Patients with type 2 diabetes who were at high cardiovascular risk and received semaglutide had a significant 26 percent lower risk of the composite endpoint of cardiovascular death, nonfatal MI or nonfatal stroke compared with a placebo group, according to a randomized trial.
The semaglutide group had a 39 percent decrease in the rate of nonfatal stroke and a 26 percent decrease in the rate of nonfatal MI. The rates of cardiovascular death were similar between the groups.
Lead researcher Steven P. Marso, MD, of the Research Medical Center in Kansas City, Missouri, and colleagues published their results online Sept. 16 in the New England Journal of Medicine.
The findings were also presented at the European Association for the Study of Diabetes annual meeting in Munich, Germany.
Semaglutide, a once-weekly glucagon-like peptide 1 analogue from Novo Nordisk, is not FDA-approved. Novo Nordisk designed and funded this study, which was known as SUSTAIN-6. The company launched the SUSTAIN clinical program to evaluate semaglutide in six global clinical trials involving more than 7,000 adults with type 2 diabetes and two Japanese trials involving approximately 2,000 adults with type 2 diabetes.
In the SUSTAIN-6 study, the researchers randomly assigned 3,297 patients with type 2 diabetes from February 2003 to December 2003 to receive 0.5 mg or 1.0 mg of semaglutide once weekly or placebo for 104 weeks. The patients were required to be at least 50 years old with established cardiovascular disease, chronic heart failure or chronic kidney disease or at least 60 years old with at least one cardiovascular risk factor.
The mean duration of type 2 diabetes was 13.9 years and the mean glycated hemoglobin level was 8.7 percent. Of the patients, 83 percent had established cardiovascular disease, 58.8 percent had established cardiovascular disease without chronic kidney disease, 10.7 percent had chronic kidney disease only and 13.4 percent had cardiovascular disease and kidney disease.
After a median observation time of 2.1 years, the primary composite outcome of the first occurrence of cardiovascular death, nonfatal MI or nonfatal stroke occurred in 6.6 percent of the semaglutide group and 8.9 percent of the placebo group. The difference was statistically significant.
The researchers said that 45 patients would need to be treated to prevent one event of the primary outcome during a 24-month period. They added that patients in the semaglutide group had a lower risk of new or worsening nephropathy and had larger reductions in glycated hemoglobin levels. However, they had a higher risk of diabetic retinopathy complications such as vitreous hemorrhage, blindness or the need for treatment with an intravitreal agent or photocoagulation.
The researchers mentioned that this was a noniferiority study and was not powered to show the superiority of semaglutide. They also mentioned that the generalizability of the findings to other populations and a longer treatment duration was unknown.