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Diabetes treatment costs doubled in Sweden since 2006
MUNICH – Sweden has experienced a doubling in its national costs for treating type 2 diabetes from €608 million in 2006 to €1.27 billion in 2014.
The increase is directly related to a surge of more than 100,000 in the number of patients with the disease and has been driven by increased hospitalizations for cardiovascular complications of diabetes, Almina Kalkan, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.
Costs jumped on a per-patient level as well, but the increase wasn’t related to diabetes treatment – in fact, antidiabetic medication costs remained stable at 4% over the entire study period. The real driver was the cost of treating heart failure and stroke, which increased by 92% and 73%, respectively, over the study period.
“You can really see that preventing these diabetes complications is of major importance, not only for patient quality of life but for reducing health care expenditures,” said Dr. Kalkan.
She and her colleagues searched the Swedish Prescribed Drug Registry to identify patients treated for type 2 diabetes, and linked those patients with annual hospital admissions, discharges, and hospital outpatient visits in the National Patient Register. This database doesn’t contain information on primary care visits, so this was imputed from prior studies, as were data on lost work productivity due to the disease.
According to national records, 206,183 Swedish citizens were treated for type 2 diabetes in 2006; by 2014, that number was 366,492. The mean patient age was unchanged (67 years). There was a significant increase of 2% in the number of patients who had cardiovascular disease (33%-35%). That was driven by increases in heart failure and atrial fibrillation; the proportion with myocardial infarction and stroke was unchanged.
Significantly more patients also had kidney disease by 2014 (1.5%-3.2%), although macrovascular disease had decreased by 4%. Lower limb amputations increased as well.
In the overall analysis, inpatient hospital visits accounted for the bulk of the spending, rising from €355 million in 2006 to €783 million in 2014. This was followed by spending on outpatient hospital care (from €112 million to €303 million). Spending on diabetes medications went from €39 million to €84 million, but the increase stayed proportional at just over 6%.
The total annual cost per patient increased as well, from just under €3,000/year to €3,500/year – an 18% increase.
“We still see that the main driver was inpatient and outpatient hospital care,“ Dr. Kalkan said. “Total inpatient costs increased by 24% per patient, and total outpatient costs increased by 52%.”
The proportion spent on inpatient and outpatient hospital care for each patient increased from 77% to 85% of total expenditures. Again, there was no change in the cost of diabetes medications or in the proportion of costs spent on such drugs.
Dr. Kalkan and her colleagues then conducted a societal cost analysis, which included data on primary care visits and lost job productivity related to diabetes. There was an overall 22% increase in national cost during the study period, rising from €4,200 to €5,300/patient-year.
“Inpatient visits increased by 72%, although length of stay decreased, from 13 to 11 days,” Dr. Kalkan said. “Despite this, the costs proportionately increased. This was directly due to the cost of treating the most common cardiovascular comorbidities of diabetes: heart failure, chest pain, myocardial infarction, and stroke.”
In this analysis, the cost of antidiabetic drugs was also quite small and remained stable, at 4% over the entire study period.
The cost of lost productivity was drawn from a 2015 report issued by the Swedish Institute for Health Economics. This report found that type 2 diabetes was related to a net per patient loss of €206/year in 2006 and €317/year in 2014 – a significant change.
The cost analysis was a collaborative project of AstraZeneca, Uppsala University, and the Karolinksa Institute. Dr. Kalkan is an employee of AstraZeneca.
[email protected]
On Twitter @Alz_Gal
MUNICH – Sweden has experienced a doubling in its national costs for treating type 2 diabetes from €608 million in 2006 to €1.27 billion in 2014.
The increase is directly related to a surge of more than 100,000 in the number of patients with the disease and has been driven by increased hospitalizations for cardiovascular complications of diabetes, Almina Kalkan, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.
Costs jumped on a per-patient level as well, but the increase wasn’t related to diabetes treatment – in fact, antidiabetic medication costs remained stable at 4% over the entire study period. The real driver was the cost of treating heart failure and stroke, which increased by 92% and 73%, respectively, over the study period.
“You can really see that preventing these diabetes complications is of major importance, not only for patient quality of life but for reducing health care expenditures,” said Dr. Kalkan.
She and her colleagues searched the Swedish Prescribed Drug Registry to identify patients treated for type 2 diabetes, and linked those patients with annual hospital admissions, discharges, and hospital outpatient visits in the National Patient Register. This database doesn’t contain information on primary care visits, so this was imputed from prior studies, as were data on lost work productivity due to the disease.
According to national records, 206,183 Swedish citizens were treated for type 2 diabetes in 2006; by 2014, that number was 366,492. The mean patient age was unchanged (67 years). There was a significant increase of 2% in the number of patients who had cardiovascular disease (33%-35%). That was driven by increases in heart failure and atrial fibrillation; the proportion with myocardial infarction and stroke was unchanged.
Significantly more patients also had kidney disease by 2014 (1.5%-3.2%), although macrovascular disease had decreased by 4%. Lower limb amputations increased as well.
In the overall analysis, inpatient hospital visits accounted for the bulk of the spending, rising from €355 million in 2006 to €783 million in 2014. This was followed by spending on outpatient hospital care (from €112 million to €303 million). Spending on diabetes medications went from €39 million to €84 million, but the increase stayed proportional at just over 6%.
The total annual cost per patient increased as well, from just under €3,000/year to €3,500/year – an 18% increase.
“We still see that the main driver was inpatient and outpatient hospital care,“ Dr. Kalkan said. “Total inpatient costs increased by 24% per patient, and total outpatient costs increased by 52%.”
The proportion spent on inpatient and outpatient hospital care for each patient increased from 77% to 85% of total expenditures. Again, there was no change in the cost of diabetes medications or in the proportion of costs spent on such drugs.
Dr. Kalkan and her colleagues then conducted a societal cost analysis, which included data on primary care visits and lost job productivity related to diabetes. There was an overall 22% increase in national cost during the study period, rising from €4,200 to €5,300/patient-year.
“Inpatient visits increased by 72%, although length of stay decreased, from 13 to 11 days,” Dr. Kalkan said. “Despite this, the costs proportionately increased. This was directly due to the cost of treating the most common cardiovascular comorbidities of diabetes: heart failure, chest pain, myocardial infarction, and stroke.”
In this analysis, the cost of antidiabetic drugs was also quite small and remained stable, at 4% over the entire study period.
The cost of lost productivity was drawn from a 2015 report issued by the Swedish Institute for Health Economics. This report found that type 2 diabetes was related to a net per patient loss of €206/year in 2006 and €317/year in 2014 – a significant change.
The cost analysis was a collaborative project of AstraZeneca, Uppsala University, and the Karolinksa Institute. Dr. Kalkan is an employee of AstraZeneca.
[email protected]
On Twitter @Alz_Gal
MUNICH – Sweden has experienced a doubling in its national costs for treating type 2 diabetes from €608 million in 2006 to €1.27 billion in 2014.
The increase is directly related to a surge of more than 100,000 in the number of patients with the disease and has been driven by increased hospitalizations for cardiovascular complications of diabetes, Almina Kalkan, PhD, reported at the annual meeting of the European Association for the Study of Diabetes.
Costs jumped on a per-patient level as well, but the increase wasn’t related to diabetes treatment – in fact, antidiabetic medication costs remained stable at 4% over the entire study period. The real driver was the cost of treating heart failure and stroke, which increased by 92% and 73%, respectively, over the study period.
“You can really see that preventing these diabetes complications is of major importance, not only for patient quality of life but for reducing health care expenditures,” said Dr. Kalkan.
She and her colleagues searched the Swedish Prescribed Drug Registry to identify patients treated for type 2 diabetes, and linked those patients with annual hospital admissions, discharges, and hospital outpatient visits in the National Patient Register. This database doesn’t contain information on primary care visits, so this was imputed from prior studies, as were data on lost work productivity due to the disease.
According to national records, 206,183 Swedish citizens were treated for type 2 diabetes in 2006; by 2014, that number was 366,492. The mean patient age was unchanged (67 years). There was a significant increase of 2% in the number of patients who had cardiovascular disease (33%-35%). That was driven by increases in heart failure and atrial fibrillation; the proportion with myocardial infarction and stroke was unchanged.
Significantly more patients also had kidney disease by 2014 (1.5%-3.2%), although macrovascular disease had decreased by 4%. Lower limb amputations increased as well.
In the overall analysis, inpatient hospital visits accounted for the bulk of the spending, rising from €355 million in 2006 to €783 million in 2014. This was followed by spending on outpatient hospital care (from €112 million to €303 million). Spending on diabetes medications went from €39 million to €84 million, but the increase stayed proportional at just over 6%.
The total annual cost per patient increased as well, from just under €3,000/year to €3,500/year – an 18% increase.
“We still see that the main driver was inpatient and outpatient hospital care,“ Dr. Kalkan said. “Total inpatient costs increased by 24% per patient, and total outpatient costs increased by 52%.”
The proportion spent on inpatient and outpatient hospital care for each patient increased from 77% to 85% of total expenditures. Again, there was no change in the cost of diabetes medications or in the proportion of costs spent on such drugs.
Dr. Kalkan and her colleagues then conducted a societal cost analysis, which included data on primary care visits and lost job productivity related to diabetes. There was an overall 22% increase in national cost during the study period, rising from €4,200 to €5,300/patient-year.
“Inpatient visits increased by 72%, although length of stay decreased, from 13 to 11 days,” Dr. Kalkan said. “Despite this, the costs proportionately increased. This was directly due to the cost of treating the most common cardiovascular comorbidities of diabetes: heart failure, chest pain, myocardial infarction, and stroke.”
In this analysis, the cost of antidiabetic drugs was also quite small and remained stable, at 4% over the entire study period.
The cost of lost productivity was drawn from a 2015 report issued by the Swedish Institute for Health Economics. This report found that type 2 diabetes was related to a net per patient loss of €206/year in 2006 and €317/year in 2014 – a significant change.
The cost analysis was a collaborative project of AstraZeneca, Uppsala University, and the Karolinksa Institute. Dr. Kalkan is an employee of AstraZeneca.
[email protected]
On Twitter @Alz_Gal
AT EASD 2016
Key clinical point:
Major finding: Treatment costs jumped from €608 million in 2006 to €1.27 billion in 2014.
Data source: The 8-year study used national health care data.
Disclosures: The cost analysis was a collaborative project of AstraZeneca, Uppsala University, and the Karolinksa Institute. Dr. Kalkan is an employee of AstraZeneca.
‘Bionic pancreas’ employs glucagon and insulin to stabilize blood sugar
MUNICH – A “bionic pancreas” that delivers glucagon as well as insulin fared well against conventional insulin pump therapy, significantly reducing mean glucose levels and minimizing time spent in hypoglycemia.
The iLet bionic pancreas is being developed by Beta Bionics in conjunction with Eli Lilly and with support from the National Institutes of Health. Beta Bionics bills itself as a public benefit corporation – “a for-profit entity also dedicated to social responsibility and a public benefit mission,” according to an article published by Boston University.
Glucagon is the key that takes the bionic pancreas above and beyond what current insulin pump systems can do, said Dr. Russell, an endocrinologist at Massachusetts General Hospital, Boston.
“Even the pancreas, which has all the advantages of releasing insulin right into the portal vein and directly sensing glucose in the blood, uses the countering hormone, glucagon, to prevent hypoglycemia, particularly during exercise and in the late postprandial phase,” he said. “We are trying to mimic that capability. Glucagon gives us an additional tool to further reduce the risk of hypoglycemia.”
The algorithm is almost completely independent of user input – another key benefit, Dr. Russell said. It initializes with input about the patient’s weight and adapts its insulin delivery by essentially learning each user. There is no need to count carbohydrates, for example. The system “learns” over time its user’s typical meal patterns and can be programmed to deliver insulin accordingly.
“The user can enter, for example, ‘typical lunch,’ and the system will dispense some insulin before the meal and the rest later, in automatic delivery mode.”
The iLet has been studied in several settings and populations including, most recently, a successful crossover trial in 19 children at a diabetes camp (Lancet Diabetes Endocrinol. 2016; 4[3]:233-43).
The device was similarly successful in both teens and adults.
The study Dr. Russell reported at EASD 2016 comprised 39 patients with type 1 diabetes who were using an insulin pump. The mean age of the patients was 33 years, and mean disease duration was 17 years. The mean daily insulin dose was 0.6 U/kg. The mean baseline hemoglobin A1c was 7.7% and mean blood glucose, 176 mg/dL.
The crossover trial randomized patients to 11 days of treatment with their existing Medtronic insulin pump or the iLet system. The primary outcomes were the mean glucose level and time spent in hypoglycemic range (less than 60 mg/dL).
Under the usual care arm, “We saw a wide range of glucose values, which became much tighter when patients were using the bionic pancreas,” Dr. Russell said.
The overall average glucose level was 9 mmol/L in the usual care arm vs. 7.8 mmol/L in the bionic pancreas arm. Time in hypoglycemia was significantly reduced (27 minutes/24 hours vs. 9 minutes/24 hours).
“The standard deviation of the mean glucose was also larger in usual care, which is consistent with the automatic adaptive function of the bionic pancreas. If the mean glucose gets too high, it treats more aggressively; and if glucose is too low, it becomes less aggressive.”
The average amount of insulin used per day was similar (0.62 U/kg vs. 0.66 U/kg) and the average amount of glucagon used was 0.5 mg/day in each group.
During the night, the bionic pancreas kept mean blood glucose lower (134 mg/dL vs. 165 mg/dL) and more stable, reducing time in hypoglycemia (1.4 minutes/night vs. 4.8 minutes/night).
There was one incident of severe hypoglycemia in the usual-care arm, and none in the bionic-pancreas arm. There was a statistically significant increase in nausea associated with the glucagon, Dr. Russell noted, but the impact was still quite small. On a 0-10 rating scale, nausea in the bionic pancreas group was rated a 0.5 compared to a 0.05 in the usual care arm.
There were no changes in blood pressure, weight, or any lab test.
The ongoing studies continue to show “that automated bihormonal control of glycemia in the home-use setting is feasible,” Dr. Russell said. “Micro-dose glucagon was well tolerated and the bihormonal pancreas reduced both mean glucose and hypoglycemia relative to the patients’ usual care devices.”
The iLet continues to undergo modifications that are making it more user friendly, he added.
Dr. Stevens disclosed that he has a patent pending on “certain aspects” of the device, and that he is an unpaid scientific consultant for Beta Bionics. He also disclosed financial relationships with several pharmaceutical and device companies, including Eli Lilly and Medtronic.
MUNICH – A “bionic pancreas” that delivers glucagon as well as insulin fared well against conventional insulin pump therapy, significantly reducing mean glucose levels and minimizing time spent in hypoglycemia.
The iLet bionic pancreas is being developed by Beta Bionics in conjunction with Eli Lilly and with support from the National Institutes of Health. Beta Bionics bills itself as a public benefit corporation – “a for-profit entity also dedicated to social responsibility and a public benefit mission,” according to an article published by Boston University.
Glucagon is the key that takes the bionic pancreas above and beyond what current insulin pump systems can do, said Dr. Russell, an endocrinologist at Massachusetts General Hospital, Boston.
“Even the pancreas, which has all the advantages of releasing insulin right into the portal vein and directly sensing glucose in the blood, uses the countering hormone, glucagon, to prevent hypoglycemia, particularly during exercise and in the late postprandial phase,” he said. “We are trying to mimic that capability. Glucagon gives us an additional tool to further reduce the risk of hypoglycemia.”
The algorithm is almost completely independent of user input – another key benefit, Dr. Russell said. It initializes with input about the patient’s weight and adapts its insulin delivery by essentially learning each user. There is no need to count carbohydrates, for example. The system “learns” over time its user’s typical meal patterns and can be programmed to deliver insulin accordingly.
“The user can enter, for example, ‘typical lunch,’ and the system will dispense some insulin before the meal and the rest later, in automatic delivery mode.”
The iLet has been studied in several settings and populations including, most recently, a successful crossover trial in 19 children at a diabetes camp (Lancet Diabetes Endocrinol. 2016; 4[3]:233-43).
The device was similarly successful in both teens and adults.
The study Dr. Russell reported at EASD 2016 comprised 39 patients with type 1 diabetes who were using an insulin pump. The mean age of the patients was 33 years, and mean disease duration was 17 years. The mean daily insulin dose was 0.6 U/kg. The mean baseline hemoglobin A1c was 7.7% and mean blood glucose, 176 mg/dL.
The crossover trial randomized patients to 11 days of treatment with their existing Medtronic insulin pump or the iLet system. The primary outcomes were the mean glucose level and time spent in hypoglycemic range (less than 60 mg/dL).
Under the usual care arm, “We saw a wide range of glucose values, which became much tighter when patients were using the bionic pancreas,” Dr. Russell said.
The overall average glucose level was 9 mmol/L in the usual care arm vs. 7.8 mmol/L in the bionic pancreas arm. Time in hypoglycemia was significantly reduced (27 minutes/24 hours vs. 9 minutes/24 hours).
“The standard deviation of the mean glucose was also larger in usual care, which is consistent with the automatic adaptive function of the bionic pancreas. If the mean glucose gets too high, it treats more aggressively; and if glucose is too low, it becomes less aggressive.”
The average amount of insulin used per day was similar (0.62 U/kg vs. 0.66 U/kg) and the average amount of glucagon used was 0.5 mg/day in each group.
During the night, the bionic pancreas kept mean blood glucose lower (134 mg/dL vs. 165 mg/dL) and more stable, reducing time in hypoglycemia (1.4 minutes/night vs. 4.8 minutes/night).
There was one incident of severe hypoglycemia in the usual-care arm, and none in the bionic-pancreas arm. There was a statistically significant increase in nausea associated with the glucagon, Dr. Russell noted, but the impact was still quite small. On a 0-10 rating scale, nausea in the bionic pancreas group was rated a 0.5 compared to a 0.05 in the usual care arm.
There were no changes in blood pressure, weight, or any lab test.
The ongoing studies continue to show “that automated bihormonal control of glycemia in the home-use setting is feasible,” Dr. Russell said. “Micro-dose glucagon was well tolerated and the bihormonal pancreas reduced both mean glucose and hypoglycemia relative to the patients’ usual care devices.”
The iLet continues to undergo modifications that are making it more user friendly, he added.
Dr. Stevens disclosed that he has a patent pending on “certain aspects” of the device, and that he is an unpaid scientific consultant for Beta Bionics. He also disclosed financial relationships with several pharmaceutical and device companies, including Eli Lilly and Medtronic.
MUNICH – A “bionic pancreas” that delivers glucagon as well as insulin fared well against conventional insulin pump therapy, significantly reducing mean glucose levels and minimizing time spent in hypoglycemia.
The iLet bionic pancreas is being developed by Beta Bionics in conjunction with Eli Lilly and with support from the National Institutes of Health. Beta Bionics bills itself as a public benefit corporation – “a for-profit entity also dedicated to social responsibility and a public benefit mission,” according to an article published by Boston University.
Glucagon is the key that takes the bionic pancreas above and beyond what current insulin pump systems can do, said Dr. Russell, an endocrinologist at Massachusetts General Hospital, Boston.
“Even the pancreas, which has all the advantages of releasing insulin right into the portal vein and directly sensing glucose in the blood, uses the countering hormone, glucagon, to prevent hypoglycemia, particularly during exercise and in the late postprandial phase,” he said. “We are trying to mimic that capability. Glucagon gives us an additional tool to further reduce the risk of hypoglycemia.”
The algorithm is almost completely independent of user input – another key benefit, Dr. Russell said. It initializes with input about the patient’s weight and adapts its insulin delivery by essentially learning each user. There is no need to count carbohydrates, for example. The system “learns” over time its user’s typical meal patterns and can be programmed to deliver insulin accordingly.
“The user can enter, for example, ‘typical lunch,’ and the system will dispense some insulin before the meal and the rest later, in automatic delivery mode.”
The iLet has been studied in several settings and populations including, most recently, a successful crossover trial in 19 children at a diabetes camp (Lancet Diabetes Endocrinol. 2016; 4[3]:233-43).
The device was similarly successful in both teens and adults.
The study Dr. Russell reported at EASD 2016 comprised 39 patients with type 1 diabetes who were using an insulin pump. The mean age of the patients was 33 years, and mean disease duration was 17 years. The mean daily insulin dose was 0.6 U/kg. The mean baseline hemoglobin A1c was 7.7% and mean blood glucose, 176 mg/dL.
The crossover trial randomized patients to 11 days of treatment with their existing Medtronic insulin pump or the iLet system. The primary outcomes were the mean glucose level and time spent in hypoglycemic range (less than 60 mg/dL).
Under the usual care arm, “We saw a wide range of glucose values, which became much tighter when patients were using the bionic pancreas,” Dr. Russell said.
The overall average glucose level was 9 mmol/L in the usual care arm vs. 7.8 mmol/L in the bionic pancreas arm. Time in hypoglycemia was significantly reduced (27 minutes/24 hours vs. 9 minutes/24 hours).
“The standard deviation of the mean glucose was also larger in usual care, which is consistent with the automatic adaptive function of the bionic pancreas. If the mean glucose gets too high, it treats more aggressively; and if glucose is too low, it becomes less aggressive.”
The average amount of insulin used per day was similar (0.62 U/kg vs. 0.66 U/kg) and the average amount of glucagon used was 0.5 mg/day in each group.
During the night, the bionic pancreas kept mean blood glucose lower (134 mg/dL vs. 165 mg/dL) and more stable, reducing time in hypoglycemia (1.4 minutes/night vs. 4.8 minutes/night).
There was one incident of severe hypoglycemia in the usual-care arm, and none in the bionic-pancreas arm. There was a statistically significant increase in nausea associated with the glucagon, Dr. Russell noted, but the impact was still quite small. On a 0-10 rating scale, nausea in the bionic pancreas group was rated a 0.5 compared to a 0.05 in the usual care arm.
There were no changes in blood pressure, weight, or any lab test.
The ongoing studies continue to show “that automated bihormonal control of glycemia in the home-use setting is feasible,” Dr. Russell said. “Micro-dose glucagon was well tolerated and the bihormonal pancreas reduced both mean glucose and hypoglycemia relative to the patients’ usual care devices.”
The iLet continues to undergo modifications that are making it more user friendly, he added.
Dr. Stevens disclosed that he has a patent pending on “certain aspects” of the device, and that he is an unpaid scientific consultant for Beta Bionics. He also disclosed financial relationships with several pharmaceutical and device companies, including Eli Lilly and Medtronic.
Key clinical point:
Major finding: The overall average glucose level was 9 mmol/L in the usual care arm vs. 7.8 mmol/L in the bionic pancreas arm.
Data source: The randomized crossover trial comprised 39 patients with type 1 diabetes.
Disclosures: Dr. Stevens disclosed that he has a patent pending on “certain aspects” of the device and that he is an unpaid scientific consultant for Beta Bionics. He disclosed financial relationships with several pharmaceutical and device companies, including Eli Lilly and Medtronic.
Genes that drive glucose levels also drive heart disease
MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.
The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.
“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”
It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).
However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).
“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.
To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.
MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A1c. The project includes data on 133,000 subjects without type 2 diabetes.
They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.
MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.
He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.
In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.
A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).
The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.
Dr. Merino had no financial disclosures.
MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.
The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.
“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”
It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).
However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).
“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.
To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.
MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A1c. The project includes data on 133,000 subjects without type 2 diabetes.
They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.
MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.
He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.
In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.
A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).
The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.
Dr. Merino had no financial disclosures.
MUNICH – A group of 12 genes that influence blood sugar appears to help drive the risk of heart disease, independent of type 2 diabetes.
The genome-wide association study determined that every 1 mmol/L increase in fasting glucose associated with these genes increased the risk of coronary heart disease by 43%, Jordi Merino, PhD, said at the annual meeting of the European Association for the Study of Diabetes.
“Our results quantify the causal relationship between isolated, genetically increased fasting glucose and heart disease risk beyond the genetic effect of type 2 diabetes,” said Dr. Merino of Massachusetts General Hospital, Boston. “They suggest that modulating glycemia may provide cardiovascular benefit.”
It’s known that patients with type 2 diabetes have a higher incidence of coronary heart disease, even after accounting for traditional cardiovascular risk factors, he said. But five large prospective randomized studies – including the much-vaunted ACCORD – failed to find convincing evidence that managing blood glucose in patients with diabetes exerts any benefit on cardiovascular outcomes. In fact, patients assigned to intensive management (blood glucose targeted to below 6%) had a relative increase in all-cause mortality of 22% and an absolute increase of 1%, without any differences in cardiovascular mortality (5% vs. 4%; hazard ratio, 1.22) (N Engl J Med. 2008;358:2545-59).
However, a 2014 subanalysis of ACCORD found that outcomes for ischemic heart disease were significantly better in the intensively managed group. There was a 20% reduction in the risk of heart attack; a 19% reduction in a combined endpoint of heart attack; and similar reductions in the risk of coronary revascularization and unstable angina (Lancet. 2014;384:1936-41).
“We believed genetics might help to answer the question about this discrepancies in findings,” Dr. Merino said.
To investigate this, he and his colleagues plumbed the largest meta-analyses of genome-wide association studies of glucose and insulin regulation. MAGIC (the Meta-Analyses of Glucose and Insulin-related traits Consortium) is a collaborative effort that has combined genetic data from 55 studies.
MAGIC investigators have identified dozens of loci that influence levels of fasting glucose, fasting insulin, and hemoglobin A1c. The project includes data on 133,000 subjects without type 2 diabetes.
They used these data to conduct a Mendelian randomization analysis – a way of establishing causality between a specific gene and a specific clinical trait. Such an analysis is valid only when there are no other functional pathways between the genetic variant and the outcome and when confounding factors that could also affect the outcome can be controlled for.
MAGIC found 234 genetic variants that influence fasting glucose. Some of these also increase the risk of type 2 diabetes; after excluding those, Dr. Merino was left with 107 candidate genes. A disequilibrium analysis further pruned the group, leaving 12 genes that are independently associated with fasting glucose regulation.
He and his colleagues then applied data from the CARDIoGRAMplusC4D Consortium, which is searching for multiple risk loci for coronary artery disease and myocardial infarction in several large genetic studies. They created a five-level risk score for the glycemia-modulating genes and used to it determine how much genetically driven glucose variability affected the risk of heart disease in 5,000 subjects included in the Framingham Heart Study. The analysis controlled for lipids, blood pressure, and body mass index, he noted.
In a model that included all 12 of the variants, the investigators found that every 1 mmol/L increase in fasting glucose was associated with a significant 43% increase in the risk of heart disease.
A second analysis excluded one of the genes, but the significant association with increased risk of heart disease was preserved, at 34% per 1 mmol/L increase in fasting glucose. Individually, 10 of the genes raised the risk of coronary heart disease from a low of 6% (OR 1.06) to a high of almost 400% (OR 3.8).
The final pleiotropic analysis excluded all genes that could have more than one effect on heart disease; five genes survived to this level. Overall, they raised the risk of heart disease by 33%. Individually, the relative increased risks ranged from a low of 12% (odds ratio, 1.12) to a high of 87% (OR, 1.87). One gene was associated with a 25% risk reduction.
Dr. Merino had no financial disclosures.
AT EASD 2016
Key clinical point: Twelve newly identified genes associated with glucose levels appear to be independent drivers of coronary heart disease.
Major finding: Altogether, the constellation of genes raises the risk of heart disease by 43% for every 1 mmol/L increase in blood glucose.
Data source: Analysis of 133,000 subjects without diabetes.
Disclosures: Dr. Merino had no financial disclosures.
Aspirin not prescribed appropriately to cut cardiovascular risk in diabetes
MUNICH – Many patients with diabetes who could benefit from low-dose aspirin therapy may not be getting it – and many who are getting aspirin should not be, according to data presented at the annual meeting of the European Association for the Study of Diabetes.
A large, randomized trial concluded that 21% of diabetes patients who qualified for aspirin therapy for cardiovascular risk reduction were not getting it, and that it was contraindicated in almost 60% of those who were taking it, Lauren Crain, PhD, reported at the meeting.
Balancing the risks and benefits of aspirin therapy is not an easy challenge, said Dr. Crain, a health behavior researcher at HealthPartners Institute, Minneapolis. The clinical information necessary for the assessment is “rather lengthy, and not always readily available in primary care settings,” she said, and it’s clear from this study that clinicians could use some help in this area. Unfortunately, the electronic algorithm tested, which was meant to improve appropriate aspirin prescribing, didn’t improve the situation very much.
“At the final visit in the diabetes group [after the algorithm was employed], the total proportion of patients using aspirin was higher than at the first visit,” Dr. Crain noted. “However, that was the case regardless of whether patients were over- or underusing aspirin at the first visit.”
The aspirin findings were part of a large, randomized trial testing the algorithm as a way to reduce cardiovascular risk factors. The study was conducted in 19 primary care practices.
The decision-making algorithm, Cardiovascular Wizard, uses electronic health records to identify and advise patients with uncontrolled cardiovascular risk factors. Priorities and clinical recommendations are displayed for the provider and patient in the hope of facilitating shared decision making, Dr. Crain said.
One of the Wizard’s algorithms concerns aspirin prescribing. It is programmed with data from the United States Preventive Services Task Force, and recommends aspirin if cardiovascular risk scores are high and if consistent with providing a benefit greater than the risk of gastrointestinal bleeding. Aspirin is not recommended if the benefit is determined to be low or if major contraindications are present, including anticoagulant use or history of intracerebral hemorrhage.
The tool also alerts providers to the presence of other potential risks including aspirin allergy or intolerance, history of GI bleeds or risk conditions, and the concomitant use of nonsteroidal anti-inflammatory drugs.
The study comprised 11,000 adults, 4,000 of whom had diabetes. The remainder had high-risk, reversible cardiovascular risk factors (hypertension, dyslipidemia, or tobacco use). Each group was randomized to either cardiovascular risk assessment by usual care or with the Cardiovascular Wizard program.
The aspirin substudy looked at aspirin use at the baseline visit and the patient’s final, 1-year follow-up visit. At both visits, aspirin use was documented, and the clinician used the Wizard to assess whether or not it was indicated.
At the baseline visit, 71% of the diabetes group was using aspirin. However, according to the Wizard tool, more than one-third of them should not have been taking it – and among these, 57% were doing so. Among the remaining two-thirds of patients, all of whom should have been using aspirin, 21% were not taking it, Dr. Crain said.
Among the patients with reversible high-risk factors, 27% were using aspirin. However, according to the Wizard tool, the drug was contraindicated in 34% of those patients. “Most importantly, however, among those for whom aspirin was indicated, only 25% were using it – so, we’re talking about a 75% underusage,” Dr. Crain said.
By the 1-year follow-up visit, the situation was not much changed, despite the tool’s recommendations. Among those with diabetes, 56% in the usual care group and 60% in Wizard group were still overusing aspirin. Underuse was occurring in 21% of the usual care group and 17% of the Wizard group.
Patients with reversible high-risk factors fared a little better at 1 year, especially those who, at baseline, should have been taking aspirin but were not. Among these, 10% in the usual care group and 13% in the Wizard group had started taking aspirin.
The results were a bit of a disappointment, Dr. Crain said, but they don’t invalidate the investigators’ faith in an algorithmic advising system.
“We do think that electronic health record tools like this can help providers follow guidelines and improve the quality of their aspirin recommendations and prescribing, and hopefully reduce cardiovascular events and aspirin-related hazards,” she said. “Unfortunately, that didn’t happen here in the diabetes patients,” and the results in the second group were not stellar.
She added that the Wizard development team will be tweaking the tool to clarify some of the choices available as it guides patients and providers through the algorithm, in hopes of improving its efficacy.
Dr. Crain made no financial disclosures.
On Twitter @alz_gal
MUNICH – Many patients with diabetes who could benefit from low-dose aspirin therapy may not be getting it – and many who are getting aspirin should not be, according to data presented at the annual meeting of the European Association for the Study of Diabetes.
A large, randomized trial concluded that 21% of diabetes patients who qualified for aspirin therapy for cardiovascular risk reduction were not getting it, and that it was contraindicated in almost 60% of those who were taking it, Lauren Crain, PhD, reported at the meeting.
Balancing the risks and benefits of aspirin therapy is not an easy challenge, said Dr. Crain, a health behavior researcher at HealthPartners Institute, Minneapolis. The clinical information necessary for the assessment is “rather lengthy, and not always readily available in primary care settings,” she said, and it’s clear from this study that clinicians could use some help in this area. Unfortunately, the electronic algorithm tested, which was meant to improve appropriate aspirin prescribing, didn’t improve the situation very much.
“At the final visit in the diabetes group [after the algorithm was employed], the total proportion of patients using aspirin was higher than at the first visit,” Dr. Crain noted. “However, that was the case regardless of whether patients were over- or underusing aspirin at the first visit.”
The aspirin findings were part of a large, randomized trial testing the algorithm as a way to reduce cardiovascular risk factors. The study was conducted in 19 primary care practices.
The decision-making algorithm, Cardiovascular Wizard, uses electronic health records to identify and advise patients with uncontrolled cardiovascular risk factors. Priorities and clinical recommendations are displayed for the provider and patient in the hope of facilitating shared decision making, Dr. Crain said.
One of the Wizard’s algorithms concerns aspirin prescribing. It is programmed with data from the United States Preventive Services Task Force, and recommends aspirin if cardiovascular risk scores are high and if consistent with providing a benefit greater than the risk of gastrointestinal bleeding. Aspirin is not recommended if the benefit is determined to be low or if major contraindications are present, including anticoagulant use or history of intracerebral hemorrhage.
The tool also alerts providers to the presence of other potential risks including aspirin allergy or intolerance, history of GI bleeds or risk conditions, and the concomitant use of nonsteroidal anti-inflammatory drugs.
The study comprised 11,000 adults, 4,000 of whom had diabetes. The remainder had high-risk, reversible cardiovascular risk factors (hypertension, dyslipidemia, or tobacco use). Each group was randomized to either cardiovascular risk assessment by usual care or with the Cardiovascular Wizard program.
The aspirin substudy looked at aspirin use at the baseline visit and the patient’s final, 1-year follow-up visit. At both visits, aspirin use was documented, and the clinician used the Wizard to assess whether or not it was indicated.
At the baseline visit, 71% of the diabetes group was using aspirin. However, according to the Wizard tool, more than one-third of them should not have been taking it – and among these, 57% were doing so. Among the remaining two-thirds of patients, all of whom should have been using aspirin, 21% were not taking it, Dr. Crain said.
Among the patients with reversible high-risk factors, 27% were using aspirin. However, according to the Wizard tool, the drug was contraindicated in 34% of those patients. “Most importantly, however, among those for whom aspirin was indicated, only 25% were using it – so, we’re talking about a 75% underusage,” Dr. Crain said.
By the 1-year follow-up visit, the situation was not much changed, despite the tool’s recommendations. Among those with diabetes, 56% in the usual care group and 60% in Wizard group were still overusing aspirin. Underuse was occurring in 21% of the usual care group and 17% of the Wizard group.
Patients with reversible high-risk factors fared a little better at 1 year, especially those who, at baseline, should have been taking aspirin but were not. Among these, 10% in the usual care group and 13% in the Wizard group had started taking aspirin.
The results were a bit of a disappointment, Dr. Crain said, but they don’t invalidate the investigators’ faith in an algorithmic advising system.
“We do think that electronic health record tools like this can help providers follow guidelines and improve the quality of their aspirin recommendations and prescribing, and hopefully reduce cardiovascular events and aspirin-related hazards,” she said. “Unfortunately, that didn’t happen here in the diabetes patients,” and the results in the second group were not stellar.
She added that the Wizard development team will be tweaking the tool to clarify some of the choices available as it guides patients and providers through the algorithm, in hopes of improving its efficacy.
Dr. Crain made no financial disclosures.
On Twitter @alz_gal
MUNICH – Many patients with diabetes who could benefit from low-dose aspirin therapy may not be getting it – and many who are getting aspirin should not be, according to data presented at the annual meeting of the European Association for the Study of Diabetes.
A large, randomized trial concluded that 21% of diabetes patients who qualified for aspirin therapy for cardiovascular risk reduction were not getting it, and that it was contraindicated in almost 60% of those who were taking it, Lauren Crain, PhD, reported at the meeting.
Balancing the risks and benefits of aspirin therapy is not an easy challenge, said Dr. Crain, a health behavior researcher at HealthPartners Institute, Minneapolis. The clinical information necessary for the assessment is “rather lengthy, and not always readily available in primary care settings,” she said, and it’s clear from this study that clinicians could use some help in this area. Unfortunately, the electronic algorithm tested, which was meant to improve appropriate aspirin prescribing, didn’t improve the situation very much.
“At the final visit in the diabetes group [after the algorithm was employed], the total proportion of patients using aspirin was higher than at the first visit,” Dr. Crain noted. “However, that was the case regardless of whether patients were over- or underusing aspirin at the first visit.”
The aspirin findings were part of a large, randomized trial testing the algorithm as a way to reduce cardiovascular risk factors. The study was conducted in 19 primary care practices.
The decision-making algorithm, Cardiovascular Wizard, uses electronic health records to identify and advise patients with uncontrolled cardiovascular risk factors. Priorities and clinical recommendations are displayed for the provider and patient in the hope of facilitating shared decision making, Dr. Crain said.
One of the Wizard’s algorithms concerns aspirin prescribing. It is programmed with data from the United States Preventive Services Task Force, and recommends aspirin if cardiovascular risk scores are high and if consistent with providing a benefit greater than the risk of gastrointestinal bleeding. Aspirin is not recommended if the benefit is determined to be low or if major contraindications are present, including anticoagulant use or history of intracerebral hemorrhage.
The tool also alerts providers to the presence of other potential risks including aspirin allergy or intolerance, history of GI bleeds or risk conditions, and the concomitant use of nonsteroidal anti-inflammatory drugs.
The study comprised 11,000 adults, 4,000 of whom had diabetes. The remainder had high-risk, reversible cardiovascular risk factors (hypertension, dyslipidemia, or tobacco use). Each group was randomized to either cardiovascular risk assessment by usual care or with the Cardiovascular Wizard program.
The aspirin substudy looked at aspirin use at the baseline visit and the patient’s final, 1-year follow-up visit. At both visits, aspirin use was documented, and the clinician used the Wizard to assess whether or not it was indicated.
At the baseline visit, 71% of the diabetes group was using aspirin. However, according to the Wizard tool, more than one-third of them should not have been taking it – and among these, 57% were doing so. Among the remaining two-thirds of patients, all of whom should have been using aspirin, 21% were not taking it, Dr. Crain said.
Among the patients with reversible high-risk factors, 27% were using aspirin. However, according to the Wizard tool, the drug was contraindicated in 34% of those patients. “Most importantly, however, among those for whom aspirin was indicated, only 25% were using it – so, we’re talking about a 75% underusage,” Dr. Crain said.
By the 1-year follow-up visit, the situation was not much changed, despite the tool’s recommendations. Among those with diabetes, 56% in the usual care group and 60% in Wizard group were still overusing aspirin. Underuse was occurring in 21% of the usual care group and 17% of the Wizard group.
Patients with reversible high-risk factors fared a little better at 1 year, especially those who, at baseline, should have been taking aspirin but were not. Among these, 10% in the usual care group and 13% in the Wizard group had started taking aspirin.
The results were a bit of a disappointment, Dr. Crain said, but they don’t invalidate the investigators’ faith in an algorithmic advising system.
“We do think that electronic health record tools like this can help providers follow guidelines and improve the quality of their aspirin recommendations and prescribing, and hopefully reduce cardiovascular events and aspirin-related hazards,” she said. “Unfortunately, that didn’t happen here in the diabetes patients,” and the results in the second group were not stellar.
She added that the Wizard development team will be tweaking the tool to clarify some of the choices available as it guides patients and providers through the algorithm, in hopes of improving its efficacy.
Dr. Crain made no financial disclosures.
On Twitter @alz_gal
AT EASD 2016
Key clinical point: Many diabetes patients who should be taking aspirin for cardiovascular risk reduction are not doing so, and many who should not be taking it are.
Major finding: Aspirin was underused in 21% of diabetes patients and overused in 57% of patients.
Data source: A randomized study of 11,000 patients.
Disclosures: Dr. Lauren Crain had no financial disclosures.
Adding foot screening to eye clinic catches diabetic neuropathy
MUNICH – A combined eye, foot, and renal screening clinic identified undiagnosed painful diabetic neuropathy in 12% of diabetic patients who attended.
The clinic in Sheffield, England, was well attended and well liked, with 85% patient approval. The patients appreciated that the visit assured attention to their feet and also let them combine several individual clinic visits for diabetes complications screening, Solomon Tesfaye, MD, said at the annual meeting of the European Association for the Study of Diabetes.
“Twenty percent of our attendants said they had never even had a foot exam before,” said Dr. Tesfaye, an endocrinologist at the University of Sheffield. “And almost half had never had any kind of diabetic foot education.”
Dr. Tesfaye said this lack of attention to foot care in diabetes patients in the United Kingdom is “completely unacceptable.” The country is facing an epidemic of diabetes-related foot amputations, he said.
“We have unacceptable numbers of amputations, on the order of 135 each week, and unfortunately that number is rising. Why is that? Because in the U.K., we tend to diagnose diabetic neuropathy mainly with the 10-g monofilament test, because that is reimbursed. And while it’s a good way of screening for foot ulceration risk, it’s not a good model of diagnosing neuropathy early. So we are now unfortunately diagnosing it late, when it’s advanced and completely irreversible.”
The consequences of foot damage are far-reaching, Dr. Tesfaye said. “Patients who have to be referred into a foot clinic have very high mortality, approaching 50% at 5 years. In the U.K., we’re adding more and more foot clinics every year, and this is not a measure of success. It’s a measure of failure.”
Diabetic retinopathy, however, is the country’s good news story. More than 90% of people – diabetic or not – attend an annual eye screening as part of their wellness visits. As a result, diabetic eye disease is no longer the leading cause of blindness in adults in the United Kingdom.
“Everyone attends this annual eye screening, which uses retinal photography, and anyone with early changes is referred to specialist care,” Dr. Tesfaye said. “This has resulted in a paradigm shift in blindness, and that’s fantastic news.”
It just made sense, he said, to use the popular eye screening visit as a chance to also intervene early in undiagnosed diabetic neuropathy. A recent German study underscored the importance of early intervention (Diabetes 2014 Jul;63[7]:2454-63).
This study demonstrated that intraepidermal nerve fibers were already significantly reduced in 20% of patients within a year of their diabetes diagnosis. Nerve conduction values and amplitude were already impacted as well.
“The neuropathic process starts early, but we are using very insensitive measures to diagnose it,” Dr. Tesfaye said.
The combination clinic used several devices to test nerve function in feet, in addition to the 10-g monofilament test:
• A handheld device called DPN-Check, which measures sural nerve conduction velocity and response amplitude.
• Sudoscan, which measures sudomotor dysfunction – one of the earliest neurophysiologic changes in distal small fiber neuropathies.
• The Toronto Clinical Scoring System, a clinical tool that assesses symptoms, reflexes, and sensory function.
The entire foot exam takes 15 minutes and is done after the patient receives the eyedrops necessary for the ocular exam. The renal screening consists of a blood draw for tests of renal function.
The study group comprised 180 patients, with a mean age of 64 years. Type 1 diabetes was present in 6%; the rest had type 2 disease.
The Toronto score was 5 or higher, indicating the presence of diabetic neuropathy, in almost 32%.
The Sudoscan identified small nerve dysfunction consistent with neuropathy in 40%. The DPN-Check score identified neuropathy in 55%. However, the monofilament test was positive in 12%.
In addition to the increased number of neuropathy patients identified, “we also had new diagnoses of painful diabetic neuropathy in about 12% of the group,” Dr. Tesfaye said.
The devices had very good individual diagnostic accuracy, and when the devices were combined, the results were “really staggering,” he said. The Sudoscan alone had a sensitivity of 79% and a specificity of 60%; the DPN-Check alone, a sensitivity of 91% and a specificity of 73%. But when combined, the two diagnostic tools yielded an overall sensitivity of 94% and specificity of 63%. This correlated very well with the Toronto Clinical Scoring System, he added.
“It’s obvious that the 10-g monofilament test grossly underestimated the true presence of diabetic neuropathy. But using these combined point-of-care devices, we were able to detect it with an extremely high sensitivity. This service enables our patients to be referred early to podiatric services. Whether this early referral will result in the reversal of these neuropathic changes is yet to be determined.”
Dr. Tesfaye reported relationships with NeuroMetrix, Impeto Medical, Eli Lilly, Pfizer, Worwag Pharma, and TRIGOcare International.
MUNICH – A combined eye, foot, and renal screening clinic identified undiagnosed painful diabetic neuropathy in 12% of diabetic patients who attended.
The clinic in Sheffield, England, was well attended and well liked, with 85% patient approval. The patients appreciated that the visit assured attention to their feet and also let them combine several individual clinic visits for diabetes complications screening, Solomon Tesfaye, MD, said at the annual meeting of the European Association for the Study of Diabetes.
“Twenty percent of our attendants said they had never even had a foot exam before,” said Dr. Tesfaye, an endocrinologist at the University of Sheffield. “And almost half had never had any kind of diabetic foot education.”
Dr. Tesfaye said this lack of attention to foot care in diabetes patients in the United Kingdom is “completely unacceptable.” The country is facing an epidemic of diabetes-related foot amputations, he said.
“We have unacceptable numbers of amputations, on the order of 135 each week, and unfortunately that number is rising. Why is that? Because in the U.K., we tend to diagnose diabetic neuropathy mainly with the 10-g monofilament test, because that is reimbursed. And while it’s a good way of screening for foot ulceration risk, it’s not a good model of diagnosing neuropathy early. So we are now unfortunately diagnosing it late, when it’s advanced and completely irreversible.”
The consequences of foot damage are far-reaching, Dr. Tesfaye said. “Patients who have to be referred into a foot clinic have very high mortality, approaching 50% at 5 years. In the U.K., we’re adding more and more foot clinics every year, and this is not a measure of success. It’s a measure of failure.”
Diabetic retinopathy, however, is the country’s good news story. More than 90% of people – diabetic or not – attend an annual eye screening as part of their wellness visits. As a result, diabetic eye disease is no longer the leading cause of blindness in adults in the United Kingdom.
“Everyone attends this annual eye screening, which uses retinal photography, and anyone with early changes is referred to specialist care,” Dr. Tesfaye said. “This has resulted in a paradigm shift in blindness, and that’s fantastic news.”
It just made sense, he said, to use the popular eye screening visit as a chance to also intervene early in undiagnosed diabetic neuropathy. A recent German study underscored the importance of early intervention (Diabetes 2014 Jul;63[7]:2454-63).
This study demonstrated that intraepidermal nerve fibers were already significantly reduced in 20% of patients within a year of their diabetes diagnosis. Nerve conduction values and amplitude were already impacted as well.
“The neuropathic process starts early, but we are using very insensitive measures to diagnose it,” Dr. Tesfaye said.
The combination clinic used several devices to test nerve function in feet, in addition to the 10-g monofilament test:
• A handheld device called DPN-Check, which measures sural nerve conduction velocity and response amplitude.
• Sudoscan, which measures sudomotor dysfunction – one of the earliest neurophysiologic changes in distal small fiber neuropathies.
• The Toronto Clinical Scoring System, a clinical tool that assesses symptoms, reflexes, and sensory function.
The entire foot exam takes 15 minutes and is done after the patient receives the eyedrops necessary for the ocular exam. The renal screening consists of a blood draw for tests of renal function.
The study group comprised 180 patients, with a mean age of 64 years. Type 1 diabetes was present in 6%; the rest had type 2 disease.
The Toronto score was 5 or higher, indicating the presence of diabetic neuropathy, in almost 32%.
The Sudoscan identified small nerve dysfunction consistent with neuropathy in 40%. The DPN-Check score identified neuropathy in 55%. However, the monofilament test was positive in 12%.
In addition to the increased number of neuropathy patients identified, “we also had new diagnoses of painful diabetic neuropathy in about 12% of the group,” Dr. Tesfaye said.
The devices had very good individual diagnostic accuracy, and when the devices were combined, the results were “really staggering,” he said. The Sudoscan alone had a sensitivity of 79% and a specificity of 60%; the DPN-Check alone, a sensitivity of 91% and a specificity of 73%. But when combined, the two diagnostic tools yielded an overall sensitivity of 94% and specificity of 63%. This correlated very well with the Toronto Clinical Scoring System, he added.
“It’s obvious that the 10-g monofilament test grossly underestimated the true presence of diabetic neuropathy. But using these combined point-of-care devices, we were able to detect it with an extremely high sensitivity. This service enables our patients to be referred early to podiatric services. Whether this early referral will result in the reversal of these neuropathic changes is yet to be determined.”
Dr. Tesfaye reported relationships with NeuroMetrix, Impeto Medical, Eli Lilly, Pfizer, Worwag Pharma, and TRIGOcare International.
MUNICH – A combined eye, foot, and renal screening clinic identified undiagnosed painful diabetic neuropathy in 12% of diabetic patients who attended.
The clinic in Sheffield, England, was well attended and well liked, with 85% patient approval. The patients appreciated that the visit assured attention to their feet and also let them combine several individual clinic visits for diabetes complications screening, Solomon Tesfaye, MD, said at the annual meeting of the European Association for the Study of Diabetes.
“Twenty percent of our attendants said they had never even had a foot exam before,” said Dr. Tesfaye, an endocrinologist at the University of Sheffield. “And almost half had never had any kind of diabetic foot education.”
Dr. Tesfaye said this lack of attention to foot care in diabetes patients in the United Kingdom is “completely unacceptable.” The country is facing an epidemic of diabetes-related foot amputations, he said.
“We have unacceptable numbers of amputations, on the order of 135 each week, and unfortunately that number is rising. Why is that? Because in the U.K., we tend to diagnose diabetic neuropathy mainly with the 10-g monofilament test, because that is reimbursed. And while it’s a good way of screening for foot ulceration risk, it’s not a good model of diagnosing neuropathy early. So we are now unfortunately diagnosing it late, when it’s advanced and completely irreversible.”
The consequences of foot damage are far-reaching, Dr. Tesfaye said. “Patients who have to be referred into a foot clinic have very high mortality, approaching 50% at 5 years. In the U.K., we’re adding more and more foot clinics every year, and this is not a measure of success. It’s a measure of failure.”
Diabetic retinopathy, however, is the country’s good news story. More than 90% of people – diabetic or not – attend an annual eye screening as part of their wellness visits. As a result, diabetic eye disease is no longer the leading cause of blindness in adults in the United Kingdom.
“Everyone attends this annual eye screening, which uses retinal photography, and anyone with early changes is referred to specialist care,” Dr. Tesfaye said. “This has resulted in a paradigm shift in blindness, and that’s fantastic news.”
It just made sense, he said, to use the popular eye screening visit as a chance to also intervene early in undiagnosed diabetic neuropathy. A recent German study underscored the importance of early intervention (Diabetes 2014 Jul;63[7]:2454-63).
This study demonstrated that intraepidermal nerve fibers were already significantly reduced in 20% of patients within a year of their diabetes diagnosis. Nerve conduction values and amplitude were already impacted as well.
“The neuropathic process starts early, but we are using very insensitive measures to diagnose it,” Dr. Tesfaye said.
The combination clinic used several devices to test nerve function in feet, in addition to the 10-g monofilament test:
• A handheld device called DPN-Check, which measures sural nerve conduction velocity and response amplitude.
• Sudoscan, which measures sudomotor dysfunction – one of the earliest neurophysiologic changes in distal small fiber neuropathies.
• The Toronto Clinical Scoring System, a clinical tool that assesses symptoms, reflexes, and sensory function.
The entire foot exam takes 15 minutes and is done after the patient receives the eyedrops necessary for the ocular exam. The renal screening consists of a blood draw for tests of renal function.
The study group comprised 180 patients, with a mean age of 64 years. Type 1 diabetes was present in 6%; the rest had type 2 disease.
The Toronto score was 5 or higher, indicating the presence of diabetic neuropathy, in almost 32%.
The Sudoscan identified small nerve dysfunction consistent with neuropathy in 40%. The DPN-Check score identified neuropathy in 55%. However, the monofilament test was positive in 12%.
In addition to the increased number of neuropathy patients identified, “we also had new diagnoses of painful diabetic neuropathy in about 12% of the group,” Dr. Tesfaye said.
The devices had very good individual diagnostic accuracy, and when the devices were combined, the results were “really staggering,” he said. The Sudoscan alone had a sensitivity of 79% and a specificity of 60%; the DPN-Check alone, a sensitivity of 91% and a specificity of 73%. But when combined, the two diagnostic tools yielded an overall sensitivity of 94% and specificity of 63%. This correlated very well with the Toronto Clinical Scoring System, he added.
“It’s obvious that the 10-g monofilament test grossly underestimated the true presence of diabetic neuropathy. But using these combined point-of-care devices, we were able to detect it with an extremely high sensitivity. This service enables our patients to be referred early to podiatric services. Whether this early referral will result in the reversal of these neuropathic changes is yet to be determined.”
Dr. Tesfaye reported relationships with NeuroMetrix, Impeto Medical, Eli Lilly, Pfizer, Worwag Pharma, and TRIGOcare International.
AT EASD 2016
Key clinical point: The addition of diabetic foot screening to an eye clinic boosted the diagnosis of diabetic neuropathy.
Major finding: Painful diabetic neuropathy was diagnosed in 12% of those who attended.
Data source: A prospective study involving 180 patients.
Disclosures: Dr. Tesfaye disclosed relationships with numerous drug and device manufacturers.
Novel GLP-1 receptor agonist shows reduction in cardiovascular risk
The novel glucagonlike peptide 1 (GLP-1) receptor agonist semaglutide may reduce the risk of cardiovascular events in patients with type 2 diabetes who are at elevated cardiovascular risk, according to data presented Sept. 16 at the annual meeting of the European Association for the Study of Diabetes and simultaneously published online in the New England Journal of Medicine.
“In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide,” wrote Steven P. Marso, MD, and his coinvestigators.
SUSTAIN-6 was a randomized, placebo-controlled, noninferiority trial in which 3,297 patients with type 2 diabetes, 85% of whom had established cardiovascular disease, were assigned to take either once-weekly semaglutide (0.5 mg or 1 mg) or placebo.
At the end of the 2-year study period, patients on semaglutide had a statistically significant, 26% lower risk of first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, the study’s primary composite outcome, compared with those on placebo (P less than .001), Dr. Marso and his associates wrote. This outcome occurred in 108 of 1,648 patients (6.6%) in the semaglutide group and in 146 of 1,649 patients (8.9%) in the placebo group.
Specifically, the study showed a 26% reduction in the risk of nonfatal MI (P = .12) and 39% reduction in nonfatal stroke (P = .04) with semaglutide, while the rates of cardiovascular death and heart failure hospitalizations were similar between the two arms of the study.
Overall, 60.5% of the patients in the study had a history of cardiovascular disease, and nearly one-third had a history of MI (N Engl J Med. 2016 Sep 16. doi: 10.1056/NEJMoa1607141).
“In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide,” wrote Dr. Marso of the Research Medical Center in Kansas City, Mo., and coauthors. “The beneficial effect of semaglutide on cardiovascular outcomes may relate to modification of the progression of atherosclerosis.”
Semaglutide has a longer duration of action than the approved GLP-1 receptor agonists – liraglutide, exenatide, albiglutide, dulaglutide, and lixisenatide – allowing for once-weekly subcutaneous injection.
Patients enrolled in the study were all on a standard care regimen, but those taking semaglutide showed significant and sustained reductions in hemoglobin A1c levels, compared with placebo, as well as a higher incidence of clinically meaningful and sustained weight loss, and reductions in systolic blood pressure.
The reductions in HbA1c, body weight, and systolic blood pressure may all have contributed to the observed reduction in cardiovascular risk with semaglutide,” the authors noted.
The study did observe significantly higher rates of diabetic retinopathy complications in patients taking semaglutide. The overall incidence of these complications occurred in 50 patients (3.0%) in the semaglutide group and 29 (1.8%) of the placebo patients, yielding a hazard ratio of 1.76 (P = .02). More patients in the semaglutide group required retinal photocoagulation or the use of an intravitreal agent, had a vitreous hemorrhage, or had developed diabetes-related blindness.
However, patients taking semaglutide also had a 36% lower incidence of new or worsening nephropathy (P = .005), and the frequency of serious adverse events was also lower in the semaglutide group than in the placebo patients.
“With the exception of complications of retinopathy, semaglutide had a safety profile similar to that of other GLP-1 receptor agonists,” the authors reported. The rates of malignant neoplasms were similar in both arms of the study, and the rate of pancreatic cancer, which is known to be an event of interest for this class of drugs, was lower in the semaglutide arm, compared with placebo.
Semaglutide is in development and not yet approved for the treatment of type 2 diabetes.
Starting in 2008, all new drug applications to the Food and Drug Administration for antihyperglycemic agents must include evidence that therapy will not increase the risk of cardiovascular events; SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects with Type 2 Diabetes) was designed to fill that need for semaglutide, and is being developed by Novo Nordisk.
The study was supported by Novo Nordisk. Thirteen authors declared consultancies, grants, fees, and other support from pharmaceutical companies, including Novo Nordisk, and three authors were employees of Novo Nordisk.
SUSTAIN-6 is a carefully planned, well-performed, and objectively reported trial that showed a meaningful reduction in the cardiovascular endpoint of first occurrence of cardiovascular death, nonfatal MI, or stroke of 26%.
Comparing the HbA1c attained across cardiovascular outcome trials of other antihyperglycemic drugs, semaglutide was more efficient in SUSTAIN-6 than in the two cardiovascular outcome trials that have thus far shown cardiovascular benefit, LEADER (N Engl J Med. 2016;375:311-32) in liraglutide and EMPA-REG (N Engl J Med. 2015;373:2117-128) in empagliflozin, lowering HbA1c to 7.3, compared with 7.7 and 8.0, respectively.
 |
| Michele G. Sullivan Dr. Lars Rydén |
However, that doesn’t explain the greater absolute risk reduction in the primary outcome of 2.6% in SUSTAIN-6, compared with LEADER (1.9%) and EMPA-REG (1.6), even with a shorter trial duration. But duration of action may hold the key. Semaglutide has a half-life of 7 days, compared with 13 hours for liraglutide and roughly 4 hours for lixisenatide, so perhaps it’s very important to cover the full day before you start to get the impact.
Considering the slow onset of action and the impact on stroke, myocardial infarction, and revascularization, the delay of progress, or regression of atherosclerosis, is likely the important mechanism.
Dr. Lars Rydén is a cardiologist at the Karolinska Institute in Stockholm. He has received research support from Amgen, Bayer AG, Boehringer-Ingelheim, Merck, and Novo Nordisk, the developer of semaglutide. He made these comments as designated discussant for the SUSTAIN-6 report.
SUSTAIN-6 is a carefully planned, well-performed, and objectively reported trial that showed a meaningful reduction in the cardiovascular endpoint of first occurrence of cardiovascular death, nonfatal MI, or stroke of 26%.
Comparing the HbA1c attained across cardiovascular outcome trials of other antihyperglycemic drugs, semaglutide was more efficient in SUSTAIN-6 than in the two cardiovascular outcome trials that have thus far shown cardiovascular benefit, LEADER (N Engl J Med. 2016;375:311-32) in liraglutide and EMPA-REG (N Engl J Med. 2015;373:2117-128) in empagliflozin, lowering HbA1c to 7.3, compared with 7.7 and 8.0, respectively.
|
| Michele G. Sullivan Dr. Lars Rydén |
However, that doesn’t explain the greater absolute risk reduction in the primary outcome of 2.6% in SUSTAIN-6, compared with LEADER (1.9%) and EMPA-REG (1.6), even with a shorter trial duration. But duration of action may hold the key. Semaglutide has a half-life of 7 days, compared with 13 hours for liraglutide and roughly 4 hours for lixisenatide, so perhaps it’s very important to cover the full day before you start to get the impact.
Considering the slow onset of action and the impact on stroke, myocardial infarction, and revascularization, the delay of progress, or regression of atherosclerosis, is likely the important mechanism.
Dr. Lars Rydén is a cardiologist at the Karolinska Institute in Stockholm. He has received research support from Amgen, Bayer AG, Boehringer-Ingelheim, Merck, and Novo Nordisk, the developer of semaglutide. He made these comments as designated discussant for the SUSTAIN-6 report.
SUSTAIN-6 is a carefully planned, well-performed, and objectively reported trial that showed a meaningful reduction in the cardiovascular endpoint of first occurrence of cardiovascular death, nonfatal MI, or stroke of 26%.
Comparing the HbA1c attained across cardiovascular outcome trials of other antihyperglycemic drugs, semaglutide was more efficient in SUSTAIN-6 than in the two cardiovascular outcome trials that have thus far shown cardiovascular benefit, LEADER (N Engl J Med. 2016;375:311-32) in liraglutide and EMPA-REG (N Engl J Med. 2015;373:2117-128) in empagliflozin, lowering HbA1c to 7.3, compared with 7.7 and 8.0, respectively.
|
| Michele G. Sullivan Dr. Lars Rydén |
However, that doesn’t explain the greater absolute risk reduction in the primary outcome of 2.6% in SUSTAIN-6, compared with LEADER (1.9%) and EMPA-REG (1.6), even with a shorter trial duration. But duration of action may hold the key. Semaglutide has a half-life of 7 days, compared with 13 hours for liraglutide and roughly 4 hours for lixisenatide, so perhaps it’s very important to cover the full day before you start to get the impact.
Considering the slow onset of action and the impact on stroke, myocardial infarction, and revascularization, the delay of progress, or regression of atherosclerosis, is likely the important mechanism.
Dr. Lars Rydén is a cardiologist at the Karolinska Institute in Stockholm. He has received research support from Amgen, Bayer AG, Boehringer-Ingelheim, Merck, and Novo Nordisk, the developer of semaglutide. He made these comments as designated discussant for the SUSTAIN-6 report.
The novel glucagonlike peptide 1 (GLP-1) receptor agonist semaglutide may reduce the risk of cardiovascular events in patients with type 2 diabetes who are at elevated cardiovascular risk, according to data presented Sept. 16 at the annual meeting of the European Association for the Study of Diabetes and simultaneously published online in the New England Journal of Medicine.
“In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide,” wrote Steven P. Marso, MD, and his coinvestigators.
SUSTAIN-6 was a randomized, placebo-controlled, noninferiority trial in which 3,297 patients with type 2 diabetes, 85% of whom had established cardiovascular disease, were assigned to take either once-weekly semaglutide (0.5 mg or 1 mg) or placebo.
At the end of the 2-year study period, patients on semaglutide had a statistically significant, 26% lower risk of first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, the study’s primary composite outcome, compared with those on placebo (P less than .001), Dr. Marso and his associates wrote. This outcome occurred in 108 of 1,648 patients (6.6%) in the semaglutide group and in 146 of 1,649 patients (8.9%) in the placebo group.
Specifically, the study showed a 26% reduction in the risk of nonfatal MI (P = .12) and 39% reduction in nonfatal stroke (P = .04) with semaglutide, while the rates of cardiovascular death and heart failure hospitalizations were similar between the two arms of the study.
Overall, 60.5% of the patients in the study had a history of cardiovascular disease, and nearly one-third had a history of MI (N Engl J Med. 2016 Sep 16. doi: 10.1056/NEJMoa1607141).
“In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide,” wrote Dr. Marso of the Research Medical Center in Kansas City, Mo., and coauthors. “The beneficial effect of semaglutide on cardiovascular outcomes may relate to modification of the progression of atherosclerosis.”
Semaglutide has a longer duration of action than the approved GLP-1 receptor agonists – liraglutide, exenatide, albiglutide, dulaglutide, and lixisenatide – allowing for once-weekly subcutaneous injection.
Patients enrolled in the study were all on a standard care regimen, but those taking semaglutide showed significant and sustained reductions in hemoglobin A1c levels, compared with placebo, as well as a higher incidence of clinically meaningful and sustained weight loss, and reductions in systolic blood pressure.
The reductions in HbA1c, body weight, and systolic blood pressure may all have contributed to the observed reduction in cardiovascular risk with semaglutide,” the authors noted.
The study did observe significantly higher rates of diabetic retinopathy complications in patients taking semaglutide. The overall incidence of these complications occurred in 50 patients (3.0%) in the semaglutide group and 29 (1.8%) of the placebo patients, yielding a hazard ratio of 1.76 (P = .02). More patients in the semaglutide group required retinal photocoagulation or the use of an intravitreal agent, had a vitreous hemorrhage, or had developed diabetes-related blindness.
However, patients taking semaglutide also had a 36% lower incidence of new or worsening nephropathy (P = .005), and the frequency of serious adverse events was also lower in the semaglutide group than in the placebo patients.
“With the exception of complications of retinopathy, semaglutide had a safety profile similar to that of other GLP-1 receptor agonists,” the authors reported. The rates of malignant neoplasms were similar in both arms of the study, and the rate of pancreatic cancer, which is known to be an event of interest for this class of drugs, was lower in the semaglutide arm, compared with placebo.
Semaglutide is in development and not yet approved for the treatment of type 2 diabetes.
Starting in 2008, all new drug applications to the Food and Drug Administration for antihyperglycemic agents must include evidence that therapy will not increase the risk of cardiovascular events; SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects with Type 2 Diabetes) was designed to fill that need for semaglutide, and is being developed by Novo Nordisk.
The study was supported by Novo Nordisk. Thirteen authors declared consultancies, grants, fees, and other support from pharmaceutical companies, including Novo Nordisk, and three authors were employees of Novo Nordisk.
The novel glucagonlike peptide 1 (GLP-1) receptor agonist semaglutide may reduce the risk of cardiovascular events in patients with type 2 diabetes who are at elevated cardiovascular risk, according to data presented Sept. 16 at the annual meeting of the European Association for the Study of Diabetes and simultaneously published online in the New England Journal of Medicine.
“In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide,” wrote Steven P. Marso, MD, and his coinvestigators.
SUSTAIN-6 was a randomized, placebo-controlled, noninferiority trial in which 3,297 patients with type 2 diabetes, 85% of whom had established cardiovascular disease, were assigned to take either once-weekly semaglutide (0.5 mg or 1 mg) or placebo.
At the end of the 2-year study period, patients on semaglutide had a statistically significant, 26% lower risk of first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, the study’s primary composite outcome, compared with those on placebo (P less than .001), Dr. Marso and his associates wrote. This outcome occurred in 108 of 1,648 patients (6.6%) in the semaglutide group and in 146 of 1,649 patients (8.9%) in the placebo group.
Specifically, the study showed a 26% reduction in the risk of nonfatal MI (P = .12) and 39% reduction in nonfatal stroke (P = .04) with semaglutide, while the rates of cardiovascular death and heart failure hospitalizations were similar between the two arms of the study.
Overall, 60.5% of the patients in the study had a history of cardiovascular disease, and nearly one-third had a history of MI (N Engl J Med. 2016 Sep 16. doi: 10.1056/NEJMoa1607141).
“In patients with type 2 diabetes who were at high cardiovascular risk, the rate of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke was significantly lower among patients receiving semaglutide than among those receiving placebo, an outcome that confirmed the noninferiority of semaglutide,” wrote Dr. Marso of the Research Medical Center in Kansas City, Mo., and coauthors. “The beneficial effect of semaglutide on cardiovascular outcomes may relate to modification of the progression of atherosclerosis.”
Semaglutide has a longer duration of action than the approved GLP-1 receptor agonists – liraglutide, exenatide, albiglutide, dulaglutide, and lixisenatide – allowing for once-weekly subcutaneous injection.
Patients enrolled in the study were all on a standard care regimen, but those taking semaglutide showed significant and sustained reductions in hemoglobin A1c levels, compared with placebo, as well as a higher incidence of clinically meaningful and sustained weight loss, and reductions in systolic blood pressure.
The reductions in HbA1c, body weight, and systolic blood pressure may all have contributed to the observed reduction in cardiovascular risk with semaglutide,” the authors noted.
The study did observe significantly higher rates of diabetic retinopathy complications in patients taking semaglutide. The overall incidence of these complications occurred in 50 patients (3.0%) in the semaglutide group and 29 (1.8%) of the placebo patients, yielding a hazard ratio of 1.76 (P = .02). More patients in the semaglutide group required retinal photocoagulation or the use of an intravitreal agent, had a vitreous hemorrhage, or had developed diabetes-related blindness.
However, patients taking semaglutide also had a 36% lower incidence of new or worsening nephropathy (P = .005), and the frequency of serious adverse events was also lower in the semaglutide group than in the placebo patients.
“With the exception of complications of retinopathy, semaglutide had a safety profile similar to that of other GLP-1 receptor agonists,” the authors reported. The rates of malignant neoplasms were similar in both arms of the study, and the rate of pancreatic cancer, which is known to be an event of interest for this class of drugs, was lower in the semaglutide arm, compared with placebo.
Semaglutide is in development and not yet approved for the treatment of type 2 diabetes.
Starting in 2008, all new drug applications to the Food and Drug Administration for antihyperglycemic agents must include evidence that therapy will not increase the risk of cardiovascular events; SUSTAIN-6 (Trial to Evaluate Cardiovascular and Other Long-Term Outcomes With Semaglutide in Subjects with Type 2 Diabetes) was designed to fill that need for semaglutide, and is being developed by Novo Nordisk.
The study was supported by Novo Nordisk. Thirteen authors declared consultancies, grants, fees, and other support from pharmaceutical companies, including Novo Nordisk, and three authors were employees of Novo Nordisk.
AT EASD 2016
Key clinical point: The glucagonlike peptide 1 receptor agonist semaglutide may reduce the risk of cardiovascular events in patients with type 2 diabetes who are at elevated cardiovascular risk.
Major finding: Patients randomized to once-weekly semaglutide had a significant 26% lower risk of first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, compared with those on placebo.
Data source: SUSTAIN-6, a randomized, placebo-controlled noninferiority study.
Disclosures: SUSTAIN-6 was supported by Novo Nordisk. Thirteen authors declared consultancies, grants, fees, and other support from pharmaceutical companies, including Novo Nordisk, and three authors were employees of Novo Nordisk.
Liraglutide cut risk of microvascular renal complications by 22% in type 2 diabetes; no eye benefit
MUNICH – Liraglutide posted positive secondary endpoints in a large randomized trial, reducing the risk of microvascular events by 16% and protecting renal function in people with type 2 diabetes.
A 22% decreased risk of renal complications was the major driver of microvascular protection in the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome) trial, Johannes Mann, MD, said at the annual meeting of the European Association for the Study of Diabetes. Somewhat disappointingly, the glucagonlike peptide–1 (GLP-1) receptor inhibitor didn’t decrease the chance of an eye-related microvascular event, said Dr. Mann of Friedrich Alexander University in Erlangen, Germany.
LEADER randomized 9,340 patients with type 2 diabetes to 1.8 mg or the maximum tolerated dose of subcutaneous liraglutide once daily or to placebo, in addition to standard care (N Engl J Med. 2016 June 13. doi: 10.1056/NEJMoa1603827)
The primary endpoint, reported in June, was a 13% reduction in the risk of a composite cardiovascular outcome (cardiovascular death, nonfatal heart attack, or nonfatal stroke) over 3.8 years of follow-up. This was driven by a 22% reduction in the risk of cardiovascular death; the drug did not significantly impact the other endpoints.
Microvascular and safety endpoints were key secondary outcomes. The study population was already at high risk for renal complications, Dr. Mann said: 20% had a moderate renal impairment at baseline, 20% had microalbuminuria, and 5% had macroalbuminuria.
The renal microvascular endpoint was a composite of several measures: new-onset persistent macroalbuminuria, persistent doubling of serum creatinine, end-stage renal disease, or death from renal failure. It occurred in 7.6% of the liraglutide group and 8.9% of the placebo group. The difference represented a 22% reduction in the time to a first renal event (hazard ratio, 0.78). This was entirely driven by a significant 23% decrease in the chance of new-onset macroalbuminuria (hazard ratio, 0.74), which occurred in 3.4% of the liraglutide group and 4.6% of the placebo group.
There were no significant between-group differences in any of the other renal endpoints, Dr. Mann said.
The eye microvascular endpoint was a composite of vitreous hemorrhage or treatment with photocoagulation or an intravitreal agent. The composite endpoint occurred in 2.3% of the liraglutide group and 2% of the placebo group, which was not a significant difference (HR, 1.15).
The drug was not associated with an increased risk of pancreatitis, with 18 suspected events in the treated group vs. 33 in the placebo group, not a significant difference. None of the cases was time bound; they occurred randomly throughout the trial in both treatment arms, said Michael A. Nauck, MD, of St. Josef Hospital, Bochum, Germany,
But any cases were a cause of concern, Dr. Nauck said, especially since liraglutide, like any GLP-1 agonist, causes increases in the pancreatic enzymes lipase and amylase. Therefore, each suspected case of acute pancreatitis that occurred in either group was fully adjudicated according to three diagnostic criteria: characteristic upper abdominal pain, increased pancreatic enzymes, and imaging findings.
Most of the cases (79% on liraglutide and 58% on placebo) had two of these criteria; the rest fulfilled all three. Any one was enough to prompt a pancreatitis work-up. Pain was the presenting symptom in 40% of liraglutide patients and 74% of placebo patients. Elevated enzymes prompted the work-up in another 40% of liraglutide patients and in 26% of placebo patients. The combination of pain and elevated enzymes was present in 6% of liraglutide patients, and in none of the placebo patients.
But pancreatic imaging was negative in 77% of liraglutide patients and 61% of placebo patients, suggesting that most of the reports did not represent a true acute inflammatory pancreatitis, Dr. Nauck said.
There was no significant liraglutide-associated increase in the risk of any neoplasm, whether malignant (HR, 1.06) or benign (HR, 1.16).
Pancreatic cancer occurred in 13 patients taking liraglutide and 9 taking placebo – not a significant difference. There were numerically fewer cases of prostate cancer and leukemia among those taking the drug, but again, the difference was not statistically significant, and the analysis didn’t control for any confounding factors.
“We are not going to say that liraglutide is in any way protective against these cancers,” Dr. Nauck said.
LEADER was sponsored by Novo Nordisk and the National Institutes of Health. Dr. Nauck is on Novo Nordisk’s advisory panel and speakers board, and receives research funding from the company. Dr Mann is an investigator and consultant for the company.
MUNICH – Liraglutide posted positive secondary endpoints in a large randomized trial, reducing the risk of microvascular events by 16% and protecting renal function in people with type 2 diabetes.
A 22% decreased risk of renal complications was the major driver of microvascular protection in the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome) trial, Johannes Mann, MD, said at the annual meeting of the European Association for the Study of Diabetes. Somewhat disappointingly, the glucagonlike peptide–1 (GLP-1) receptor inhibitor didn’t decrease the chance of an eye-related microvascular event, said Dr. Mann of Friedrich Alexander University in Erlangen, Germany.
LEADER randomized 9,340 patients with type 2 diabetes to 1.8 mg or the maximum tolerated dose of subcutaneous liraglutide once daily or to placebo, in addition to standard care (N Engl J Med. 2016 June 13. doi: 10.1056/NEJMoa1603827)
The primary endpoint, reported in June, was a 13% reduction in the risk of a composite cardiovascular outcome (cardiovascular death, nonfatal heart attack, or nonfatal stroke) over 3.8 years of follow-up. This was driven by a 22% reduction in the risk of cardiovascular death; the drug did not significantly impact the other endpoints.
Microvascular and safety endpoints were key secondary outcomes. The study population was already at high risk for renal complications, Dr. Mann said: 20% had a moderate renal impairment at baseline, 20% had microalbuminuria, and 5% had macroalbuminuria.
The renal microvascular endpoint was a composite of several measures: new-onset persistent macroalbuminuria, persistent doubling of serum creatinine, end-stage renal disease, or death from renal failure. It occurred in 7.6% of the liraglutide group and 8.9% of the placebo group. The difference represented a 22% reduction in the time to a first renal event (hazard ratio, 0.78). This was entirely driven by a significant 23% decrease in the chance of new-onset macroalbuminuria (hazard ratio, 0.74), which occurred in 3.4% of the liraglutide group and 4.6% of the placebo group.
There were no significant between-group differences in any of the other renal endpoints, Dr. Mann said.
The eye microvascular endpoint was a composite of vitreous hemorrhage or treatment with photocoagulation or an intravitreal agent. The composite endpoint occurred in 2.3% of the liraglutide group and 2% of the placebo group, which was not a significant difference (HR, 1.15).
The drug was not associated with an increased risk of pancreatitis, with 18 suspected events in the treated group vs. 33 in the placebo group, not a significant difference. None of the cases was time bound; they occurred randomly throughout the trial in both treatment arms, said Michael A. Nauck, MD, of St. Josef Hospital, Bochum, Germany,
But any cases were a cause of concern, Dr. Nauck said, especially since liraglutide, like any GLP-1 agonist, causes increases in the pancreatic enzymes lipase and amylase. Therefore, each suspected case of acute pancreatitis that occurred in either group was fully adjudicated according to three diagnostic criteria: characteristic upper abdominal pain, increased pancreatic enzymes, and imaging findings.
Most of the cases (79% on liraglutide and 58% on placebo) had two of these criteria; the rest fulfilled all three. Any one was enough to prompt a pancreatitis work-up. Pain was the presenting symptom in 40% of liraglutide patients and 74% of placebo patients. Elevated enzymes prompted the work-up in another 40% of liraglutide patients and in 26% of placebo patients. The combination of pain and elevated enzymes was present in 6% of liraglutide patients, and in none of the placebo patients.
But pancreatic imaging was negative in 77% of liraglutide patients and 61% of placebo patients, suggesting that most of the reports did not represent a true acute inflammatory pancreatitis, Dr. Nauck said.
There was no significant liraglutide-associated increase in the risk of any neoplasm, whether malignant (HR, 1.06) or benign (HR, 1.16).
Pancreatic cancer occurred in 13 patients taking liraglutide and 9 taking placebo – not a significant difference. There were numerically fewer cases of prostate cancer and leukemia among those taking the drug, but again, the difference was not statistically significant, and the analysis didn’t control for any confounding factors.
“We are not going to say that liraglutide is in any way protective against these cancers,” Dr. Nauck said.
LEADER was sponsored by Novo Nordisk and the National Institutes of Health. Dr. Nauck is on Novo Nordisk’s advisory panel and speakers board, and receives research funding from the company. Dr Mann is an investigator and consultant for the company.
MUNICH – Liraglutide posted positive secondary endpoints in a large randomized trial, reducing the risk of microvascular events by 16% and protecting renal function in people with type 2 diabetes.
A 22% decreased risk of renal complications was the major driver of microvascular protection in the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome) trial, Johannes Mann, MD, said at the annual meeting of the European Association for the Study of Diabetes. Somewhat disappointingly, the glucagonlike peptide–1 (GLP-1) receptor inhibitor didn’t decrease the chance of an eye-related microvascular event, said Dr. Mann of Friedrich Alexander University in Erlangen, Germany.
LEADER randomized 9,340 patients with type 2 diabetes to 1.8 mg or the maximum tolerated dose of subcutaneous liraglutide once daily or to placebo, in addition to standard care (N Engl J Med. 2016 June 13. doi: 10.1056/NEJMoa1603827)
The primary endpoint, reported in June, was a 13% reduction in the risk of a composite cardiovascular outcome (cardiovascular death, nonfatal heart attack, or nonfatal stroke) over 3.8 years of follow-up. This was driven by a 22% reduction in the risk of cardiovascular death; the drug did not significantly impact the other endpoints.
Microvascular and safety endpoints were key secondary outcomes. The study population was already at high risk for renal complications, Dr. Mann said: 20% had a moderate renal impairment at baseline, 20% had microalbuminuria, and 5% had macroalbuminuria.
The renal microvascular endpoint was a composite of several measures: new-onset persistent macroalbuminuria, persistent doubling of serum creatinine, end-stage renal disease, or death from renal failure. It occurred in 7.6% of the liraglutide group and 8.9% of the placebo group. The difference represented a 22% reduction in the time to a first renal event (hazard ratio, 0.78). This was entirely driven by a significant 23% decrease in the chance of new-onset macroalbuminuria (hazard ratio, 0.74), which occurred in 3.4% of the liraglutide group and 4.6% of the placebo group.
There were no significant between-group differences in any of the other renal endpoints, Dr. Mann said.
The eye microvascular endpoint was a composite of vitreous hemorrhage or treatment with photocoagulation or an intravitreal agent. The composite endpoint occurred in 2.3% of the liraglutide group and 2% of the placebo group, which was not a significant difference (HR, 1.15).
The drug was not associated with an increased risk of pancreatitis, with 18 suspected events in the treated group vs. 33 in the placebo group, not a significant difference. None of the cases was time bound; they occurred randomly throughout the trial in both treatment arms, said Michael A. Nauck, MD, of St. Josef Hospital, Bochum, Germany,
But any cases were a cause of concern, Dr. Nauck said, especially since liraglutide, like any GLP-1 agonist, causes increases in the pancreatic enzymes lipase and amylase. Therefore, each suspected case of acute pancreatitis that occurred in either group was fully adjudicated according to three diagnostic criteria: characteristic upper abdominal pain, increased pancreatic enzymes, and imaging findings.
Most of the cases (79% on liraglutide and 58% on placebo) had two of these criteria; the rest fulfilled all three. Any one was enough to prompt a pancreatitis work-up. Pain was the presenting symptom in 40% of liraglutide patients and 74% of placebo patients. Elevated enzymes prompted the work-up in another 40% of liraglutide patients and in 26% of placebo patients. The combination of pain and elevated enzymes was present in 6% of liraglutide patients, and in none of the placebo patients.
But pancreatic imaging was negative in 77% of liraglutide patients and 61% of placebo patients, suggesting that most of the reports did not represent a true acute inflammatory pancreatitis, Dr. Nauck said.
There was no significant liraglutide-associated increase in the risk of any neoplasm, whether malignant (HR, 1.06) or benign (HR, 1.16).
Pancreatic cancer occurred in 13 patients taking liraglutide and 9 taking placebo – not a significant difference. There were numerically fewer cases of prostate cancer and leukemia among those taking the drug, but again, the difference was not statistically significant, and the analysis didn’t control for any confounding factors.
“We are not going to say that liraglutide is in any way protective against these cancers,” Dr. Nauck said.
LEADER was sponsored by Novo Nordisk and the National Institutes of Health. Dr. Nauck is on Novo Nordisk’s advisory panel and speakers board, and receives research funding from the company. Dr Mann is an investigator and consultant for the company.
AT EASD 2016
Key clinical point: Liraglutide protected kidney function but conferred no benefit on microvascular eye complications in patients with type 2 diabetes.
Major finding: The benefit was driven by a 24% decreased risk of macroalbuminuria.
Data source: The LEADER trial randomized 9,340 patients with type 2 diabetes to daily 1.8 mg liraglutide or placebo, in addition to standard care.
Disclosures: LEADER was sponsored by Novo Nordisk and the National Institutes of Health. Dr. Nauck is on Novo Nordisk’s advisory panel and speakers board, and receives research funding from the company. Dr Mann is an investigator and consultant for the company.
Exenatide/dapagliflozin combo may be better in stubborn diabetes
The combination of exenatide and dapagliflozin produced better results than did either drug alone in patients with type 2 diabetes whose glucose levels aren’t controlled effectively by metformin.
At 28 weeks, HbA1c levels were lower in the combination group, where a third of patients lost more than 5% of their body weight, and 45% reached HbA1c levels under 7.0%, outpacing those on the solo treatments.
Cristian Guja, MD, of the Carol Davila University of Medicine and Pharmacy in Bucharest, Romania, presented the findings of DURATION-8, a 28-week randomized, double-blinded study at 109 sites in six countries, Sept. 16 at the annual meeting of the European Association for the Study of Diabetes. The study was published simultaneously in the Lancet Diabetes & Endocrinology.
In 2014 and 2015, 695 adults with type 2 diabetes and insufficient glycemic control, defined as HbA1c 8%-12%, were randomly assigned to one of three groups: exenatide plus dapagliflozin (n = 231), exenatide alone (n = 231; n = 1 untreated), or dapagliflozin alone (n = 233). All were given placebo pills or injections for 1 week before randomization.
Patients’ average age was 54-55 years, most were white (82%-85%), with 37%-42% reporting Hispanic heritage. Men and women were nearly equally represented. The average body mass index was 32-33 kg/m2. Patients took basal insulin on a rescue basis as needed and were continued on prescribed blood pressure and cholesterol medications.
At 28 weeks, baseline HbA1c in the combination group fell by 2.0% (9.3% to 7.3%), compared with 1.6% (9.3% to 7.6%) in the exenatide-only group and by 1.4% (9.3% to 7.8%) in the dapagliflozin-only group.
Combination therapy was “significantly superior” to either drug alone for all secondary endpoints, including reduced fasting plasma and postprandial glucose, more patients with an HbA1c less than 7.0%, weight-related measures, and lowered systolic blood pressure (Lancet Diabetes Endocrinol. 2016 Sep 16. doi. org/10.1016/S2213-8587(16)30267-4).
Specifically, the percentage of patients with an HbA1c less than 7.0% was 45% for the combination group, 27% for the exenatide group, and 19% for the dapagliflozin group at 28 weeks. A third of patients taking the combination lost more than 5% of their weight, compared with 14% of those on exenatide alone and 20% of those on dapagliflozin.
The side-effect rate (57%) was highest in the combination group and lower (54% and 52%, respectively) for the exenatide and dapagliflozin groups.
Diarrhea, injection-site nodules, nausea, and urinary tract infection occurred in 5% or more of patients in at least one of the three groups. Across all study groups, 2%-5% of patients discontinued treatment because of side effects; discontinuation was greatest (5%) in the exenatide group. Three patients in the combination group died, as did one patient in each of the solo-treatment groups.
This study “provides high-quality evidence that the combination of exenatide and dapagliflozin is more effective than either drug alone in patients with inadequate response to metformin monotherapy,” Dr. Guja and his colleagues noted.
In a commentary, Michael A. Nauck, MD, and Juris J. Meier, MD, both of St. Josef Hospital in Bochum, Germany, called the percentage of patients (45%) who reached an HbA1c level of less than 7.0% in the combination treatment group “disappointing.” They suggested that GLP-1 receptor agonists (i.e., exenatide) may be more effective when combined with SGLT2 inhibitors (i.e., dapagliflozin) than when used with insulin treatment.
The study was funded by AstraZeneca, maker of both exenatide and dapagliflozin.
The combination of exenatide and dapagliflozin produced better results than did either drug alone in patients with type 2 diabetes whose glucose levels aren’t controlled effectively by metformin.
At 28 weeks, HbA1c levels were lower in the combination group, where a third of patients lost more than 5% of their body weight, and 45% reached HbA1c levels under 7.0%, outpacing those on the solo treatments.
Cristian Guja, MD, of the Carol Davila University of Medicine and Pharmacy in Bucharest, Romania, presented the findings of DURATION-8, a 28-week randomized, double-blinded study at 109 sites in six countries, Sept. 16 at the annual meeting of the European Association for the Study of Diabetes. The study was published simultaneously in the Lancet Diabetes & Endocrinology.
In 2014 and 2015, 695 adults with type 2 diabetes and insufficient glycemic control, defined as HbA1c 8%-12%, were randomly assigned to one of three groups: exenatide plus dapagliflozin (n = 231), exenatide alone (n = 231; n = 1 untreated), or dapagliflozin alone (n = 233). All were given placebo pills or injections for 1 week before randomization.
Patients’ average age was 54-55 years, most were white (82%-85%), with 37%-42% reporting Hispanic heritage. Men and women were nearly equally represented. The average body mass index was 32-33 kg/m2. Patients took basal insulin on a rescue basis as needed and were continued on prescribed blood pressure and cholesterol medications.
At 28 weeks, baseline HbA1c in the combination group fell by 2.0% (9.3% to 7.3%), compared with 1.6% (9.3% to 7.6%) in the exenatide-only group and by 1.4% (9.3% to 7.8%) in the dapagliflozin-only group.
Combination therapy was “significantly superior” to either drug alone for all secondary endpoints, including reduced fasting plasma and postprandial glucose, more patients with an HbA1c less than 7.0%, weight-related measures, and lowered systolic blood pressure (Lancet Diabetes Endocrinol. 2016 Sep 16. doi. org/10.1016/S2213-8587(16)30267-4).
Specifically, the percentage of patients with an HbA1c less than 7.0% was 45% for the combination group, 27% for the exenatide group, and 19% for the dapagliflozin group at 28 weeks. A third of patients taking the combination lost more than 5% of their weight, compared with 14% of those on exenatide alone and 20% of those on dapagliflozin.
The side-effect rate (57%) was highest in the combination group and lower (54% and 52%, respectively) for the exenatide and dapagliflozin groups.
Diarrhea, injection-site nodules, nausea, and urinary tract infection occurred in 5% or more of patients in at least one of the three groups. Across all study groups, 2%-5% of patients discontinued treatment because of side effects; discontinuation was greatest (5%) in the exenatide group. Three patients in the combination group died, as did one patient in each of the solo-treatment groups.
This study “provides high-quality evidence that the combination of exenatide and dapagliflozin is more effective than either drug alone in patients with inadequate response to metformin monotherapy,” Dr. Guja and his colleagues noted.
In a commentary, Michael A. Nauck, MD, and Juris J. Meier, MD, both of St. Josef Hospital in Bochum, Germany, called the percentage of patients (45%) who reached an HbA1c level of less than 7.0% in the combination treatment group “disappointing.” They suggested that GLP-1 receptor agonists (i.e., exenatide) may be more effective when combined with SGLT2 inhibitors (i.e., dapagliflozin) than when used with insulin treatment.
The study was funded by AstraZeneca, maker of both exenatide and dapagliflozin.
The combination of exenatide and dapagliflozin produced better results than did either drug alone in patients with type 2 diabetes whose glucose levels aren’t controlled effectively by metformin.
At 28 weeks, HbA1c levels were lower in the combination group, where a third of patients lost more than 5% of their body weight, and 45% reached HbA1c levels under 7.0%, outpacing those on the solo treatments.
Cristian Guja, MD, of the Carol Davila University of Medicine and Pharmacy in Bucharest, Romania, presented the findings of DURATION-8, a 28-week randomized, double-blinded study at 109 sites in six countries, Sept. 16 at the annual meeting of the European Association for the Study of Diabetes. The study was published simultaneously in the Lancet Diabetes & Endocrinology.
In 2014 and 2015, 695 adults with type 2 diabetes and insufficient glycemic control, defined as HbA1c 8%-12%, were randomly assigned to one of three groups: exenatide plus dapagliflozin (n = 231), exenatide alone (n = 231; n = 1 untreated), or dapagliflozin alone (n = 233). All were given placebo pills or injections for 1 week before randomization.
Patients’ average age was 54-55 years, most were white (82%-85%), with 37%-42% reporting Hispanic heritage. Men and women were nearly equally represented. The average body mass index was 32-33 kg/m2. Patients took basal insulin on a rescue basis as needed and were continued on prescribed blood pressure and cholesterol medications.
At 28 weeks, baseline HbA1c in the combination group fell by 2.0% (9.3% to 7.3%), compared with 1.6% (9.3% to 7.6%) in the exenatide-only group and by 1.4% (9.3% to 7.8%) in the dapagliflozin-only group.
Combination therapy was “significantly superior” to either drug alone for all secondary endpoints, including reduced fasting plasma and postprandial glucose, more patients with an HbA1c less than 7.0%, weight-related measures, and lowered systolic blood pressure (Lancet Diabetes Endocrinol. 2016 Sep 16. doi. org/10.1016/S2213-8587(16)30267-4).
Specifically, the percentage of patients with an HbA1c less than 7.0% was 45% for the combination group, 27% for the exenatide group, and 19% for the dapagliflozin group at 28 weeks. A third of patients taking the combination lost more than 5% of their weight, compared with 14% of those on exenatide alone and 20% of those on dapagliflozin.
The side-effect rate (57%) was highest in the combination group and lower (54% and 52%, respectively) for the exenatide and dapagliflozin groups.
Diarrhea, injection-site nodules, nausea, and urinary tract infection occurred in 5% or more of patients in at least one of the three groups. Across all study groups, 2%-5% of patients discontinued treatment because of side effects; discontinuation was greatest (5%) in the exenatide group. Three patients in the combination group died, as did one patient in each of the solo-treatment groups.
This study “provides high-quality evidence that the combination of exenatide and dapagliflozin is more effective than either drug alone in patients with inadequate response to metformin monotherapy,” Dr. Guja and his colleagues noted.
In a commentary, Michael A. Nauck, MD, and Juris J. Meier, MD, both of St. Josef Hospital in Bochum, Germany, called the percentage of patients (45%) who reached an HbA1c level of less than 7.0% in the combination treatment group “disappointing.” They suggested that GLP-1 receptor agonists (i.e., exenatide) may be more effective when combined with SGLT2 inhibitors (i.e., dapagliflozin) than when used with insulin treatment.
The study was funded by AstraZeneca, maker of both exenatide and dapagliflozin.
FROM EASD 2016
Key clinical point: An exenatide-dapagliflozin combination may be better than either drug alone for patients with type 2 diabetes who have not responded to metformin.
Major finding: At 28 weeks, baseline HbA1c was reduced by 2.0% to 7.3% in the combination group, compared with 1.6% to 7.6% in the exenatide-only group and by 1.4% to 7.8% in the dapagliflozin-only group.
Data source: Double-blind, randomized, active-controlled phase III trial of 685 patients (611 completed) over 28 weeks.
Disclosures: The study was funded by AstraZeneca. Study authors reported grants and similar funding from many pharmaceutical companies including AstraZeneca.
Dulaglutide plus insulin glargine drops HbA1c in poorly controlled type 2
MUNICH – Once-weekly dulaglutide paired with insulin glargine plus metformin allowed 69% of patients with poorly controlled type 2 diabetes to achieve a hemoglobin A1c of 7% or lower.
Over the 28-week study, 51% of the group reached an HbA1c of 6.5% or lower – significantly better than the 17% who achieved this goal on insulin glargine with or without metformin, Paolo Pozzilli, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
The combination was safe, with just one incident of severe hypoglycemia, and well tolerated, said Dr. Pozzilli of the University Campus Bio-Medico, Rome. Nausea – the most troublesome side effect of any glucagonlike peptide receptor agonist occurred in 12% of those taking the drug. Diarrhea occurred in 11% and vomiting in 6%. All of the gastrointestinal side effects were significantly more common than they were in the placebo group.
“I would say that the combination treatment of dulaglutide and insulin glargine – with or without metformin – is a reasonable, well-tolerated, and effective option for patients with type 2 diabetes who are not hitting their treatment goals,” he said.
Dr. Pozzilli reported results of Lily’s AWARD-9 trial. The placebo-controlled trial comprised 300 patients with poorly controlled type 2 diabetes (HbA1c, 7%-10.5%), despite being on insulin glargine and metformin. They were randomized to weekly subcutaneous placebo or 1.5 mg dulaglutide injections, in addition to their usual medications. There was no up titration on the study drug – patients started out with the full dose immediately. The study’s completion rate was high, with 92% of the investigational group and 87% of the control group finishing the 28-week treatment.
The group was typical for poorly controlled type 2 patients. Their mean age was 60 years; about 60% were men; and almost all were white. The mean body mass index was 32 kg/m2. The mean disease duration was 13 years, and the mean HbA1c was 8.4%. Their mean fasting plasma glucose was 8.7 mmol/L.
The effect of dual therapy was quickly evident, with HbA1c levels beginning to drop within 2 weeks. By 12 weeks, the separation between groups was statistically significant (dulaglutide HbA1c about 7%, placebo about 8%). By 28 weeks, the combination group had reached a mean HbA1c of 6.92%, compared with 7.69% in the placebo group. The response curve of the combination group appeared to be on a continuing decline when the study ended. The final measure represented an HbA1c decrease of 1.44% for the combination group and 0.67% for the placebo group.
By 28 weeks, 69% of the dulaglutide group and 35% of the placebo group had achieved an HbA1c of 7% or lower – a significant difference. Half of the dulaglutide group (51%) achieved a measure of 6.5% or lower, compared with 17% of the placebo group – also a significant difference.
The addition of dulaglutide moderated the need to increase the insulin that occurred over the study period. By 28 weeks, those taking dulaglutide had increased their insulin by a mean of 0.14 U/kg, compared with an increase of 0.27 U/kg in the placebo group. This difference was also statistically significant.
Patients in the combination group lost significantly more weight as well (mean 1.91 kg vs. a gain of 0.5 kg in the placebo group). Weight loss was quickly evident; by 4 weeks, patients had lost more than 1 kg. This “encouraging sign might help boost patient compliance,” Dr. Pozzilli said.
The side-effect profile was acceptable, compared with placebo. Hypoglycemia occurred in about 55% of those taking dulaglutide and 51% of those taking the placebo; it was symptomatic in 35% and 30%, respectively. Nocturnal hypoglycemia occurred in 28% and 29%, respectively. There was one case of severe hypoglycemia, which occurred in the dulaglutide group.
In addition to the GI side effects, there was one injection site reaction in the dulaglutide group. There were no cases of pancreatitis or pancreatic cancer.
The study was sponsored by Eli Lilly. Dr. Pozzilli is on the company’s speakers’ bureau and receives research grant money from it.
MUNICH – Once-weekly dulaglutide paired with insulin glargine plus metformin allowed 69% of patients with poorly controlled type 2 diabetes to achieve a hemoglobin A1c of 7% or lower.
Over the 28-week study, 51% of the group reached an HbA1c of 6.5% or lower – significantly better than the 17% who achieved this goal on insulin glargine with or without metformin, Paolo Pozzilli, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
The combination was safe, with just one incident of severe hypoglycemia, and well tolerated, said Dr. Pozzilli of the University Campus Bio-Medico, Rome. Nausea – the most troublesome side effect of any glucagonlike peptide receptor agonist occurred in 12% of those taking the drug. Diarrhea occurred in 11% and vomiting in 6%. All of the gastrointestinal side effects were significantly more common than they were in the placebo group.
“I would say that the combination treatment of dulaglutide and insulin glargine – with or without metformin – is a reasonable, well-tolerated, and effective option for patients with type 2 diabetes who are not hitting their treatment goals,” he said.
Dr. Pozzilli reported results of Lily’s AWARD-9 trial. The placebo-controlled trial comprised 300 patients with poorly controlled type 2 diabetes (HbA1c, 7%-10.5%), despite being on insulin glargine and metformin. They were randomized to weekly subcutaneous placebo or 1.5 mg dulaglutide injections, in addition to their usual medications. There was no up titration on the study drug – patients started out with the full dose immediately. The study’s completion rate was high, with 92% of the investigational group and 87% of the control group finishing the 28-week treatment.
The group was typical for poorly controlled type 2 patients. Their mean age was 60 years; about 60% were men; and almost all were white. The mean body mass index was 32 kg/m2. The mean disease duration was 13 years, and the mean HbA1c was 8.4%. Their mean fasting plasma glucose was 8.7 mmol/L.
The effect of dual therapy was quickly evident, with HbA1c levels beginning to drop within 2 weeks. By 12 weeks, the separation between groups was statistically significant (dulaglutide HbA1c about 7%, placebo about 8%). By 28 weeks, the combination group had reached a mean HbA1c of 6.92%, compared with 7.69% in the placebo group. The response curve of the combination group appeared to be on a continuing decline when the study ended. The final measure represented an HbA1c decrease of 1.44% for the combination group and 0.67% for the placebo group.
By 28 weeks, 69% of the dulaglutide group and 35% of the placebo group had achieved an HbA1c of 7% or lower – a significant difference. Half of the dulaglutide group (51%) achieved a measure of 6.5% or lower, compared with 17% of the placebo group – also a significant difference.
The addition of dulaglutide moderated the need to increase the insulin that occurred over the study period. By 28 weeks, those taking dulaglutide had increased their insulin by a mean of 0.14 U/kg, compared with an increase of 0.27 U/kg in the placebo group. This difference was also statistically significant.
Patients in the combination group lost significantly more weight as well (mean 1.91 kg vs. a gain of 0.5 kg in the placebo group). Weight loss was quickly evident; by 4 weeks, patients had lost more than 1 kg. This “encouraging sign might help boost patient compliance,” Dr. Pozzilli said.
The side-effect profile was acceptable, compared with placebo. Hypoglycemia occurred in about 55% of those taking dulaglutide and 51% of those taking the placebo; it was symptomatic in 35% and 30%, respectively. Nocturnal hypoglycemia occurred in 28% and 29%, respectively. There was one case of severe hypoglycemia, which occurred in the dulaglutide group.
In addition to the GI side effects, there was one injection site reaction in the dulaglutide group. There were no cases of pancreatitis or pancreatic cancer.
The study was sponsored by Eli Lilly. Dr. Pozzilli is on the company’s speakers’ bureau and receives research grant money from it.
MUNICH – Once-weekly dulaglutide paired with insulin glargine plus metformin allowed 69% of patients with poorly controlled type 2 diabetes to achieve a hemoglobin A1c of 7% or lower.
Over the 28-week study, 51% of the group reached an HbA1c of 6.5% or lower – significantly better than the 17% who achieved this goal on insulin glargine with or without metformin, Paolo Pozzilli, MD, reported at the annual meeting of the European Association for the Study of Diabetes.
The combination was safe, with just one incident of severe hypoglycemia, and well tolerated, said Dr. Pozzilli of the University Campus Bio-Medico, Rome. Nausea – the most troublesome side effect of any glucagonlike peptide receptor agonist occurred in 12% of those taking the drug. Diarrhea occurred in 11% and vomiting in 6%. All of the gastrointestinal side effects were significantly more common than they were in the placebo group.
“I would say that the combination treatment of dulaglutide and insulin glargine – with or without metformin – is a reasonable, well-tolerated, and effective option for patients with type 2 diabetes who are not hitting their treatment goals,” he said.
Dr. Pozzilli reported results of Lily’s AWARD-9 trial. The placebo-controlled trial comprised 300 patients with poorly controlled type 2 diabetes (HbA1c, 7%-10.5%), despite being on insulin glargine and metformin. They were randomized to weekly subcutaneous placebo or 1.5 mg dulaglutide injections, in addition to their usual medications. There was no up titration on the study drug – patients started out with the full dose immediately. The study’s completion rate was high, with 92% of the investigational group and 87% of the control group finishing the 28-week treatment.
The group was typical for poorly controlled type 2 patients. Their mean age was 60 years; about 60% were men; and almost all were white. The mean body mass index was 32 kg/m2. The mean disease duration was 13 years, and the mean HbA1c was 8.4%. Their mean fasting plasma glucose was 8.7 mmol/L.
The effect of dual therapy was quickly evident, with HbA1c levels beginning to drop within 2 weeks. By 12 weeks, the separation between groups was statistically significant (dulaglutide HbA1c about 7%, placebo about 8%). By 28 weeks, the combination group had reached a mean HbA1c of 6.92%, compared with 7.69% in the placebo group. The response curve of the combination group appeared to be on a continuing decline when the study ended. The final measure represented an HbA1c decrease of 1.44% for the combination group and 0.67% for the placebo group.
By 28 weeks, 69% of the dulaglutide group and 35% of the placebo group had achieved an HbA1c of 7% or lower – a significant difference. Half of the dulaglutide group (51%) achieved a measure of 6.5% or lower, compared with 17% of the placebo group – also a significant difference.
The addition of dulaglutide moderated the need to increase the insulin that occurred over the study period. By 28 weeks, those taking dulaglutide had increased their insulin by a mean of 0.14 U/kg, compared with an increase of 0.27 U/kg in the placebo group. This difference was also statistically significant.
Patients in the combination group lost significantly more weight as well (mean 1.91 kg vs. a gain of 0.5 kg in the placebo group). Weight loss was quickly evident; by 4 weeks, patients had lost more than 1 kg. This “encouraging sign might help boost patient compliance,” Dr. Pozzilli said.
The side-effect profile was acceptable, compared with placebo. Hypoglycemia occurred in about 55% of those taking dulaglutide and 51% of those taking the placebo; it was symptomatic in 35% and 30%, respectively. Nocturnal hypoglycemia occurred in 28% and 29%, respectively. There was one case of severe hypoglycemia, which occurred in the dulaglutide group.
In addition to the GI side effects, there was one injection site reaction in the dulaglutide group. There were no cases of pancreatitis or pancreatic cancer.
The study was sponsored by Eli Lilly. Dr. Pozzilli is on the company’s speakers’ bureau and receives research grant money from it.
AT EASD 2016
Key clinical point: Adding dulaglutide to insulin glargine and metformin significantly improved long-term blood glucose levels.
Major finding: The combination of dulaglutide plus insulin glargine and metformin took 69% of patients to an HbA1c of 7% or lower.
Data source: The randomized, placebo-controlled AWARD-9 study comprised 300 patients with poorly controlled type 2 diabetes.
Disclosures: Eli Lilly sponsored the trials. Dr. Pozzilli is on the company’s speaker’s bureau and receives research funding from it.
Insulin-dependent pilots can fly safely with glucose monitoring protocol
MUNICH – British commercial pilots with insulin-dependent diabetes are flying safely, thanks to a rigorous protocol of hourly blood glucose monitoring during every flight.
Almost every one of the 8,897 readings reported so far has been in the safe “green zone” of 5-15 mmol/L, Julia Hine, MD, said at the annual meeting of the European Association for the Study of Diabetes.
Only 3.8% fell in the cautionary “amber” range of 4-5 mmol/L or 15-19 mmol/L. Just 0.2% (22) were in the “red” range of below 4 mmol/L or above 20 mmol/L – an occurrence that demands immediate release of airplane control to the copilot.
Reassuringly, only five of those readings occurred during flight, said Dr. Hine of the Royal Surrey County Hospital, England. The rest were taken during the preflight preparation period.
She said the 4-year data confirm that the protocol works, allowing highly skilled professionals to return to their work without compromising personal safety or the safety of those entrusted to their care.
“The testing protocol can be performed safely in the cockpit, with no safety concerns,” Dr. Hine said. “It represents an advance in patient care, showing that insulin-dependent patients can perform complex occupational duties.”
The protocol was instituted in 2012, after a consortium of commercial pilots met with diabetes specialists to create a way for certified pilots to regain their class 1 licenses after a diabetes diagnosis. It’s overseen by the U.K. Civil Aviation Authority and Irish Aviation Authority. Dr. Hine said the U.K. has the largest cadre of certified pilots who have insulin-dependent diabetes in the world. Canada is the only other country with such a program, although, she said, “There are a number of European states that have expressed interest in the program.”
In the United States, a diagnosis of insulin-dependent diabetes currently excludes pilots from flying commercial aircraft. The American Diabetes Association has been lobbying for easing of this strict FAA ban since at least 2014, stating that “the FAA’s blanket ban is not medically justified.” Specifically, the ADA favors a position in which “individual assessment of people with diabetes is the appropriate approach to determining whether a person is qualified to perform certain activities,” according to a statement.
The British protocol requires stringent pre- and in-flight blood sugar monitoring. Levels must be obtained at least 1 hour before reporting for duty and at least 2 hours before commencing a flight.
Blood sugar must be regularly measured during flight at well. For pilots using insulin, levels should be drawn every 2 hours, and for those on oral medications, every 2-4 hours. A final level must be drawn 30 minutes before landing.
Additional testing is required if the pilot experiences any symptoms related to fluctuating blood sugar. All results are read out loud, reported to the copilot and into the plane’s voice data recorder, and recorded in the pilot’s flight data record.
Levels in the amber range require the pilot to take corrective action. For low blood glucose levels, the pilot must consume 10-15 grams of carbohydrate, retest after 30 minutes, and adjust insulin. For high blood glucose levels, the pilot should review insulin dosing and modify carbohydrate intake, then retest in 45 minutes.
Readings in the red range demand immediate action, which includes handing over control of the flight, repeat testing, modifying insulin and carbohydrate intake, and retesting. The pilot may only resume duty when blood glucose returns to a green level.
There is a special protocol for pilots on insulin pumps, which are not guaranteed to function if there is a sudden loss of cabin pressure.
Dr. Hine and her colleague David Russell-Jones, MD, who is the program’s medical director, presented 4 years’ worth of data on 16 of the 26 pilots who have participated in the program. All of these pilots are otherwise healthy men with well-controlled diabetes who were deemed at low risk for glycemic events. They are an average of 40 years old with an average disease duration of 8 years. Their average HbA1c was 53 mmol/l before licensure and 54.8 mmol/l afterwards. All of the pilots have normal renal function, no retinopathy, no changes in blood pressure, and good awareness of hypoglycemia.
Among them, they have accumulated 4,900 flight hours and 8,897 blood glucose readings. Most of the flights (88%) were medium- or short-haul flights of less than 6 hours.
Even though 96% of readings fell into the 5-20 mmol/l green range, the bulk of those readings were in the range of 5-9 mmol/l. There was very little hourly variation in blood glucose levels during flights up to 6 hours, showing that the protocol is effective at establishing stable glycemia.
Right now, the program is in place only for current pilots who have a new diagnosis of diabetes. But, said Dr. Russell-Jones, it may be expanded at some point to encompass people with diabetes who wish to train to become a commercial pilot.
Neither Dr. Hines nor Dr. Russell-Jones reported any financial conflicts.
On Twitter @Alz_Gal
MUNICH – British commercial pilots with insulin-dependent diabetes are flying safely, thanks to a rigorous protocol of hourly blood glucose monitoring during every flight.
Almost every one of the 8,897 readings reported so far has been in the safe “green zone” of 5-15 mmol/L, Julia Hine, MD, said at the annual meeting of the European Association for the Study of Diabetes.
Only 3.8% fell in the cautionary “amber” range of 4-5 mmol/L or 15-19 mmol/L. Just 0.2% (22) were in the “red” range of below 4 mmol/L or above 20 mmol/L – an occurrence that demands immediate release of airplane control to the copilot.
Reassuringly, only five of those readings occurred during flight, said Dr. Hine of the Royal Surrey County Hospital, England. The rest were taken during the preflight preparation period.
She said the 4-year data confirm that the protocol works, allowing highly skilled professionals to return to their work without compromising personal safety or the safety of those entrusted to their care.
“The testing protocol can be performed safely in the cockpit, with no safety concerns,” Dr. Hine said. “It represents an advance in patient care, showing that insulin-dependent patients can perform complex occupational duties.”
The protocol was instituted in 2012, after a consortium of commercial pilots met with diabetes specialists to create a way for certified pilots to regain their class 1 licenses after a diabetes diagnosis. It’s overseen by the U.K. Civil Aviation Authority and Irish Aviation Authority. Dr. Hine said the U.K. has the largest cadre of certified pilots who have insulin-dependent diabetes in the world. Canada is the only other country with such a program, although, she said, “There are a number of European states that have expressed interest in the program.”
In the United States, a diagnosis of insulin-dependent diabetes currently excludes pilots from flying commercial aircraft. The American Diabetes Association has been lobbying for easing of this strict FAA ban since at least 2014, stating that “the FAA’s blanket ban is not medically justified.” Specifically, the ADA favors a position in which “individual assessment of people with diabetes is the appropriate approach to determining whether a person is qualified to perform certain activities,” according to a statement.
The British protocol requires stringent pre- and in-flight blood sugar monitoring. Levels must be obtained at least 1 hour before reporting for duty and at least 2 hours before commencing a flight.
Blood sugar must be regularly measured during flight at well. For pilots using insulin, levels should be drawn every 2 hours, and for those on oral medications, every 2-4 hours. A final level must be drawn 30 minutes before landing.
Additional testing is required if the pilot experiences any symptoms related to fluctuating blood sugar. All results are read out loud, reported to the copilot and into the plane’s voice data recorder, and recorded in the pilot’s flight data record.
Levels in the amber range require the pilot to take corrective action. For low blood glucose levels, the pilot must consume 10-15 grams of carbohydrate, retest after 30 minutes, and adjust insulin. For high blood glucose levels, the pilot should review insulin dosing and modify carbohydrate intake, then retest in 45 minutes.
Readings in the red range demand immediate action, which includes handing over control of the flight, repeat testing, modifying insulin and carbohydrate intake, and retesting. The pilot may only resume duty when blood glucose returns to a green level.
There is a special protocol for pilots on insulin pumps, which are not guaranteed to function if there is a sudden loss of cabin pressure.
Dr. Hine and her colleague David Russell-Jones, MD, who is the program’s medical director, presented 4 years’ worth of data on 16 of the 26 pilots who have participated in the program. All of these pilots are otherwise healthy men with well-controlled diabetes who were deemed at low risk for glycemic events. They are an average of 40 years old with an average disease duration of 8 years. Their average HbA1c was 53 mmol/l before licensure and 54.8 mmol/l afterwards. All of the pilots have normal renal function, no retinopathy, no changes in blood pressure, and good awareness of hypoglycemia.
Among them, they have accumulated 4,900 flight hours and 8,897 blood glucose readings. Most of the flights (88%) were medium- or short-haul flights of less than 6 hours.
Even though 96% of readings fell into the 5-20 mmol/l green range, the bulk of those readings were in the range of 5-9 mmol/l. There was very little hourly variation in blood glucose levels during flights up to 6 hours, showing that the protocol is effective at establishing stable glycemia.
Right now, the program is in place only for current pilots who have a new diagnosis of diabetes. But, said Dr. Russell-Jones, it may be expanded at some point to encompass people with diabetes who wish to train to become a commercial pilot.
Neither Dr. Hines nor Dr. Russell-Jones reported any financial conflicts.
On Twitter @Alz_Gal
MUNICH – British commercial pilots with insulin-dependent diabetes are flying safely, thanks to a rigorous protocol of hourly blood glucose monitoring during every flight.
Almost every one of the 8,897 readings reported so far has been in the safe “green zone” of 5-15 mmol/L, Julia Hine, MD, said at the annual meeting of the European Association for the Study of Diabetes.
Only 3.8% fell in the cautionary “amber” range of 4-5 mmol/L or 15-19 mmol/L. Just 0.2% (22) were in the “red” range of below 4 mmol/L or above 20 mmol/L – an occurrence that demands immediate release of airplane control to the copilot.
Reassuringly, only five of those readings occurred during flight, said Dr. Hine of the Royal Surrey County Hospital, England. The rest were taken during the preflight preparation period.
She said the 4-year data confirm that the protocol works, allowing highly skilled professionals to return to their work without compromising personal safety or the safety of those entrusted to their care.
“The testing protocol can be performed safely in the cockpit, with no safety concerns,” Dr. Hine said. “It represents an advance in patient care, showing that insulin-dependent patients can perform complex occupational duties.”
The protocol was instituted in 2012, after a consortium of commercial pilots met with diabetes specialists to create a way for certified pilots to regain their class 1 licenses after a diabetes diagnosis. It’s overseen by the U.K. Civil Aviation Authority and Irish Aviation Authority. Dr. Hine said the U.K. has the largest cadre of certified pilots who have insulin-dependent diabetes in the world. Canada is the only other country with such a program, although, she said, “There are a number of European states that have expressed interest in the program.”
In the United States, a diagnosis of insulin-dependent diabetes currently excludes pilots from flying commercial aircraft. The American Diabetes Association has been lobbying for easing of this strict FAA ban since at least 2014, stating that “the FAA’s blanket ban is not medically justified.” Specifically, the ADA favors a position in which “individual assessment of people with diabetes is the appropriate approach to determining whether a person is qualified to perform certain activities,” according to a statement.
The British protocol requires stringent pre- and in-flight blood sugar monitoring. Levels must be obtained at least 1 hour before reporting for duty and at least 2 hours before commencing a flight.
Blood sugar must be regularly measured during flight at well. For pilots using insulin, levels should be drawn every 2 hours, and for those on oral medications, every 2-4 hours. A final level must be drawn 30 minutes before landing.
Additional testing is required if the pilot experiences any symptoms related to fluctuating blood sugar. All results are read out loud, reported to the copilot and into the plane’s voice data recorder, and recorded in the pilot’s flight data record.
Levels in the amber range require the pilot to take corrective action. For low blood glucose levels, the pilot must consume 10-15 grams of carbohydrate, retest after 30 minutes, and adjust insulin. For high blood glucose levels, the pilot should review insulin dosing and modify carbohydrate intake, then retest in 45 minutes.
Readings in the red range demand immediate action, which includes handing over control of the flight, repeat testing, modifying insulin and carbohydrate intake, and retesting. The pilot may only resume duty when blood glucose returns to a green level.
There is a special protocol for pilots on insulin pumps, which are not guaranteed to function if there is a sudden loss of cabin pressure.
Dr. Hine and her colleague David Russell-Jones, MD, who is the program’s medical director, presented 4 years’ worth of data on 16 of the 26 pilots who have participated in the program. All of these pilots are otherwise healthy men with well-controlled diabetes who were deemed at low risk for glycemic events. They are an average of 40 years old with an average disease duration of 8 years. Their average HbA1c was 53 mmol/l before licensure and 54.8 mmol/l afterwards. All of the pilots have normal renal function, no retinopathy, no changes in blood pressure, and good awareness of hypoglycemia.
Among them, they have accumulated 4,900 flight hours and 8,897 blood glucose readings. Most of the flights (88%) were medium- or short-haul flights of less than 6 hours.
Even though 96% of readings fell into the 5-20 mmol/l green range, the bulk of those readings were in the range of 5-9 mmol/l. There was very little hourly variation in blood glucose levels during flights up to 6 hours, showing that the protocol is effective at establishing stable glycemia.
Right now, the program is in place only for current pilots who have a new diagnosis of diabetes. But, said Dr. Russell-Jones, it may be expanded at some point to encompass people with diabetes who wish to train to become a commercial pilot.
Neither Dr. Hines nor Dr. Russell-Jones reported any financial conflicts.
On Twitter @Alz_Gal
AT EASD 2016
Key clinical point: A protocol of regular blood glucose monitoring during flight is keeping British commercial pilots in the air.
Major finding: Of 8,897 blood glucose readings, only 22 were in the dangerous “red” range that demands handing over control of the plane to the copilot.
Data source: The 16 pilots in the program have amassed 4,900 flight hours.
Disclosures: Neither Dr. Hine nor Dr. Russell-Jones had any financial disclosures.
