Weekly GLP-1 analogue associated with reduced MI, stroke risk, industry study finds
The trial of semaglutide included 3,297 patients with type 2 diabetes, 83% of whom had established cardiovascular disease, chronic kidney disease, or both.
Semaglutide, a once-weekly glucagon-like peptide-1 analogue, reduced cardiovascular events compared to placebo, according to a manufacturer-sponsored trial.
The trial included 3,297 patients with type 2 diabetes, 83% of whom had established cardiovascular disease, chronic kidney disease, or both. They were randomized to once-weekly semaglutide at a dose of 0.5 mg or 1.0 mg or placebo for 2 years. The primary composite outcome was the first occurrence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke. Results were published by the New England Journal of Medicine on Sept. 16.
The primary outcome occurred in 6.6% of the semaglutide group and 8.9% of the placebo group (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95; P<0.001 for noninferiority). The difference between groups was driven by a significant reduction in nonfatal stroke (1.6% vs. 2.7%; HR, 0.61; 95% CI, 0.38 to 0.99) and an insignificant reduction in nonfatal myocardial infarction (2.9% vs. 3.9%; HR, 0.74; 95% CI, 0.51 to 1.08). Cardiovascular deaths were similar between groups. New or worsening nephropathy was less common in the semaglutide group, but rates of retinopathy complications were significantly worse.
The study was designed to meet regulatory requirements regarding cardiovascular safety of new diabetes medications, and it proved the noninferiority of semaglutide on these outcomes, the study authors concluded. The number needed to treat with the drug to prevent 1 event in the primary outcome over 2 years would be 45 patients, they calculated. The authors noted that patients taking the drug had reductions in HbA1c, body weight, and systolic blood pressure compared to controls and that the observed retinopathy complications could be an effect of rapid glucose reductions, although they could also be a direct effect of the drug.
Limitations include that superiority of the drug was not a prespecified outcome in the study and that patients were followed for only slightly more than 2 years and were at high cardiovascular risk. “The generalizability of these findings to other populations and a longer duration of treatment is unknown. It is also unknown to what extent the greater glycated hemoglobin reductions in the semaglutide group contributed to the results,” the study authors wrote.