At the American Heart Association's (AHA) Scientific Sessions 2023, the Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) trial¹ was presented demonstrating that 2.4mg once weekly subcutaneous semaglutide in adults with atherosclerotic cardiovascular disease (ASCVD) and body mass index ≥27 kg/m² but no diabetes mellitus (DM) resulted in 20% reduction in death from cardiovascular (CV) causes, nonfatal myocardial infarction, or nonfatal stroke over a mean follow up of 39.8 months as compared to placebo.

The substantial improvement in the primary composite CV endpoint achieved in this well-orchestrated multicenter, double-blind, randomized, placebo-controlled, event-driven superiority trial conducted at 804 clinical sites in 41 countries is practice changing. Semaglutide recently received a Food and Drug Administration indication for secondary CV disease prevention in obese patients without DM. This is an add on to baseline therapy for established ASCVD which would be at a minimum high intensity statin therapy and single antiplatelet therapy with some patients on multiple lipid-lowering agents, dual anti-platelet therapy, beta-blockers, angiotensin-converting-enzyme inhibitors/angiotensin-receptor blocker/angiotensin receptor neprilysin inhibitor and/or low dose colchicine. Thus, the challenge for clinicians will be to effectively and safely fold this into the care plan of their individual patients, and to establish its priority compared to the other options.

Adding to this challenge is the inflated cost of the drug and the need for weekly injections. Another clinical consideration is the side effects that occur with semaglutide. In the SELECT trial, the most common adverse event in the semaglutide group was gastrointestinal complaints and these led to higher rates of permanent discontinuation of the drug than the placebo group (880 patients [10.0%] and 172 patients [2.0%] respectively [p<0.001]).

Semaglutide is already widely used in Type 2 DM. Future studies to assess real world implementation of semaglutide therapy for its weight loss and CV indication are needed, and strategies to overcome cost and accessibility barriers will be required. At this time, there is evidence and promise that the use of the weight loss dose of semaglutide may help to mitigate CV disease risk in overweight or obese patients without DM.

References

1. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al., on behalf of the SELECT Trial Investigators. Semaglutide and cardiovascular outcomes in obesity without diabetes. N Engl J Med 2023;389:2221-32.