Semaglutide and GLP-1 Cardiovascular Risk Reduction
Semaglutide is now the second GLP-1 analogue approved for reducing cardiovascular disease (CVD) events in patients with type 2 diabetes.
An injectable formulation of the glucagon-like peptide-1 (GLP-1) analogue semaglutide (Ozempic) is now approved by the U.S. Food and Drug Administration for reducing major adverse cardiovascular events in patients with type 2 diabetes. The manufacturer announced this regulatory decision recently.
Specifically, semaglutide is indicated to reduce the risk of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in adults with type 2 diabetes and established cardiovascular disease. This indication is based on results from the SUSTAIN-6 randomized clinical trial.
Clinical Evidence From the SUSTAIN-6 Trial
The SUSTAIN-6 trial enrolled 3,297 subjects. Most participants had cardiovascular disease, chronic kidney disease, or both.
In this study, semaglutide treatment on top of usual care reduced the risk of major adverse cardiovascular events by 26% compared with usual care plus placebo. The median follow-up period was 2.1 years.
Overall, the primary outcome occurred in 8.9% of patients receiving placebo and 6.6% of patients receiving semaglutide. Statistical analysis confirmed noninferiority (P < 0.001) and superiority (P = 0.02).
Regulatory Background and Related GLP-1 Therapies
The subcutaneous injection of semaglutide received approval for glycemic control in patients with type 2 diabetes in 2017. It has now become the second GLP-1 agonist approved for reducing clinical cardiovascular events.
In the same year, regulators expanded the indication for liraglutide (Victoza) to include reduction of cardiovascular death, myocardial infarction, or stroke. In addition, several sodium-glucose co-transporter 2 (SGLT2) inhibitors have gained approval for reducing cardiovascular events.
Oral Semaglutide and Cardiovascular Safety Data
Regulators also updated the label for the oral formulation of semaglutide (Rybelsus). The update indicates that available data support its cardiovascular safety profile.
This labeling change does not represent an expanded claim for cardiovascular benefit. In the PIONEER 6 cardiovascular outcomes study, oral semaglutide demonstrated noninferiority to placebo for the primary endpoint of cardiovascular death, myocardial infarction, or stroke when added to usual care.