The glucagon-like peptide-1 receptor agonist semaglutide significantly lowers the risk for cardiovascular death, nonfatal myocardial infarction or nonfatal stroke in adults with type 2 diabetes at high cardiovascular risk, according to findings presented at the 52nd European Association for the Study of Diabetes Annual Meeting and published in The New England Journal of Medicine.
Researchers evaluated data from the SUSTAIN 6 trial on 3,297 adults (mean age, 64.6 years) with type 2 diabetes (mean HbA1c, 8.7%) on a standard care regimen randomly assigned once-weekly semaglutide (Novo Nordisk) 0.5 mg or 1 mg or placebo for 104 weeks.
“SUSTAIN 6 is a CV safety study performed under the FDA mandate for a phase 3 trial, and because it was a phase 3 trial, safety data were also carefully collected,” Lawrence A. Leiter, MD, director of the Lipid Clinic, associate director of the Clinical Nutrition and Risk Factor Modification Centre and associate scientist at Li Ka Shing Knowledge Institute at St. Michael’s Hospital in Toronto, said during a presentation.
First occurrences of CV death, nonfatal MI or nonfatal stroke were the primary outcomes.
“Participants had to be 50 years or older with clinical evidence of CVD or 60 years or older with subclinical evidence of CVD,” Leiter said. “Previous treatment could include zero to two oral agents with or without the addition of basal insulin. Baseline HbA1c had to be 7% or higher with no upper limit.”
Eighty-three percent of participants had established CVD (including chronic kidney disease stage 3 or higher), 58.8% had established CVD without CKD, 10.7% had CKD only, and 13.4% had both CVD and CKD.
The primary outcome of first occurrence to CV death, nonfatal MI or nonfatal stroke occurred in 6.6% of the semaglutide group (108 events) and 8.9% of the placebo group (146 events; HR = 0.74; 95% CI, 0.58-0.95). Both groups experienced similar rates of CV death (semaglutide, 44 events; placebo, 46 events). Compared with placebo, the semaglutide group experienced less nonfatal MI (HR = 0.74; 95% CI, 0.51-1.08) and nonfatal stroke (HR = 0.61; 95% CI, 0.38-0.99).
When an expanded composite CV outcome, including first occurrence of CV death, nonfatal MI, nonfatal stroke, revascularization and unstable angina requiring hospitalization or hospitalization for heart failure was evaluated, the semaglutide group experienced fewer events (12.1%) compared with placebo (16%; HR = 0.74; 95% CI, 0.62-0.89).
HbA1c decreased more in the semaglutide groups (0.5 mg, 1.1%; 1 mg, 1.4%) compared with the placebo group (0.4%; P < .0001). Similarly, participants in the semaglutide groups were more likely to reach HbA1c targets of less than 7% or 6.5% or less compared with the placebo groups (P < .0001 for all).
The semaglutide group experienced significantly higher rates of retinopathy complications compared with the placebo group (HR = 1.76; 95% CI, 1.11-2.78). Sixty-six participants had retinopathy complications at baseline (84% in the semaglutide group, 82.8% of the placebo group). New or worsening nephropathy was less common in the semaglutide group (3.8%) compared with the placebo group (6.1%; HR = 0.64; 95% CI, 0.46-0.88).
All participants experienced similar numbers and occurrence rates of severe hypoglycemic episodes or hypoglycemia.
“Among patients with type 2 diabetes at high [CV] risk, the rate of first occurrence of death from [CV] causes, nonfatal [MI] or nonfatal stroke was significantly lower in those receiving semaglutide than in those receiving placebo, which confirmed noninferiority,” the researchers wrote. – by Amber Cox
Leiter, et al. SUSTAIN 6. Presented at: 52nd EASD Annual Meeting; Sept. 12-16, 2016; Munich.
Marso SP, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1607141.
Disclosure: The trial was funded by Novo Nordisk. Leiter reports various financial ties with Aegerion, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novo Nordisk, Pfizer, Sanofi and Servier and The Medicines Company. Please see the full study for a list of all other authors’ relevant financial disclosures.