Semaglutide for reducing the risk of major adverse cardiovascular events in people with cardiovascular disease and overweight or obesity

There is evidence for the use of semaglutide 2.4mg per day reducing risk of cardiovascular events in patients with obesity without diabetes from the SELECT trial (1):

SELECT trial - semaglutide and cardiovascular outcomes in patients with obesity without diabetes

• multicentre, double-blind, randomized, placebo-controlled, event-driven superiority trial, we enrolled patients 45 years of age or older who had preexisting cardiovascular disease and a body-mass index of 27 or greater but no history of diabetes. Patients were randomly assigned in a 1:1 ratio to receive once-weekly subcutaneous semaglutide at a dose of 2.4 mg or placebo
  • primary cardiovascular end point was a composite of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke in a time-to-first-event analysis
• total of 17,604 patients were enrolled; 8803 were assigned to receive semaglutide and 8801 to receive placebo
• mean (+/-SD) duration of exposure to semaglutide or placebo was 34.2+/-13.7 months, and the mean duration of follow-up was 39.8+/-9.4 month
  • primary cardiovascular end-point event occurred in 569 of the 8803 patients (6.5%) in the semaglutide group and in 701 of the 8801 patients (8.0%) in the placebo group (hazard ratio, 0.80; 95% confidence interval, 0.72 to 0.90; P<0.001)
  • number needed to treat (NNT) for the primary endpoint (3-point MACE: cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) was approximately 67 over a mean follow-up of 39.8 months
    • this represents the number of patients with overweight or obesity and established CVD (without diabetes) who needed to be treated with semaglutide 2.4mg to prevent one MACE

NICE have stated that (2):

Semaglutide (up to a maintenance dose of 2.4 mg once weekly) can be used, within its marketing authorisation, alongside a reduced-calorie diet and increased physical activity, as an option for reducing the risk of a major adverse cardiovascular event (that is, cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in adults with both:

• established cardiovascular disease (CVD), defined as at least 1 of the following:
  • previous myocardial infarction
  • previous ischaemic or haemorrhagic stroke
  • symptomatic peripheral arterial disease (they have intermittent claudication with an ankle-brachial index of less than 0.85 at rest, or have had a peripheral arterial revascularisation procedure or an amputation because of atherosclerotic disease),
• and

• a body mass index (BMI) of at least 27 kg/m²

The NICE Committee note “…Standard care for established CVD in people with a BMI of at least 27 kg/m² includes lifestyle changes and medicines aimed at reducing the risk of a major adverse cardiovascular event.

Clinical trial evidence shows that semaglutide plus standard care reduces the risk of a major adverse cardiovascular event compared with placebo plus standard care in this population…”

Reference:

1. Lincoff AM et al; SELECT Trial Investigators. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023 Nov 11. doi: 10.1056/NEJMoa2307563. Epub ahead of print. PMID: 37952131
2. NICE (May 2026). Semaglutide for reducing the risk of major adverse cardiovascular events in people with cardiovascular disease and overweight or obesity.