Diabetes: DEVOTE study shows cardiovascular safety of insulin degludec

The data, presented at the 77th ADA congress in San Diego and published in the New England Journal of Medicine, demonstrate a non-increased risk of major cardiovascular complications as well as a significant reduction in severe hypoglycemia compared to insulin glargine 100 U

Presented today at the 77th ADA (American Diabetes Association) conference in San Diego, and published simultaneously in the New England Journal of Medicine 1 , were the results of the DEVOTE study. First cardiovascular, randomized, treat-to-target, double-blind, event-driven outcome study involving 7.637 adults with type 2 diabetes at high cardiovascular risk, followed for about two years, whose objective was to confirm the cardiovascular safety of insulin degludec (Tresiba ® , Novo Nordisk) compared with insulin glargine 100 U.

The DEVOTE study showed that insulin degludec does not increase the risk of major cardiovascular complications: the primary endpoint of non-inferiority to insulin glargine 100 U is, in fact, achieved, with a hazard ratio (HR) of major cardiovascular complications (in terms of the composite endpoint, MACE) of 0.91 percent (95 percent confidence interval [CI]: 0.78; 1.06, p=0.209). The same is shown for the individual items comprising the cardiovascular composite endpoint, namely: death from cardiovascular causes (HR=0.96, 95 percent CI: 0.76; 1.21, p=0.714), nonfatal myocardial infarction (HR=0.85, 95 percent; CI: 0.68; 1.06, p=0.150), nonfatal stroke (HR=0.90, 95 percent CI: 0.65; 1.23, p=0.502). 1

The results of the study’s secondary endpoints also show that insulin degludec significantly reduced episodes of severe hypoglycemia (-40 percent; p>0.001), particularly those with nocturnal diabetes (-53 percent; p>0,001).*

Finally, post-hoc analysis demonstrates significantly lower fasting blood glucose values after two years in patients treated with insulin degludec, compared with insulin glargine 100 U (estimated treatment difference -7.2 mg/dL, p<0.001), while the level of glycemic control between patients treated with the two basal insulins was similar, with a difference in glycated hemoglobin (HbA_1c) at the end of treatment estimated to be around 0.01 percent (p=0.779). 1

“The risk of having cardiovascular complications and episodes of hypoglycemia are the main concerns for a person with type 2 diabetes. The results of the DEVOTE study therefore provide information that is destined to play a key role when choosing how to set therapy, precisely because they highlight the non-increased risk of major cardiovascular complications and the significant reduction in the rates of nocturnal severe and severe hypoglycemia compared with insulin glargine 100 U,” says Bernard Zinman of the Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Canada, a member of the DEVOTE Steering Committee.”.

The safety profile of insulin degludec found in the DEVOTE study is in line with previous studies. 1 In the DEVOTE study, the systematic collection of adverse events was limited to serious adverse events, i.e., those events leading to discontinuation of treatment with the assigned basal insulin type (5.2 percent of patients in the case of insulin degludec and 5.8 percent for insulin glargine 100 U), medical errors causing serious side effects, and side effects caused by technical problems.

*An episode of hypoglycemia is defined as severe when it requires assistance from another person and severe overnight if it takes place between the hours of 00:01 and 5:59 inclusive. 1

The DEVOTE Study

The DEVOTE study is a long-term, multinational, randomized, double-blind, event-driven study conducted to confirm the cardiovascular safety of insulin degludec compared with insulin glargine 100 U. In the study, 7.637 people with type 2 diabetes (3.818 on insulin degludec therapy, 3.819 with insulin glargine 100 U) at high cardiovascular risk were randomized to treatment with insulin degludec or insulin glargine 100 U in addition to standard therapy. 1

The primary endpoint of the DEVOTE study was the time from randomization to the occurrence of a cardiovascular event, falling among the following: death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke. Secondary endpoints referred to episodes of severe hypoglycemia, severe nocturnal hypoglycemia, glycated hemoglobin, and fasting blood glucose. 1

Insulin degludec

Insulin degludec (Tresiba ® ) is a daily single-dose basal insulin that provides a duration of action of more than 42 hours, with a stable blood glucose-lowering effect. 2,3 Insulin degludec appears to have low daily variability and a reduced risk of total, nocturnal, and severe hypoglycemia compared with insulin glargine 100 U. 1,2 When administration at the same time of day is not possible, insulin degludec allows more flexible dosing, with a minimum of eight hours and a maximum of forty between two consecutive administrations, while maintaining the same efficacy and safety profile. 2

Insulin degludec received its first regulatory approval in September 2012 and has since been approved in more than 80 countries worldwide. It is currently commercially available in more than 50 countries.

Novo Nordisk

Novo Nordisk is a multinational pharmaceutical company that has been a leader in the treatment of diabetes for more than ninety’years. This heritage has provided her with the skills and expertise to help people defeat additional chronic diseases: hemophilia, growth disorders and obesity’obesity. Novo Nordisk is based in Denmark and has about 42.000 employees in 77 countries and markets its products in more than 165 countries.