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DEVOTE: Insulin degludec demonstrates CV safety, reduced risk for severe hypoglycemia
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SAN DIEGO — In the DEVOTE cardiovascular outcomes trial, insulin degludec was noninferior to insulin glargine for the primary endpoint of major adverse cardiovascular events and was associated with significant reductions in severe hypoglycemia among high-risk patients with type 2 diabetes.
The randomized, double blind, treat-to-target, event-driven, CV outcomes trial included 7,637 patients with type 2 diabetes 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 (Tresiba, Novo Nordisk), a new-generation, ultra-long-acting basal insulin, and 3,819 to receive insulin glargine U100 (Lantus, Sanofi), a first-generation insulin, once per day between dinner and bedtime.
“Complications from cardiovascular disease really remain an unmet challenge and unmet clinical need for patients with type 2 diabetes,” Steven P. Marso, MD, chief medical officer for HCA Midwest Health cardiovascular services, said during a press conference at the American Diabetes Association Scientific Sessions.
In prior open-label studies, insulin degludec has been linked with lower rates of hypoglycemia and lower day-to-day glucose variability compared with older insulins; however, there is a need for more data on the CV safety of insulin degludec, according to Marso and colleagues.
Patients enrolled were at high risk for CV events. 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), according to findings presented here and simultaneously published in The New England Journal of Medicine.
“Insulin degludec was as safe as insulin glargine with respect to CV outcomes,” Marso said.
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).
In other results, mean HbA1c was 7.5% in both groups at 2 years. Mean fasting plasma glucose was significantly lower at follow-up in the degludec group vs. the glargine group (128 mg/dL vs. 126 mg/dL; P < .001).
Rates of adverse events were similar between the two treatment groups.
“These results will provide reassurance for both people with type 2 diabetes and their health care providers that this new insulin product has comparable cardiovascular safety to insulin glargine,” John B. Buse, MD, PhD, director of the Diabetes Center, director of the NC Translational and Clinical Sciences Institute and executive associate dean for clinical research at the University of North Carolina School of Medicine in Chapel Hill, said in a press release. “It is exciting that with insulin degludec, patients can achieve positive glycemic control along with a major reduction in the risk of severe hypoglycemia, particularly nocturnal severe hypoglycemia.” – by Katie Kalvaitis
References:
Marso SP. Symposium 3-CT-SY22. Presented at: American Diabetes Association 77th Scientific Sessions; June 9-13, 2017; San Diego.
Marso SP, et al. N Engl J Med. 2017;doi:10.1056/NEJMoa1615692.
Disclosures: Buse reports financial ties with various device and pharmaceutical companies. Marso reports financial ties with Abbott Vascular, AstraZeneca, Boston Scientific, Bristol-Myers Squibb and Novo Nordisk.