Semaglutide, a glucagon-like peptide-1 receptor agonist monotherapy available in both subcutaneous as well as oral forms, is an approved second-line treatment option for glycemic control in type 2 diabetes. A recent study published in The New England Journal of Medicine has concluded that a 2.4 mg weekly dose of subcutaneous semaglutide is more effective than placebo in reducing mortality due to cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in overweight or obesity patients with preexisting cardiovascular disease but without diabetes.
Lincoff and colleagues determined the effectiveness of semaglutide in reducing the risk of cardiovascular events in patients who are overweight or obese and have a history of cardiovascular disease. The multicenter, double-blind, randomized, and placebo-controlled trial enrolled 17,604 patients aged ≥45 years with preexisting cardiovascular disease and a body mass index of 27 or higher, but no history of diabetes. The patients were randomly assigned in a 1:1 ratio to receive either a once-weekly subcutaneous dose of 2.4 mg of semaglutide or a placebo. The primary cardiovascular endpoint was a combination of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis, and safety was also assessed.
Among the enrolled subjects, 8,803 were prescribed semaglutide, while 8,801 received a placebo. The average duration of treatment with semaglutide or placebo was 34.2±13.7 months, and the average follow-up period was 39.8±9.4 months. During the trial, 6.5% of patients in the semaglutide group experienced a primary cardiovascular event, compared to 8.0% in the placebo group. This indicates a significant difference, with a hazard ratio of 0.80 and a 95% confidence interval of 0.72 to 0.90 (P<0.001).
Similarly, Nauck and Quast investigated the safety of semaglutide compared to a placebo in patients with cardiovascular conditions as an addition to standard care. This examination was conducted through two trials: the Semaglutide Unabated Sustainability in the Treatment of Type 2 Diabetes (SUSTAIN) 6 trial, which involved the once-weekly subcutaneous formulation, and the Peptide Innovation for Early Diabetes Treatment (PIONEER) 6 trial, focusing on the newly developed once-daily oral formulation. The study found that in patients with preexisting cardiovascular disease who were overweight or obese but did not have diabetes, a weekly dose of 2.4mg of subcutaneous semaglutide was more effective than a placebo in reducing the risk of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke over a mean follow-up period of 39.8 months.
The study findings add to the growing body of evidence supporting the multifaceted benefits of semaglutide. These findings not only reinforce the drug’s therapeutic potential but also highlight its relevance in enhancing cardiovascular outcomes within a high-risk demographic population.
References
- Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Nov 11.
- Nauck MA, Quast DR. Cardiovascular Safety and Benefits of Semaglutide in Patients with Type 2 Diabetes: Findings from SUSTAIN 6 and PIONEER 6. Frontiers in Endocrinology [Internet]. 2021 [cited 2023 Nov 14];12.