against sitagliptin, empagliflozin, and liraglutide in a total of 9,543 patients with type 2 diabetes. Patients who received semaglutide had reduced hemoglobin A1c levels as well as reduced body weight.
The most common adverse events reported during the PIONEER trials were nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation. The rate of adverse events were similar across trials.
“GLP-1 receptor agonists are effective medications for people with type 2 diabetes but have been underutilized, in part because until now, they have been available only as an injectable treatment. The availability of an oral GLP-1 receptor agonist represents a significant development, and primary care providers, specialists, and patients alike may now be more receptive to the use of a GLP-1 therapy to help them achieve their blood sugar goals,” said Vanita R. Aroda, MD, director of diabetes clinical research at Brigham and Women’s Hospital in Boston and PIONEER clinical trial researcher.
Semaglutide is approved for once-daily use, at doses of 7 mg and 14 mg. Find the full press release on the Novo Nordisk website.
The Food and Drug Administration has approved semaglutide (Rybelsus) tablets for the treatment of type 2 diabetes in adults who have not met their hemoglobin A1c goal. It is the first glucagonlike peptide–1 (GLP-1) analogue to be approved in pill form in the United States.
The approval was based on results from the PIONEER trials, a series of 10 studies that assessed semaglutide against sitagliptin, empagliflozin, and liraglutide in a total of 9,543 patients with type 2 diabetes. Patients who received semaglutide had reduced hemoglobin A1c levels as well as reduced body weight.
The most common adverse events reported during the PIONEER trials were nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation. The rate of adverse events were similar across trials.
“GLP-1 receptor agonists are effective medications for people with type 2 diabetes but have been underutilized, in part because until now, they have been available only as an injectable treatment. The availability of an oral GLP-1 receptor agonist represents a significant development, and primary care providers, specialists, and patients alike may now be more receptive to the use of a GLP-1 therapy to help them achieve their blood sugar goals,” said Vanita R. Aroda, MD, director of diabetes clinical research at Brigham and Women’s Hospital in Boston and PIONEER clinical trial researcher.
Semaglutide is approved for once-daily use, at doses of 7 mg and 14 mg. Find the full press release on the Novo Nordisk website.
The Food and Drug Administration has approved semaglutide (Rybelsus) tablets for the treatment of type 2 diabetes in adults who have not met their hemoglobin A1c goal. It is the first glucagonlike peptide–1 (GLP-1) analogue to be approved in pill form in the United States.
The approval was based on results from the PIONEER trials, a series of 10 studies that assessed semaglutide against sitagliptin, empagliflozin, and liraglutide in a total of 9,543 patients with type 2 diabetes. Patients who received semaglutide had reduced hemoglobin A1c levels as well as reduced body weight.
The most common adverse events reported during the PIONEER trials were nausea, abdominal pain, diarrhea, decreased appetite, vomiting, and constipation. The rate of adverse events were similar across trials.
“GLP-1 receptor agonists are effective medications for people with type 2 diabetes but have been underutilized, in part because until now, they have been available only as an injectable treatment. The availability of an oral GLP-1 receptor agonist represents a significant development, and primary care providers, specialists, and patients alike may now be more receptive to the use of a GLP-1 therapy to help them achieve their blood sugar goals,” said Vanita R. Aroda, MD, director of diabetes clinical research at Brigham and Women’s Hospital in Boston and PIONEER clinical trial researcher.
Semaglutide is approved for once-daily use, at doses of 7 mg and 14 mg. Find the full press release on the Novo Nordisk website.
First data VERIFY value of early combination therapy in type 2 diabetes
BARCELONA – Upfront use of a dual combination of vildagliptin (Galvus) and metformin was associated with better and more durable glycemic control than metformin alone in patients with newly diagnosed type 2 diabetes, according to findings reported at the annual meeting of the European Association for the Study of Diabetes.
Fewer patients treated with the combination than with metformin monotherapy experienced “treatment failure” (43.6% vs. 62.1%, respectively) during the initial study period. The time-to-treatment failure, which was defined as an hemoglobin A1c of at least 7% (53 mmol/L) or higher on two occasions 3 months apart, was estimated to be beyond the study’s duration, at 61·9 months, for the combination and a median of 36.1 months in the monotherapy group.
Moreover, there was a significant (P less than .0001) 49% reduction in the relative risk for the time-to-initial-treatment failure in the early combination treatment group, compared with the monotherapy group, during the 5-year study period. The time-to-second-treatment failure was also longer in patients who received initial combination therapy (hazard ratio, 0.74; P less than .0001).
These results of the VERIFY (Vildagliptin Efficacy in Combination With Metformin for Early Treatment of Type 2 Diabetes) study, which were published simultaneously in the Lancet, provide the first real evidence to support the use of combination therapy rather than the current standard of metformin alone in the initial treatment of type 2 diabetes.
VERIFY was a phase 4, randomized, parallel-group study designed to compare the durability of glycemic control achieved with a combination of vildagliptin plus metformin or metformin alone in treatment-naive patients with type 2 diabetes.
At a press briefing, three members of the VERITY steering committee explained the rationale, design, results, and implications of the study.
EASD president David R. Matthews, DPhil, FRCP, who is emeritus professor at the Oxford Centre for Diabetes, Endocrinology and Metabolism at the University of Oxford (England), observed that the study aimed to answer three important questions: Do patients with type 2 diabetes benefit from having combination treatment from the start of their pharmacologic management, and if so, is this more beneficial than a step-up approach, and ultimately, “does it really matter?”
A typical cohort of patients was included, said Michael Stumvoll, MD, of the University Hospital Leipzig (Germany). Patients had to be aged between 18 and 70 years, have a body mass index of 22-40 kg/m2, and an hemoglobin A1c level of 6.5%-7.5%. This “rather narrow range” was decided “on purpose to really fulfill the idea of having newly diagnosed [type 2 diabetes]”, Dr. Stumvoll noted. In addition, patients had to have adequate renal function, have been diagnosed with type 2 diabetes in the past 2 years, and be drug naive or have received no more than 4 weeks of metformin.
In all, 2,001 patients from 254 centers in 34 countries were included, with 998 randomized to initial treatment with vildagliptin and metformin and 1,003 to receive metformin alone after an initial run-in phase during which the dose of metformin was up-titrated from 500 to 1,500 mg/day. The study ran for 5 years, with treatment intensified if there was a loss of glycemic control at the discretion of the study investigators – first vildagliptin was added to patients taking metformin monotherapy, then insulin, if needed.
There were no safety concerns: A similar percentage of patients in the early combination and initial monotherapy arms experienced an adverse event (83.5% vs. 83.2%, respectively), a serious adverse event (16.6% vs. 18.3%), a drug-related adverse event (15.9% vs. 14.3%), a severe adverse event (10.5% vs. 10.6%), and adverse events leading to discontinuation of treatment (4.1% vs. 5.3%) or death (13 vs. 9 patients). There was no difference in the change in body weight, and rates of hypoglycemia were 1.3% and 0.9%, respectively.
Adjudication and an independent data-monitoring committee were set up after cardiovascular events occurred in a few patients, although this was not a cardiovascular outcomes trials, Dr. Matthews stressed. There were fewer absolute cumulative adjudicated events in the early combination arm, compared with the initial monotherapy arm (30 vs. 44, respectively), and the time to the first adjudicated macrovascular event favored early combination over initial monotherapy (2.4% vs. 3.3%; HR, 0.71).
“There is a big caveat here,” said Dr. Matthews, “these are very small numbers and wide confidence intervals and the P value is .194.” Although “it is not a significant finding, and it was never intended to be a significant finding,” it gives “an indication that we absolutely should be looking at this.”
Stefano Del Prato, MD, of the University of Pisa (Italy), noted that “there has been a lot of discussion around initial combination therapy for type 2 diabetes,” and although there was a realization that multiple treatment might be necessary, there was no evidence for that. The results of the VERIFY trial, however, now provide some of the proof that this approach may be of benefit. Patients “benefit twice as much” with the combination therapy as they do with the monotherapy, Dr. Del Prato said. “There are twice as many patients retained under control with an early combination, compared with the monotherapy.” That means no longer “running after the patient losing control” he said, but “being proactive” and with a very low risk of hypoglycemia. The clinical implication is that there is now evidence for combination therapy as an initial approach for managing type 2 diabetes.
Novartis funded the study. Dr. Matthews has served on advisory boards or as a consultant for, and has given lectures for, Novartis and numerous other companies not related to the study. He is currently the president of the European Association for the Study of Diabetes. Dr. Stumvoll has received speaker's honoraria and consulting fees from Novartis and other companies. Dr. Del Prato serves or has served on advisory boards and speakers bureaus for, and received research support from, Novartis and numerous other companies.
SOURCE: Matthews DR et al. Lancet. 2019 Sept 18. doi: 10.1016/ S0140-6736(19)32131-2.
This article was updated on 9/19/2019.
BARCELONA – Upfront use of a dual combination of vildagliptin (Galvus) and metformin was associated with better and more durable glycemic control than metformin alone in patients with newly diagnosed type 2 diabetes, according to findings reported at the annual meeting of the European Association for the Study of Diabetes.
Fewer patients treated with the combination than with metformin monotherapy experienced “treatment failure” (43.6% vs. 62.1%, respectively) during the initial study period. The time-to-treatment failure, which was defined as an hemoglobin A1c of at least 7% (53 mmol/L) or higher on two occasions 3 months apart, was estimated to be beyond the study’s duration, at 61·9 months, for the combination and a median of 36.1 months in the monotherapy group.
Moreover, there was a significant (P less than .0001) 49% reduction in the relative risk for the time-to-initial-treatment failure in the early combination treatment group, compared with the monotherapy group, during the 5-year study period. The time-to-second-treatment failure was also longer in patients who received initial combination therapy (hazard ratio, 0.74; P less than .0001).
These results of the VERIFY (Vildagliptin Efficacy in Combination With Metformin for Early Treatment of Type 2 Diabetes) study, which were published simultaneously in the Lancet, provide the first real evidence to support the use of combination therapy rather than the current standard of metformin alone in the initial treatment of type 2 diabetes.
VERIFY was a phase 4, randomized, parallel-group study designed to compare the durability of glycemic control achieved with a combination of vildagliptin plus metformin or metformin alone in treatment-naive patients with type 2 diabetes.
At a press briefing, three members of the VERITY steering committee explained the rationale, design, results, and implications of the study.
EASD president David R. Matthews, DPhil, FRCP, who is emeritus professor at the Oxford Centre for Diabetes, Endocrinology and Metabolism at the University of Oxford (England), observed that the study aimed to answer three important questions: Do patients with type 2 diabetes benefit from having combination treatment from the start of their pharmacologic management, and if so, is this more beneficial than a step-up approach, and ultimately, “does it really matter?”
A typical cohort of patients was included, said Michael Stumvoll, MD, of the University Hospital Leipzig (Germany). Patients had to be aged between 18 and 70 years, have a body mass index of 22-40 kg/m2, and an hemoglobin A1c level of 6.5%-7.5%. This “rather narrow range” was decided “on purpose to really fulfill the idea of having newly diagnosed [type 2 diabetes]”, Dr. Stumvoll noted. In addition, patients had to have adequate renal function, have been diagnosed with type 2 diabetes in the past 2 years, and be drug naive or have received no more than 4 weeks of metformin.
In all, 2,001 patients from 254 centers in 34 countries were included, with 998 randomized to initial treatment with vildagliptin and metformin and 1,003 to receive metformin alone after an initial run-in phase during which the dose of metformin was up-titrated from 500 to 1,500 mg/day. The study ran for 5 years, with treatment intensified if there was a loss of glycemic control at the discretion of the study investigators – first vildagliptin was added to patients taking metformin monotherapy, then insulin, if needed.
There were no safety concerns: A similar percentage of patients in the early combination and initial monotherapy arms experienced an adverse event (83.5% vs. 83.2%, respectively), a serious adverse event (16.6% vs. 18.3%), a drug-related adverse event (15.9% vs. 14.3%), a severe adverse event (10.5% vs. 10.6%), and adverse events leading to discontinuation of treatment (4.1% vs. 5.3%) or death (13 vs. 9 patients). There was no difference in the change in body weight, and rates of hypoglycemia were 1.3% and 0.9%, respectively.
Adjudication and an independent data-monitoring committee were set up after cardiovascular events occurred in a few patients, although this was not a cardiovascular outcomes trials, Dr. Matthews stressed. There were fewer absolute cumulative adjudicated events in the early combination arm, compared with the initial monotherapy arm (30 vs. 44, respectively), and the time to the first adjudicated macrovascular event favored early combination over initial monotherapy (2.4% vs. 3.3%; HR, 0.71).
“There is a big caveat here,” said Dr. Matthews, “these are very small numbers and wide confidence intervals and the P value is .194.” Although “it is not a significant finding, and it was never intended to be a significant finding,” it gives “an indication that we absolutely should be looking at this.”
Stefano Del Prato, MD, of the University of Pisa (Italy), noted that “there has been a lot of discussion around initial combination therapy for type 2 diabetes,” and although there was a realization that multiple treatment might be necessary, there was no evidence for that. The results of the VERIFY trial, however, now provide some of the proof that this approach may be of benefit. Patients “benefit twice as much” with the combination therapy as they do with the monotherapy, Dr. Del Prato said. “There are twice as many patients retained under control with an early combination, compared with the monotherapy.” That means no longer “running after the patient losing control” he said, but “being proactive” and with a very low risk of hypoglycemia. The clinical implication is that there is now evidence for combination therapy as an initial approach for managing type 2 diabetes.
Novartis funded the study. Dr. Matthews has served on advisory boards or as a consultant for, and has given lectures for, Novartis and numerous other companies not related to the study. He is currently the president of the European Association for the Study of Diabetes. Dr. Stumvoll has received speaker's honoraria and consulting fees from Novartis and other companies. Dr. Del Prato serves or has served on advisory boards and speakers bureaus for, and received research support from, Novartis and numerous other companies.
SOURCE: Matthews DR et al. Lancet. 2019 Sept 18. doi: 10.1016/ S0140-6736(19)32131-2.
This article was updated on 9/19/2019.
BARCELONA – Upfront use of a dual combination of vildagliptin (Galvus) and metformin was associated with better and more durable glycemic control than metformin alone in patients with newly diagnosed type 2 diabetes, according to findings reported at the annual meeting of the European Association for the Study of Diabetes.
Fewer patients treated with the combination than with metformin monotherapy experienced “treatment failure” (43.6% vs. 62.1%, respectively) during the initial study period. The time-to-treatment failure, which was defined as an hemoglobin A1c of at least 7% (53 mmol/L) or higher on two occasions 3 months apart, was estimated to be beyond the study’s duration, at 61·9 months, for the combination and a median of 36.1 months in the monotherapy group.
Moreover, there was a significant (P less than .0001) 49% reduction in the relative risk for the time-to-initial-treatment failure in the early combination treatment group, compared with the monotherapy group, during the 5-year study period. The time-to-second-treatment failure was also longer in patients who received initial combination therapy (hazard ratio, 0.74; P less than .0001).
These results of the VERIFY (Vildagliptin Efficacy in Combination With Metformin for Early Treatment of Type 2 Diabetes) study, which were published simultaneously in the Lancet, provide the first real evidence to support the use of combination therapy rather than the current standard of metformin alone in the initial treatment of type 2 diabetes.
VERIFY was a phase 4, randomized, parallel-group study designed to compare the durability of glycemic control achieved with a combination of vildagliptin plus metformin or metformin alone in treatment-naive patients with type 2 diabetes.
At a press briefing, three members of the VERITY steering committee explained the rationale, design, results, and implications of the study.
EASD president David R. Matthews, DPhil, FRCP, who is emeritus professor at the Oxford Centre for Diabetes, Endocrinology and Metabolism at the University of Oxford (England), observed that the study aimed to answer three important questions: Do patients with type 2 diabetes benefit from having combination treatment from the start of their pharmacologic management, and if so, is this more beneficial than a step-up approach, and ultimately, “does it really matter?”
A typical cohort of patients was included, said Michael Stumvoll, MD, of the University Hospital Leipzig (Germany). Patients had to be aged between 18 and 70 years, have a body mass index of 22-40 kg/m2, and an hemoglobin A1c level of 6.5%-7.5%. This “rather narrow range” was decided “on purpose to really fulfill the idea of having newly diagnosed [type 2 diabetes]”, Dr. Stumvoll noted. In addition, patients had to have adequate renal function, have been diagnosed with type 2 diabetes in the past 2 years, and be drug naive or have received no more than 4 weeks of metformin.
In all, 2,001 patients from 254 centers in 34 countries were included, with 998 randomized to initial treatment with vildagliptin and metformin and 1,003 to receive metformin alone after an initial run-in phase during which the dose of metformin was up-titrated from 500 to 1,500 mg/day. The study ran for 5 years, with treatment intensified if there was a loss of glycemic control at the discretion of the study investigators – first vildagliptin was added to patients taking metformin monotherapy, then insulin, if needed.
There were no safety concerns: A similar percentage of patients in the early combination and initial monotherapy arms experienced an adverse event (83.5% vs. 83.2%, respectively), a serious adverse event (16.6% vs. 18.3%), a drug-related adverse event (15.9% vs. 14.3%), a severe adverse event (10.5% vs. 10.6%), and adverse events leading to discontinuation of treatment (4.1% vs. 5.3%) or death (13 vs. 9 patients). There was no difference in the change in body weight, and rates of hypoglycemia were 1.3% and 0.9%, respectively.
Adjudication and an independent data-monitoring committee were set up after cardiovascular events occurred in a few patients, although this was not a cardiovascular outcomes trials, Dr. Matthews stressed. There were fewer absolute cumulative adjudicated events in the early combination arm, compared with the initial monotherapy arm (30 vs. 44, respectively), and the time to the first adjudicated macrovascular event favored early combination over initial monotherapy (2.4% vs. 3.3%; HR, 0.71).
“There is a big caveat here,” said Dr. Matthews, “these are very small numbers and wide confidence intervals and the P value is .194.” Although “it is not a significant finding, and it was never intended to be a significant finding,” it gives “an indication that we absolutely should be looking at this.”
Stefano Del Prato, MD, of the University of Pisa (Italy), noted that “there has been a lot of discussion around initial combination therapy for type 2 diabetes,” and although there was a realization that multiple treatment might be necessary, there was no evidence for that. The results of the VERIFY trial, however, now provide some of the proof that this approach may be of benefit. Patients “benefit twice as much” with the combination therapy as they do with the monotherapy, Dr. Del Prato said. “There are twice as many patients retained under control with an early combination, compared with the monotherapy.” That means no longer “running after the patient losing control” he said, but “being proactive” and with a very low risk of hypoglycemia. The clinical implication is that there is now evidence for combination therapy as an initial approach for managing type 2 diabetes.
Novartis funded the study. Dr. Matthews has served on advisory boards or as a consultant for, and has given lectures for, Novartis and numerous other companies not related to the study. He is currently the president of the European Association for the Study of Diabetes. Dr. Stumvoll has received speaker's honoraria and consulting fees from Novartis and other companies. Dr. Del Prato serves or has served on advisory boards and speakers bureaus for, and received research support from, Novartis and numerous other companies.
SOURCE: Matthews DR et al. Lancet. 2019 Sept 18. doi: 10.1016/ S0140-6736(19)32131-2.
This article was updated on 9/19/2019.
REPORTING FROM EASD 2019
Dapagliflozin given Fast Track status for HF therapy
The decision is based on results from two phase 3 trials – DAPA-HF and DELIVER – that assessed dapagliflozin in patients with HFrEF and HFpEF, respectively.
Dapagliflozin, an oral, once-daily sodium-glucose transporter 2 inhibitor, was first approved as monotherapy and as part of combination therapy for the improvement of glycemic control in adults with type 2 diabetes. It was also granted Fast Track designation in August 2019 as a therapy for chronic renal disease, both to slow progression of renal failure and to prevent cardiovascular and renal death.
“Heart failure affects approximately 64 million people worldwide, and about half will die within 5 years of diagnosis,” Mene Pangalos, executive vice president of biopharmaceuticals research and development, said in the AstraZeneca press release. “This Fast Track designation for Farxiga brings us closer to fulfilling our ambition to help prevent, treat and cure heart failure, and we look forward to working with the FDA to explore Farxiga as a potential new treatment option for heart failure patients.”
The decision is based on results from two phase 3 trials – DAPA-HF and DELIVER – that assessed dapagliflozin in patients with HFrEF and HFpEF, respectively.
Dapagliflozin, an oral, once-daily sodium-glucose transporter 2 inhibitor, was first approved as monotherapy and as part of combination therapy for the improvement of glycemic control in adults with type 2 diabetes. It was also granted Fast Track designation in August 2019 as a therapy for chronic renal disease, both to slow progression of renal failure and to prevent cardiovascular and renal death.
“Heart failure affects approximately 64 million people worldwide, and about half will die within 5 years of diagnosis,” Mene Pangalos, executive vice president of biopharmaceuticals research and development, said in the AstraZeneca press release. “This Fast Track designation for Farxiga brings us closer to fulfilling our ambition to help prevent, treat and cure heart failure, and we look forward to working with the FDA to explore Farxiga as a potential new treatment option for heart failure patients.”
The decision is based on results from two phase 3 trials – DAPA-HF and DELIVER – that assessed dapagliflozin in patients with HFrEF and HFpEF, respectively.
Dapagliflozin, an oral, once-daily sodium-glucose transporter 2 inhibitor, was first approved as monotherapy and as part of combination therapy for the improvement of glycemic control in adults with type 2 diabetes. It was also granted Fast Track designation in August 2019 as a therapy for chronic renal disease, both to slow progression of renal failure and to prevent cardiovascular and renal death.
“Heart failure affects approximately 64 million people worldwide, and about half will die within 5 years of diagnosis,” Mene Pangalos, executive vice president of biopharmaceuticals research and development, said in the AstraZeneca press release. “This Fast Track designation for Farxiga brings us closer to fulfilling our ambition to help prevent, treat and cure heart failure, and we look forward to working with the FDA to explore Farxiga as a potential new treatment option for heart failure patients.”
NICE issues recommendation for dapagliflozin-insulin therapy in type 1 diabetes
The inadequately controlled by insulin alone.
In a review of clinical trials, NICE found that dapagliflozin plus insulin conferred small benefits in hemoglobin A1c, weight loss, and quality of life, compared with insulin alone. These benefits translated to a reduced risk of long-term complications over the lifetime of the patient.
In the new NICE guideline, dual treatment with dapagliflozin and insulin in adults with type 1 diabetes and a body mass index greater than 27 kg/m2 is recommended only when they are receiving insulin doses of more than 0.5 units/kg per day; have undergone an evidence-based, quality-assured education program; and are supervised by a physician specializing in endocrinology and diabetes.
Hemoglobin A1c levels should be assessed after 6 months and at regular intervals after that; if glycemic control is not improved, dapagliflozin should be stopped, as there is an increased risk of diabetic ketoacidosis.
Find the full technology appraisal guidance on the NICE website.
The inadequately controlled by insulin alone.
In a review of clinical trials, NICE found that dapagliflozin plus insulin conferred small benefits in hemoglobin A1c, weight loss, and quality of life, compared with insulin alone. These benefits translated to a reduced risk of long-term complications over the lifetime of the patient.
In the new NICE guideline, dual treatment with dapagliflozin and insulin in adults with type 1 diabetes and a body mass index greater than 27 kg/m2 is recommended only when they are receiving insulin doses of more than 0.5 units/kg per day; have undergone an evidence-based, quality-assured education program; and are supervised by a physician specializing in endocrinology and diabetes.
Hemoglobin A1c levels should be assessed after 6 months and at regular intervals after that; if glycemic control is not improved, dapagliflozin should be stopped, as there is an increased risk of diabetic ketoacidosis.
Find the full technology appraisal guidance on the NICE website.
The inadequately controlled by insulin alone.
In a review of clinical trials, NICE found that dapagliflozin plus insulin conferred small benefits in hemoglobin A1c, weight loss, and quality of life, compared with insulin alone. These benefits translated to a reduced risk of long-term complications over the lifetime of the patient.
In the new NICE guideline, dual treatment with dapagliflozin and insulin in adults with type 1 diabetes and a body mass index greater than 27 kg/m2 is recommended only when they are receiving insulin doses of more than 0.5 units/kg per day; have undergone an evidence-based, quality-assured education program; and are supervised by a physician specializing in endocrinology and diabetes.
Hemoglobin A1c levels should be assessed after 6 months and at regular intervals after that; if glycemic control is not improved, dapagliflozin should be stopped, as there is an increased risk of diabetic ketoacidosis.
Find the full technology appraisal guidance on the NICE website.
Poll: How much has the price of insulin risen in the past 15 years?
Choose your answer in the poll below. To check the accuracy of your answer, see Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.
[polldaddy:10400221]
Click on page 2 below to find out what the correct answer is...
The correct answer is d.) 500%
To learn more, see this month's Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.
Choose your answer in the poll below. To check the accuracy of your answer, see Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.
[polldaddy:10400221]
Click on page 2 below to find out what the correct answer is...
The correct answer is d.) 500%
To learn more, see this month's Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.
Choose your answer in the poll below. To check the accuracy of your answer, see Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.
[polldaddy:10400221]
Click on page 2 below to find out what the correct answer is...
The correct answer is d.) 500%
To learn more, see this month's Endocrine Consult: 10 (Safe) Ways to Reduce Patients’ Insulin Costs.
10 (Safe) Ways to Reduce Patients’ Insulin Costs
Almost a century after its discovery, insulin remains a life-saving yet costly medication: In the past 15 years, prices have risen more than 500%.1 Patients may ask you why the insulin you prescribe is so expensive, and the complex process for determining drug costs makes it difficult to answer. But the bottom line is, patients need their insulin—and they want it without breaking the bank.
Thankfully, there are several strategies for reducing the cost of insulin. First and foremost, patients must be advised that not taking their prescribed insulin, or taking less insulin than prescribed, is not a safe alternative. An individualized cost-benefit analysis between patient and provider can help to determine the best option for each patient. After working in endocrinology for 5 years, I have learned the following 10 ways to help patients whose financial situations limit their access to insulin.
1 Try older insulins, including mixed insulin 70/30 or 50/50, insulin NPH, or regular insulin. Because the beneficial effects may not be as long lasting with these as with newer insulins on the market, your patient may need to test glucose levels more frequently. Also, insulin NPH and any mixed insulins are suspensions, not solutions, so patients will need to gently roll older insulins prior to use. Those in pen form may also have a shorter shelf life.
2 Switch to a syringe and vial. Although dosing can be less precise, this could be a viable option for patients with good vision and dexterity. This method helps patients save in 3 ways: (1) the insulin is less expensive; (2) syringes generally cost less (about $30 for 100) than pen needle tips (about $50 for 100); and (3) vials of NPH are longer-lasting suspensions that are stable for about 28 days once opened, compared to 14 days for pens.2-4
3 Switch from a 30- to a 90-day supply of refills. This helps to lower copays. For example, a mail-order program (eg, Express Scripts) that ships from a warehouse typically offers lower pricing than a brick-and-mortar pharmacy with greater overhead. Many of these programs provide 2-pharmacist verification for accuracy and free home delivery of medications at a 10% discount, as well as 24-hour pharmacist access.5 The ease of obtaining prescriptions by this method also can help with medication adherence.
4 Patient assistance programs (PAPs) offered by insulin manufacturers can help lower costs for patients who find it difficult to afford their medication. Information on these programs is available on the respective company’s websites, usually in multiple languages (although some are limited to English and Spanish). Patients applying for a PAP must provide a proof of income and adhere to the program’s specific criteria. Renewal is typically required each year.6-8
5 Copay cards are available to many patients with private insurance and may help make insulin more affordable. Patients may be able to receive a $25 monthly supply of insulin for up to 1 year (specific terms vary). Maximum contributions and contributions toward deductibles also vary by program, so patients need to familiarize themselves with what their particular copay card allows. Generally, copay cards are not a sustainable long-term solution; for one thing, they expire, and for another, emphasis should be placed on affordable medications rather than affording expensive medications.
[polldaddy:10400221]
Continue to: 6 External PAPs for patients on Medicare...
6 External PAPs for patients on Medicare can help lower the costs of prescription medications.9 A database of pharmaceutical PAPs is available on the Medicare website.10 Some PAPs may help patients on Medicare pay through the $5,100 coverage gap or “donut hole”—a term referring to a gap in prescription drug coverage once patients have met their prescription limit (all Medicare part D plans have a donut hole).11,12 Patients and providers will need to read the fine print when applying for an external PAP, because some have a monthly or one-time start-up fee for processing the paperwork (and note, there is often paperwork for the relief program in addition to the PAP paperwork through the pharmaceutical company).
7 A Program of All-Inclusive Care for the Elderly (PACE) is available in many states; check medicare.gov to see if your state is eligible. For patients 55 and older on Medicare or Medicaid who do not opt for care at a nursing home facility, PACE may be able to provide care and coverage in the patient’s home or at a PACE facility. Services include primary care, hospital care, laboratory and x-ray services, medical specialty services, and prescription drugs. To be eligible for PACE services, the patient must live in the service area of a PACE organization and have a requirement for a nursing home-level of care (as certified by your state).
8 Shop around for the best deal. Encourage your patients to comparison shop for the best prices rather than accepting the first or only option at their usual pharmacy. Different pharmacies offer drugs at lower prices than competitors. Also, continually compare prices at GoodRx or HealthWarehouse.com. The latter—a fully licensed Internet-based pharmacy—sells FDA-approved medications at affordable prices in all 50 states, without the requirement for insurance coverage.
9 Use of a patch pump may be less expensive for patients with type 2 diabetes who are taking basal-bolus regimens. Patches slowly deliver single short-acting insulin (usually insulin aspart or lispro) that acts as a basal insulin, with an additional reservoir for prandial insulin at mealtime and for snacks. As there is a catheter in the patch, patients would not require the use of needles.13
10 Try removing mealtime insulin for patients with type 2 diabetes who need minimal mealtime insulin. Clinicians can initiate a safe trial of this removal by encouraging the patient to consume a low-carbohydrate diet, increase exercise, and/or use other noninsulin medications that are more affordable.
Continue to: The affordability of insulins...
The affordability of insulins is a potentially uncomfortable but necessary conversation to have with your patient. Providers are one of the best resources for patients who seek relief from financial difficulties. The recommendations discussed here can help providers and patients design a cost-conscious plan for insulin treatment. Although each recommendation is viable, the pros and cons must be weighed on a case-by-case basis. Providers and patients should also pay attention to the Senate Finance Committee’s ongoing discussions and possible resolutions that could result in lower insulin costs. Until legislation that lowers the prices of insulin comes to fruition, however, providers should continue to plan with their patients on how to best get their insulin at the lowest cost.
Test yourself with the poll here.
1. Grassley, Wyden launch bipartisan investigation into insulin prices. United States Senate Committee on Finance website. www.finance.senate.gov/chairmans-news/grassley-wyden-launch-bipartisan-investigation-into-insulin-prices. Published February 22, 2019. Accessed August 16, 2019.
2. BD Ultra-Fine. Syringe. GoodRx website. www.goodrx.com/bd-ultra-fine?dosage=31-gauge-5-16%22-of-1-cc&form=syringe&label_override=BD+Ultra-Fine&quantity=100. Accessed August 16, 2019.
3. BD Ultra-Fine. Pen needle. GoodRx website. www.goodrx.com/bd-ultra-fine?dosage=5-32%22-of-32-gauge&form=pen-needle&label_override=BD+Ultra-Fine&quantity=100. Accessed August 16, 2019.
4. Joffee D. Stability of common insulins in pens and vials. Diabetes in Control website. www.diabetesincontrol.com/wp-content/uploads/PDF/se_insulin_stability_chart.pdf. Published September 2011. Accessed August 16, 2019.
5. Frequently asked questions. Preferred home delivery program for maintenance medications. Express Scripts website. www.express-scripts.com/art/pdf/SST-custom-preferred-faq.pdf. Accessed August 16, 2019.
6. Patient Connection. Sanofi Patient Connection website. www.sanofipatientconnection.com/. Accessed August 16, 2019.
7. The Lilly Cares Foundation Patient Assistance Program. Lilly website. www.lillycares.com/assistanceprograms.aspx. Accessed August 16, 2019.
8. Novo Nordisk Patient Assistance Program. NovoCare website. www.novocare.com/psp/PAP.html. Accessed August 16, 2019.
9. 6 ways to get help with prescription costs. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/costs-in-the-coverage-gap/6-ways-to-get-help-with-prescription-costs. Accessed August 16, 2019.
10. Pharmaceutical assistance program. Medicare website. www.medicare.gov/pharmaceutical-assistance-program/Index.aspx. Accessed August 16, 2019.
11. Catastrophic coverage. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/catastrophic-coverage. Accessed August 16, 2019.
12. Costs in the coverage gap. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/costs-in-the-coverage-gap. Accessed August 16, 2019.
13. V-Go Reimbursement Assistance Program. V-Go website. www.go-vgo.com/coverage-savings/overview/. Accessed August 16, 2019.
Clinician Reviews in partnership with
Alyssa Kanagaki Greenleaf practices at Hartford Healthcare Medical Group Endocrinology in Southington and New Britain, Connecticut.
Clinician Reviews in partnership with
Alyssa Kanagaki Greenleaf practices at Hartford Healthcare Medical Group Endocrinology in Southington and New Britain, Connecticut.
Clinician Reviews in partnership with
Alyssa Kanagaki Greenleaf practices at Hartford Healthcare Medical Group Endocrinology in Southington and New Britain, Connecticut.
Almost a century after its discovery, insulin remains a life-saving yet costly medication: In the past 15 years, prices have risen more than 500%.1 Patients may ask you why the insulin you prescribe is so expensive, and the complex process for determining drug costs makes it difficult to answer. But the bottom line is, patients need their insulin—and they want it without breaking the bank.
Thankfully, there are several strategies for reducing the cost of insulin. First and foremost, patients must be advised that not taking their prescribed insulin, or taking less insulin than prescribed, is not a safe alternative. An individualized cost-benefit analysis between patient and provider can help to determine the best option for each patient. After working in endocrinology for 5 years, I have learned the following 10 ways to help patients whose financial situations limit their access to insulin.
1 Try older insulins, including mixed insulin 70/30 or 50/50, insulin NPH, or regular insulin. Because the beneficial effects may not be as long lasting with these as with newer insulins on the market, your patient may need to test glucose levels more frequently. Also, insulin NPH and any mixed insulins are suspensions, not solutions, so patients will need to gently roll older insulins prior to use. Those in pen form may also have a shorter shelf life.
2 Switch to a syringe and vial. Although dosing can be less precise, this could be a viable option for patients with good vision and dexterity. This method helps patients save in 3 ways: (1) the insulin is less expensive; (2) syringes generally cost less (about $30 for 100) than pen needle tips (about $50 for 100); and (3) vials of NPH are longer-lasting suspensions that are stable for about 28 days once opened, compared to 14 days for pens.2-4
3 Switch from a 30- to a 90-day supply of refills. This helps to lower copays. For example, a mail-order program (eg, Express Scripts) that ships from a warehouse typically offers lower pricing than a brick-and-mortar pharmacy with greater overhead. Many of these programs provide 2-pharmacist verification for accuracy and free home delivery of medications at a 10% discount, as well as 24-hour pharmacist access.5 The ease of obtaining prescriptions by this method also can help with medication adherence.
4 Patient assistance programs (PAPs) offered by insulin manufacturers can help lower costs for patients who find it difficult to afford their medication. Information on these programs is available on the respective company’s websites, usually in multiple languages (although some are limited to English and Spanish). Patients applying for a PAP must provide a proof of income and adhere to the program’s specific criteria. Renewal is typically required each year.6-8
5 Copay cards are available to many patients with private insurance and may help make insulin more affordable. Patients may be able to receive a $25 monthly supply of insulin for up to 1 year (specific terms vary). Maximum contributions and contributions toward deductibles also vary by program, so patients need to familiarize themselves with what their particular copay card allows. Generally, copay cards are not a sustainable long-term solution; for one thing, they expire, and for another, emphasis should be placed on affordable medications rather than affording expensive medications.
[polldaddy:10400221]
Continue to: 6 External PAPs for patients on Medicare...
6 External PAPs for patients on Medicare can help lower the costs of prescription medications.9 A database of pharmaceutical PAPs is available on the Medicare website.10 Some PAPs may help patients on Medicare pay through the $5,100 coverage gap or “donut hole”—a term referring to a gap in prescription drug coverage once patients have met their prescription limit (all Medicare part D plans have a donut hole).11,12 Patients and providers will need to read the fine print when applying for an external PAP, because some have a monthly or one-time start-up fee for processing the paperwork (and note, there is often paperwork for the relief program in addition to the PAP paperwork through the pharmaceutical company).
7 A Program of All-Inclusive Care for the Elderly (PACE) is available in many states; check medicare.gov to see if your state is eligible. For patients 55 and older on Medicare or Medicaid who do not opt for care at a nursing home facility, PACE may be able to provide care and coverage in the patient’s home or at a PACE facility. Services include primary care, hospital care, laboratory and x-ray services, medical specialty services, and prescription drugs. To be eligible for PACE services, the patient must live in the service area of a PACE organization and have a requirement for a nursing home-level of care (as certified by your state).
8 Shop around for the best deal. Encourage your patients to comparison shop for the best prices rather than accepting the first or only option at their usual pharmacy. Different pharmacies offer drugs at lower prices than competitors. Also, continually compare prices at GoodRx or HealthWarehouse.com. The latter—a fully licensed Internet-based pharmacy—sells FDA-approved medications at affordable prices in all 50 states, without the requirement for insurance coverage.
9 Use of a patch pump may be less expensive for patients with type 2 diabetes who are taking basal-bolus regimens. Patches slowly deliver single short-acting insulin (usually insulin aspart or lispro) that acts as a basal insulin, with an additional reservoir for prandial insulin at mealtime and for snacks. As there is a catheter in the patch, patients would not require the use of needles.13
10 Try removing mealtime insulin for patients with type 2 diabetes who need minimal mealtime insulin. Clinicians can initiate a safe trial of this removal by encouraging the patient to consume a low-carbohydrate diet, increase exercise, and/or use other noninsulin medications that are more affordable.
Continue to: The affordability of insulins...
The affordability of insulins is a potentially uncomfortable but necessary conversation to have with your patient. Providers are one of the best resources for patients who seek relief from financial difficulties. The recommendations discussed here can help providers and patients design a cost-conscious plan for insulin treatment. Although each recommendation is viable, the pros and cons must be weighed on a case-by-case basis. Providers and patients should also pay attention to the Senate Finance Committee’s ongoing discussions and possible resolutions that could result in lower insulin costs. Until legislation that lowers the prices of insulin comes to fruition, however, providers should continue to plan with their patients on how to best get their insulin at the lowest cost.
Test yourself with the poll here.
Almost a century after its discovery, insulin remains a life-saving yet costly medication: In the past 15 years, prices have risen more than 500%.1 Patients may ask you why the insulin you prescribe is so expensive, and the complex process for determining drug costs makes it difficult to answer. But the bottom line is, patients need their insulin—and they want it without breaking the bank.
Thankfully, there are several strategies for reducing the cost of insulin. First and foremost, patients must be advised that not taking their prescribed insulin, or taking less insulin than prescribed, is not a safe alternative. An individualized cost-benefit analysis between patient and provider can help to determine the best option for each patient. After working in endocrinology for 5 years, I have learned the following 10 ways to help patients whose financial situations limit their access to insulin.
1 Try older insulins, including mixed insulin 70/30 or 50/50, insulin NPH, or regular insulin. Because the beneficial effects may not be as long lasting with these as with newer insulins on the market, your patient may need to test glucose levels more frequently. Also, insulin NPH and any mixed insulins are suspensions, not solutions, so patients will need to gently roll older insulins prior to use. Those in pen form may also have a shorter shelf life.
2 Switch to a syringe and vial. Although dosing can be less precise, this could be a viable option for patients with good vision and dexterity. This method helps patients save in 3 ways: (1) the insulin is less expensive; (2) syringes generally cost less (about $30 for 100) than pen needle tips (about $50 for 100); and (3) vials of NPH are longer-lasting suspensions that are stable for about 28 days once opened, compared to 14 days for pens.2-4
3 Switch from a 30- to a 90-day supply of refills. This helps to lower copays. For example, a mail-order program (eg, Express Scripts) that ships from a warehouse typically offers lower pricing than a brick-and-mortar pharmacy with greater overhead. Many of these programs provide 2-pharmacist verification for accuracy and free home delivery of medications at a 10% discount, as well as 24-hour pharmacist access.5 The ease of obtaining prescriptions by this method also can help with medication adherence.
4 Patient assistance programs (PAPs) offered by insulin manufacturers can help lower costs for patients who find it difficult to afford their medication. Information on these programs is available on the respective company’s websites, usually in multiple languages (although some are limited to English and Spanish). Patients applying for a PAP must provide a proof of income and adhere to the program’s specific criteria. Renewal is typically required each year.6-8
5 Copay cards are available to many patients with private insurance and may help make insulin more affordable. Patients may be able to receive a $25 monthly supply of insulin for up to 1 year (specific terms vary). Maximum contributions and contributions toward deductibles also vary by program, so patients need to familiarize themselves with what their particular copay card allows. Generally, copay cards are not a sustainable long-term solution; for one thing, they expire, and for another, emphasis should be placed on affordable medications rather than affording expensive medications.
[polldaddy:10400221]
Continue to: 6 External PAPs for patients on Medicare...
6 External PAPs for patients on Medicare can help lower the costs of prescription medications.9 A database of pharmaceutical PAPs is available on the Medicare website.10 Some PAPs may help patients on Medicare pay through the $5,100 coverage gap or “donut hole”—a term referring to a gap in prescription drug coverage once patients have met their prescription limit (all Medicare part D plans have a donut hole).11,12 Patients and providers will need to read the fine print when applying for an external PAP, because some have a monthly or one-time start-up fee for processing the paperwork (and note, there is often paperwork for the relief program in addition to the PAP paperwork through the pharmaceutical company).
7 A Program of All-Inclusive Care for the Elderly (PACE) is available in many states; check medicare.gov to see if your state is eligible. For patients 55 and older on Medicare or Medicaid who do not opt for care at a nursing home facility, PACE may be able to provide care and coverage in the patient’s home or at a PACE facility. Services include primary care, hospital care, laboratory and x-ray services, medical specialty services, and prescription drugs. To be eligible for PACE services, the patient must live in the service area of a PACE organization and have a requirement for a nursing home-level of care (as certified by your state).
8 Shop around for the best deal. Encourage your patients to comparison shop for the best prices rather than accepting the first or only option at their usual pharmacy. Different pharmacies offer drugs at lower prices than competitors. Also, continually compare prices at GoodRx or HealthWarehouse.com. The latter—a fully licensed Internet-based pharmacy—sells FDA-approved medications at affordable prices in all 50 states, without the requirement for insurance coverage.
9 Use of a patch pump may be less expensive for patients with type 2 diabetes who are taking basal-bolus regimens. Patches slowly deliver single short-acting insulin (usually insulin aspart or lispro) that acts as a basal insulin, with an additional reservoir for prandial insulin at mealtime and for snacks. As there is a catheter in the patch, patients would not require the use of needles.13
10 Try removing mealtime insulin for patients with type 2 diabetes who need minimal mealtime insulin. Clinicians can initiate a safe trial of this removal by encouraging the patient to consume a low-carbohydrate diet, increase exercise, and/or use other noninsulin medications that are more affordable.
Continue to: The affordability of insulins...
The affordability of insulins is a potentially uncomfortable but necessary conversation to have with your patient. Providers are one of the best resources for patients who seek relief from financial difficulties. The recommendations discussed here can help providers and patients design a cost-conscious plan for insulin treatment. Although each recommendation is viable, the pros and cons must be weighed on a case-by-case basis. Providers and patients should also pay attention to the Senate Finance Committee’s ongoing discussions and possible resolutions that could result in lower insulin costs. Until legislation that lowers the prices of insulin comes to fruition, however, providers should continue to plan with their patients on how to best get their insulin at the lowest cost.
Test yourself with the poll here.
1. Grassley, Wyden launch bipartisan investigation into insulin prices. United States Senate Committee on Finance website. www.finance.senate.gov/chairmans-news/grassley-wyden-launch-bipartisan-investigation-into-insulin-prices. Published February 22, 2019. Accessed August 16, 2019.
2. BD Ultra-Fine. Syringe. GoodRx website. www.goodrx.com/bd-ultra-fine?dosage=31-gauge-5-16%22-of-1-cc&form=syringe&label_override=BD+Ultra-Fine&quantity=100. Accessed August 16, 2019.
3. BD Ultra-Fine. Pen needle. GoodRx website. www.goodrx.com/bd-ultra-fine?dosage=5-32%22-of-32-gauge&form=pen-needle&label_override=BD+Ultra-Fine&quantity=100. Accessed August 16, 2019.
4. Joffee D. Stability of common insulins in pens and vials. Diabetes in Control website. www.diabetesincontrol.com/wp-content/uploads/PDF/se_insulin_stability_chart.pdf. Published September 2011. Accessed August 16, 2019.
5. Frequently asked questions. Preferred home delivery program for maintenance medications. Express Scripts website. www.express-scripts.com/art/pdf/SST-custom-preferred-faq.pdf. Accessed August 16, 2019.
6. Patient Connection. Sanofi Patient Connection website. www.sanofipatientconnection.com/. Accessed August 16, 2019.
7. The Lilly Cares Foundation Patient Assistance Program. Lilly website. www.lillycares.com/assistanceprograms.aspx. Accessed August 16, 2019.
8. Novo Nordisk Patient Assistance Program. NovoCare website. www.novocare.com/psp/PAP.html. Accessed August 16, 2019.
9. 6 ways to get help with prescription costs. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/costs-in-the-coverage-gap/6-ways-to-get-help-with-prescription-costs. Accessed August 16, 2019.
10. Pharmaceutical assistance program. Medicare website. www.medicare.gov/pharmaceutical-assistance-program/Index.aspx. Accessed August 16, 2019.
11. Catastrophic coverage. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/catastrophic-coverage. Accessed August 16, 2019.
12. Costs in the coverage gap. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/costs-in-the-coverage-gap. Accessed August 16, 2019.
13. V-Go Reimbursement Assistance Program. V-Go website. www.go-vgo.com/coverage-savings/overview/. Accessed August 16, 2019.
1. Grassley, Wyden launch bipartisan investigation into insulin prices. United States Senate Committee on Finance website. www.finance.senate.gov/chairmans-news/grassley-wyden-launch-bipartisan-investigation-into-insulin-prices. Published February 22, 2019. Accessed August 16, 2019.
2. BD Ultra-Fine. Syringe. GoodRx website. www.goodrx.com/bd-ultra-fine?dosage=31-gauge-5-16%22-of-1-cc&form=syringe&label_override=BD+Ultra-Fine&quantity=100. Accessed August 16, 2019.
3. BD Ultra-Fine. Pen needle. GoodRx website. www.goodrx.com/bd-ultra-fine?dosage=5-32%22-of-32-gauge&form=pen-needle&label_override=BD+Ultra-Fine&quantity=100. Accessed August 16, 2019.
4. Joffee D. Stability of common insulins in pens and vials. Diabetes in Control website. www.diabetesincontrol.com/wp-content/uploads/PDF/se_insulin_stability_chart.pdf. Published September 2011. Accessed August 16, 2019.
5. Frequently asked questions. Preferred home delivery program for maintenance medications. Express Scripts website. www.express-scripts.com/art/pdf/SST-custom-preferred-faq.pdf. Accessed August 16, 2019.
6. Patient Connection. Sanofi Patient Connection website. www.sanofipatientconnection.com/. Accessed August 16, 2019.
7. The Lilly Cares Foundation Patient Assistance Program. Lilly website. www.lillycares.com/assistanceprograms.aspx. Accessed August 16, 2019.
8. Novo Nordisk Patient Assistance Program. NovoCare website. www.novocare.com/psp/PAP.html. Accessed August 16, 2019.
9. 6 ways to get help with prescription costs. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/costs-in-the-coverage-gap/6-ways-to-get-help-with-prescription-costs. Accessed August 16, 2019.
10. Pharmaceutical assistance program. Medicare website. www.medicare.gov/pharmaceutical-assistance-program/Index.aspx. Accessed August 16, 2019.
11. Catastrophic coverage. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/catastrophic-coverage. Accessed August 16, 2019.
12. Costs in the coverage gap. Medicare website. www.medicare.gov/drug-coverage-part-d/costs-for-medicare-drug-coverage/costs-in-the-coverage-gap. Accessed August 16, 2019.
13. V-Go Reimbursement Assistance Program. V-Go website. www.go-vgo.com/coverage-savings/overview/. Accessed August 16, 2019.
Clinical outcomes in diabetes: It’s not just the glucose (and it’s not so simple)
There has been increasing emphasis from drug regulatory agencies on collecting robust data on multiple outcomes from clinical trials in addition to the efficacy outcomes and usual safety data. For about a decade, the US Food and Drug Administration has required the collection of cardiovascular outcome data during the testing of new antidiabetic therapies. There are several potential consequences of this mandate, in addition to our now having a better understanding of cardiovascular risk. Studies are likely to be larger, longer, and more expensive. Patient cohorts are selected with this in mind, meaning that studies may be harder to compare, and labeled indications may be more specific. And we now have several drugs carrying a specific indication to reduce cardiovascular death in patients with diabetes!
But as we dig deeper into the reduction in cardiovascular deaths seen in clinical trials with some of the sodium-glucose cotransporter 2 (SGLT2) inhibitors, several questions arise. Why is their effect on mortality and cardiovascular events (and preservation of renal function) not a consistent drug class effect? All of these inhibitors decrease glucose reabsorption and thus cause glucosuria, resulting in lower blood glucose levels with modest caloric wasting and weight loss, as well as natriuresis with mild volume depletion. But the individual drugs behaved slightly differently in clinical trials. Perhaps this was due to slightly different trial populations, or chance (despite large trial numbers), or maybe molecular differences in the drugs despite their shared effect on glucosuria, resulting in distinct “off-target” effects. Perhaps the drugs differentially affect other transporters, on cells other than renal tubular cells, altering their function. An additional known effect of the drug class is uricosuria and mild relative hypouricemia. The differential effects of these drugs on urate transport into and out of different cells that may influence components of the metabolic syndrome and cardiovascular and renal outcomes has yet to be fully explored.
But one thing that seems to be true is that the effect of empagliflozin and canagliflozin on cardiac mortality is not due to simply lowering the blood glucose. Trials like the UK Prospective Diabetes Study1 demonstrated that better glucose control reduced microvascular complications, but they did not initially show a reduction in myocardial infarction. It took long-term follow-up studies to indicate that more intensive initial glucose control could reduce cardiovascular events. But a beneficial effect of empagliflozin (compared with placebo) on cardiovascular mortality (but interestingly not on stroke or nonfatal myocardial infarction) was seen within 3 months.2 This observation suggests unique properties of this drug and some others in the class, in addition to their glucose-lowering effect. Puzzling to me, looking at several of the SGLT2 inhibitor drug studies, is why they seemed to behave differently in terms of different cardiovascular outcomes (eg, heart failure, stroke, nonfatal myocardial infarction, need for limb amputation). While some of these seemingly paradoxical outcomes have also been seen in studies of other drugs, these differences are hard for me to understand on a biological basis: they do not seem consistent with simply differential drug effects on either acute thrombosis or chronic hypoperfusion. We have much more to learn.
For the moment, I suppose we should let our practice be guided by the results of specific clinical trials, hoping that at some point head-to-head comparator drug trials will be undertaken to provide us with even better guidance in drug selection.
We can also hope that our patients with diabetes will somehow be able to afford our increasingly complex and evidence-supported pharmacotherapy, as now not only can we lower the levels of blood glucose and biomarkers of comorbidity, we can also reduce adverse cardiovascular outcomes.
- Holman RR, Paul SK, Bethel MA, Matthews DR, Neil AW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359(15):1577–1589. doi:10.1056/NEJMoa0806470
- Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OuTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22):2117–2128. doi:10.1056/NEJMoa1504720
There has been increasing emphasis from drug regulatory agencies on collecting robust data on multiple outcomes from clinical trials in addition to the efficacy outcomes and usual safety data. For about a decade, the US Food and Drug Administration has required the collection of cardiovascular outcome data during the testing of new antidiabetic therapies. There are several potential consequences of this mandate, in addition to our now having a better understanding of cardiovascular risk. Studies are likely to be larger, longer, and more expensive. Patient cohorts are selected with this in mind, meaning that studies may be harder to compare, and labeled indications may be more specific. And we now have several drugs carrying a specific indication to reduce cardiovascular death in patients with diabetes!
But as we dig deeper into the reduction in cardiovascular deaths seen in clinical trials with some of the sodium-glucose cotransporter 2 (SGLT2) inhibitors, several questions arise. Why is their effect on mortality and cardiovascular events (and preservation of renal function) not a consistent drug class effect? All of these inhibitors decrease glucose reabsorption and thus cause glucosuria, resulting in lower blood glucose levels with modest caloric wasting and weight loss, as well as natriuresis with mild volume depletion. But the individual drugs behaved slightly differently in clinical trials. Perhaps this was due to slightly different trial populations, or chance (despite large trial numbers), or maybe molecular differences in the drugs despite their shared effect on glucosuria, resulting in distinct “off-target” effects. Perhaps the drugs differentially affect other transporters, on cells other than renal tubular cells, altering their function. An additional known effect of the drug class is uricosuria and mild relative hypouricemia. The differential effects of these drugs on urate transport into and out of different cells that may influence components of the metabolic syndrome and cardiovascular and renal outcomes has yet to be fully explored.
But one thing that seems to be true is that the effect of empagliflozin and canagliflozin on cardiac mortality is not due to simply lowering the blood glucose. Trials like the UK Prospective Diabetes Study1 demonstrated that better glucose control reduced microvascular complications, but they did not initially show a reduction in myocardial infarction. It took long-term follow-up studies to indicate that more intensive initial glucose control could reduce cardiovascular events. But a beneficial effect of empagliflozin (compared with placebo) on cardiovascular mortality (but interestingly not on stroke or nonfatal myocardial infarction) was seen within 3 months.2 This observation suggests unique properties of this drug and some others in the class, in addition to their glucose-lowering effect. Puzzling to me, looking at several of the SGLT2 inhibitor drug studies, is why they seemed to behave differently in terms of different cardiovascular outcomes (eg, heart failure, stroke, nonfatal myocardial infarction, need for limb amputation). While some of these seemingly paradoxical outcomes have also been seen in studies of other drugs, these differences are hard for me to understand on a biological basis: they do not seem consistent with simply differential drug effects on either acute thrombosis or chronic hypoperfusion. We have much more to learn.
For the moment, I suppose we should let our practice be guided by the results of specific clinical trials, hoping that at some point head-to-head comparator drug trials will be undertaken to provide us with even better guidance in drug selection.
We can also hope that our patients with diabetes will somehow be able to afford our increasingly complex and evidence-supported pharmacotherapy, as now not only can we lower the levels of blood glucose and biomarkers of comorbidity, we can also reduce adverse cardiovascular outcomes.
There has been increasing emphasis from drug regulatory agencies on collecting robust data on multiple outcomes from clinical trials in addition to the efficacy outcomes and usual safety data. For about a decade, the US Food and Drug Administration has required the collection of cardiovascular outcome data during the testing of new antidiabetic therapies. There are several potential consequences of this mandate, in addition to our now having a better understanding of cardiovascular risk. Studies are likely to be larger, longer, and more expensive. Patient cohorts are selected with this in mind, meaning that studies may be harder to compare, and labeled indications may be more specific. And we now have several drugs carrying a specific indication to reduce cardiovascular death in patients with diabetes!
But as we dig deeper into the reduction in cardiovascular deaths seen in clinical trials with some of the sodium-glucose cotransporter 2 (SGLT2) inhibitors, several questions arise. Why is their effect on mortality and cardiovascular events (and preservation of renal function) not a consistent drug class effect? All of these inhibitors decrease glucose reabsorption and thus cause glucosuria, resulting in lower blood glucose levels with modest caloric wasting and weight loss, as well as natriuresis with mild volume depletion. But the individual drugs behaved slightly differently in clinical trials. Perhaps this was due to slightly different trial populations, or chance (despite large trial numbers), or maybe molecular differences in the drugs despite their shared effect on glucosuria, resulting in distinct “off-target” effects. Perhaps the drugs differentially affect other transporters, on cells other than renal tubular cells, altering their function. An additional known effect of the drug class is uricosuria and mild relative hypouricemia. The differential effects of these drugs on urate transport into and out of different cells that may influence components of the metabolic syndrome and cardiovascular and renal outcomes has yet to be fully explored.
But one thing that seems to be true is that the effect of empagliflozin and canagliflozin on cardiac mortality is not due to simply lowering the blood glucose. Trials like the UK Prospective Diabetes Study1 demonstrated that better glucose control reduced microvascular complications, but they did not initially show a reduction in myocardial infarction. It took long-term follow-up studies to indicate that more intensive initial glucose control could reduce cardiovascular events. But a beneficial effect of empagliflozin (compared with placebo) on cardiovascular mortality (but interestingly not on stroke or nonfatal myocardial infarction) was seen within 3 months.2 This observation suggests unique properties of this drug and some others in the class, in addition to their glucose-lowering effect. Puzzling to me, looking at several of the SGLT2 inhibitor drug studies, is why they seemed to behave differently in terms of different cardiovascular outcomes (eg, heart failure, stroke, nonfatal myocardial infarction, need for limb amputation). While some of these seemingly paradoxical outcomes have also been seen in studies of other drugs, these differences are hard for me to understand on a biological basis: they do not seem consistent with simply differential drug effects on either acute thrombosis or chronic hypoperfusion. We have much more to learn.
For the moment, I suppose we should let our practice be guided by the results of specific clinical trials, hoping that at some point head-to-head comparator drug trials will be undertaken to provide us with even better guidance in drug selection.
We can also hope that our patients with diabetes will somehow be able to afford our increasingly complex and evidence-supported pharmacotherapy, as now not only can we lower the levels of blood glucose and biomarkers of comorbidity, we can also reduce adverse cardiovascular outcomes.
- Holman RR, Paul SK, Bethel MA, Matthews DR, Neil AW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359(15):1577–1589. doi:10.1056/NEJMoa0806470
- Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OuTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22):2117–2128. doi:10.1056/NEJMoa1504720
- Holman RR, Paul SK, Bethel MA, Matthews DR, Neil AW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008; 359(15):1577–1589. doi:10.1056/NEJMoa0806470
- Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OuTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015; 373(22):2117–2128. doi:10.1056/NEJMoa1504720
Diabetic dyslipidemia with eruptive xanthoma
A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.
Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.
A RESULT OF ELEVATED TRIGLYCERIDES
Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.1 Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.
Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.2,3
Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.4
Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),5 with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).6 Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.
RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS
Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.
Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,7 and drug therapy.
The patient’s treatment plan
Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.8 Omega-3 fatty acids, statins, or niacin may be added if necessary.8
Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.
- Flynn PD, Burns T, Breathnach S, Cox N, Griffiths C. Xanthomas and abnormalities of lipid metabolism and storage. In: Rook’s Textbook of Dermatology. 8th ed. Oxford: Blackwell Science; 2010.
- Breckenridge WC, Alaupovic P, Cox DW, Little JA. Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. Atherosclerosis 1982; 44(2):223–235. pmid:7138621
- Santamarina-Fojo S. The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am 1998; 27(3):551–567. pmid:9785052
- Melmed S, Polonsky KS, Larsen PR, Kronenberg H. Williams Textbook of Endocrinology. 13th ed. Philadelphia: Elsevier; 2016.
- Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158(2):181–188. doi:10.5507/bp.2014.016
- Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med 2008; 121(1):10–12. doi:10.1016/j.amjmed.2007.10.004
- Hegele RA, Ginsberg HN, Chapman MJ, et al; European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2014; 2(8):655–666. doi:10.1016/S2213-8587(13)70191-8
- Berglund L, Brunzell JD, Goldberg AC, et al; Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97(9):2969–2989. doi:10.1210/jc.2011-3213
A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.
Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.
A RESULT OF ELEVATED TRIGLYCERIDES
Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.1 Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.
Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.2,3
Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.4
Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),5 with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).6 Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.
RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS
Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.
Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,7 and drug therapy.
The patient’s treatment plan
Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.8 Omega-3 fatty acids, statins, or niacin may be added if necessary.8
Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.
A workup for secondary causes of hypertriglyceridemia was negative for hypothyroidism and nephrotic syndrome. She was currently taking no medications. She had no family history of dyslipidemia, and she denied alcohol consumption.
Based on the patient’s presentation, history, and the results of laboratory testing and skin biopsy, the diagnosis was eruptive xanthoma.
A RESULT OF ELEVATED TRIGLYCERIDES
Eruptive xanthoma is associated with elevation of chylomicrons and triglycerides.1 Hyperlipidemia that causes eruptive xanthoma may be familial (ie, due to a primary genetic defect) or secondary to another disease, or both.
Types of primary hypertriglyceridemia include elevated chylomicrons (Frederickson classification type I), elevated very-low-density lipoprotein (VLDL) (Frederickson type IV), and elevation of both chylomicrons and VLDL (Frederickson type V).2,3 Hypertriglyceridemia may also be secondary to obesity, diabetes mellitus, hypothyroidism, nephrotic syndrome, liver cirrhosis, excess ethanol ingestion, and medicines such as retinoids and estrogens.2,3
Lesions of eruptive xanthoma are yellowish papules 2 to 5 mm in diameter surrounded by an erythematous border. They are formed by clusters of foamy cells caused by phagocytosis of macrophages as a consequence of increased accumulations of intracellular lipids. The most common sites are the buttocks, extensor surfaces of the arms, and the back.4
Eruptive xanthoma occurs with markedly elevated triglyceride levels (ie, > 1,000 mg/dL),5 with an estimated prevalence of 18 cases per 100,000 people (< 0.02%).6 Diagnosis is usually established through the clinical history, physical examination, and prompt laboratory confirmation of hypertriglyceridemia. Skin biopsy is rarely if ever needed.
RECOGNIZE AND TREAT PROMPTLY TO AVOID FURTHER COMPLICATIONS
Severe hypertriglyceridemia poses an increased risk of acute pancreatitis. Early recognition and medical treatment in our patient prevented serious complications.
Treatment of eruptive xanthoma includes identifying the underlying cause of hypertriglyceridemia and commencing lifestyle modifications that include weight reduction, aerobic exercise, a strict low-fat diet with avoidance of simple carbohydrates and alcohol,7 and drug therapy.
The patient’s treatment plan
Although HMG-CoA reductase inhibitors (statins) have a modest triglyceride-lowering effect and are useful to modify cardiovascular risk, fibric acid derivatives (eg, gemfibrozil, fenofibrate) are the first-line therapy.8 Omega-3 fatty acids, statins, or niacin may be added if necessary.8
Our patient’s uncontrolled glycemia caused marked hypertriglyceridemia, perhaps from a decrease in lipoprotein lipase activity in adipose tissue and muscle. Lifestyle modifications, glucose-lowering agents (metformin, glimepiride), and fenofibrate were prescribed. She was also advised to seek medical attention if she developed upper-abdominal pain, which could be a symptom of pancreatitis.
- Flynn PD, Burns T, Breathnach S, Cox N, Griffiths C. Xanthomas and abnormalities of lipid metabolism and storage. In: Rook’s Textbook of Dermatology. 8th ed. Oxford: Blackwell Science; 2010.
- Breckenridge WC, Alaupovic P, Cox DW, Little JA. Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. Atherosclerosis 1982; 44(2):223–235. pmid:7138621
- Santamarina-Fojo S. The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am 1998; 27(3):551–567. pmid:9785052
- Melmed S, Polonsky KS, Larsen PR, Kronenberg H. Williams Textbook of Endocrinology. 13th ed. Philadelphia: Elsevier; 2016.
- Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158(2):181–188. doi:10.5507/bp.2014.016
- Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med 2008; 121(1):10–12. doi:10.1016/j.amjmed.2007.10.004
- Hegele RA, Ginsberg HN, Chapman MJ, et al; European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2014; 2(8):655–666. doi:10.1016/S2213-8587(13)70191-8
- Berglund L, Brunzell JD, Goldberg AC, et al; Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97(9):2969–2989. doi:10.1210/jc.2011-3213
- Flynn PD, Burns T, Breathnach S, Cox N, Griffiths C. Xanthomas and abnormalities of lipid metabolism and storage. In: Rook’s Textbook of Dermatology. 8th ed. Oxford: Blackwell Science; 2010.
- Breckenridge WC, Alaupovic P, Cox DW, Little JA. Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency. Atherosclerosis 1982; 44(2):223–235. pmid:7138621
- Santamarina-Fojo S. The familial chylomicronemia syndrome. Endocrinol Metab Clin North Am 1998; 27(3):551–567. pmid:9785052
- Melmed S, Polonsky KS, Larsen PR, Kronenberg H. Williams Textbook of Endocrinology. 13th ed. Philadelphia: Elsevier; 2016.
- Zak A, Zeman M, Slaby A, Vecka M. Xanthomas: clinical and pathophysiological relations. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2014; 158(2):181–188. doi:10.5507/bp.2014.016
- Leaf DA. Chylomicronemia and the chylomicronemia syndrome: a practical approach to management. Am J Med 2008; 121(1):10–12. doi:10.1016/j.amjmed.2007.10.004
- Hegele RA, Ginsberg HN, Chapman MJ, et al; European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2014; 2(8):655–666. doi:10.1016/S2213-8587(13)70191-8
- Berglund L, Brunzell JD, Goldberg AC, et al; Endocrine Society. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2012; 97(9):2969–2989. doi:10.1210/jc.2011-3213
