FDA approves including CV safety data in insulin degludec label

The FDA approved updates to the prescribing information for insulin degludec to include data from the DEVOTE safety outcomes trial, Novo Nordisk announced in a press release.

In the DEVOTE cardiovascular outcomes trial, insulin degludec (Tresiba), a new-generation, ultra-long-acting basal insulin, was noninferior to insulin glargine (Lantus, Sanofi), a first-generation insulin, for the primary endpoint of major adverse cardiovascular events in patients with type 2 diabetes and atherosclerotic CVD and was associated with a 40% reduction in severe hypoglycemia. The findings were presented at the American Diabetes Association annual meeting last year.

“Tresiba is clinically proven to lower patients’ HbA1c levels, and now the updated label provides physicians with additional evidence to help guide treatment decisions,” Todd Hobbs, vice president and U.S. chief medical officer, Novo Nordisk, said in a statement. “Cardiovascular disease and severe hypoglycemia are two of the most profound concerns for people living with diabetes. Novo Nordisk is dedicated to research in these areas and believes in their importance to overall diabetes care.”

In the DEVOTE trial, a randomized, double-blind, treat-to-target, event-driven study, 7,637 patients with type 2 diabetes were enrolled at 436 sites in 20 countries between October 2013 and November 2014. Researchers randomly assigned 3,818 patients to receive insulin degludec 100 U/mL and 3,819 to receive insulin glargine U100 once per day between dinner and bedtime. At the beginning of the study, 85% had established CVD, chronic kidney disease or both. The mean age at baseline was 65 years, mean diabetes duration was 16 years, and mean HbA1c was 8.4%.

The primary composite outcome was first occurrence of a major CV event, including death from CV causes, nonfatal myocardial infarction or nonfatal stroke. The secondary outcome was severe hypoglycemia. Patients were followed for approximately 2 years.

At 2 years, major CV events occurred in 8.5% of the degludec group vs. 9.3% of the glargine group (HR = 0.91; 95% CI, 0.78-1.06; P < .001 for noninferiority). Further, results for each individual component of the primary composite endpoint were consistent: first occurrence of CV death (HR = 0.96; 95% CI, 0.76-1.21), nonfatal MI (HR = 0.85; 95% CI, 0.68-1.06) and nonfatal stroke (HR = 0.9; 95% CI, 0.65-1.23).

The degludec group had a significant reduction in the rate of severe hypoglycemia vs. the glargine group. The rate of prespecified adjudicated severe hypoglycemia was 6.6% in the glargine group vs. 4.9% in the degludec group (absolute difference, 1.7 percentage points; RR = 0.6; P < .001 for superiority; OR = 0.73; P < .001 for superiority). In addition, the rate of nocturnal severe hypoglycemia was significantly lower in the degludec group (RR = 0.47; 95% CI, 0.31-0.73). – by Regina Schaffer