In high‑risk people with heart disease and extra weight but no diabetes, this “skinny jab” also clearly lowered heart attacks and strokes over several years.
Weekly semaglutide 2.4 mg cut major cardiovascular events by 20% in people with obesity, established CVD, and no diabetes. The SELECT trial was a multicentre, double‑blind RCT enrolling 17,604 adults ≥45 years with BMI ≥27 and established atherosclerotic CVD but no history of diabetes, randomised to once‑weekly semaglutide 2.4 mg or placebo plus standard care. Over a mean 39.8 months’ follow‑up, the primary composite (CV death, non‑fatal MI, non‑fatal stroke) occurred in 6.5% of the semaglutide group vs 8.0% of placebo (HR 0.80; 95% CI 0.72–0.90). Prespecified analyses show this benefit is consistent across baseline HbA1c categories (normoglycaemia vs pre‑diabetes) and across adiposity strata, suggesting mechanisms beyond glycaemic control alone. Semaglutide produced sustained ~10–11% mean weight loss at 4 years vs ~1–2% with placebo, but with higher discontinuation mainly due to GI side‑effects (discontinuation ~16–27% vs ~8–24%, depending on analysis).
Wilding JPH et al., “Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes,” New England Journal of Medicine, PMID: 37952131
Deanfield J et al., “Semaglutide and cardiovascular outcomes by baseline glycemia (SELECT analysis),” Diabetes Care 2024 (PMCID: PMC11282385).
My Take:
SELECT is a large, event‑driven RCT with hard outcomes and robust analyses, this is very high‑quality evidence. However, the enrolled population is specific: established CVD plus overweight/obesity; we do not have equivalent outcomes data for primary prevention in lower‑risk individuals or lean patients. Long‑term (>5–10 year) safety, cost‑effectiveness, and the impact of widespread use (including in lower‑risk groups) remain open questions.
For clinicians; continue to emphasise lifestyle foundations: diet quality, physical activity, sleep, BP and lipid control must remain first‑line; in SELECT, semaglutide was layered on top of standard care, not a substitute for it.
#Semaglutide #SELECTTrial #CardiovascularHealth #GLP1 #ObesityMedicine #Longevity #HeartHealth #EvidenceBasedMedicine #ClinicalTrials #Healthspan
