Prevention & lipidsSecondary analysis
Efficacy and Safety of Semaglutide According to Frailty Status
- Secondary analysis of the SELECT randomised trial
Authors' conclusion
This study found that semaglutide demonstrated beneficial effects on a broad range of clinical outcomes in SELECT, without detectable heterogeneity by baseline FI. Benefits of semaglutide on health-related quality of life appeared greater with higher FI.
Study context
- Population
- Adults with BMI ≥27 and established CVD without diabetes, categorised by 31-item frailty index (FI): not frail (FI ≤0.210), more frail (FI 0.211–0.310), most frail (FI ≥0.311)
- Participants
- 17,604 adults
- Comparison
- Semaglutide vs placebo, by frailty index category
- Primary endpoint
- CV death, nonfatal MI and nonfatal stroke
Primary result
As reported in the abstract
CV death, nonfatal MI or nonfatal stroke, by FI category
Semaglutide vs PlaceboHazard ratio (95% CI)
FI ≤0.210 (not frail)
0.84(0.65–1.07)
FI 0.211-0.310 (more frail)
0.70(0.59–0.82)
FI ≥0.311 (most frail)
0.92(0.76–1.10)
- Similar findings with FI examined continuously
- P = 0.30 for interaction
Further findings
| Outcome | OR (95% CI) | |
|---|---|---|
| Change in FI category · baseline to week 104 — Semaglutide vs Placebo · improvement | 2.46 (1.80–3.37) | |
| Change in FI category · baseline to week 104 — Semaglutide vs Placebo · worsening | 0.47 (0.34–0.65) | |
| 0.20.5125Odds ratio (log scale) |
Composite HF outcome, all-cause hospitalisation, all-cause mortality
- Semaglutide reduced composite HF outcome regardless of FI category
- P = 0.82 for interaction
- Semaglutide reduced all-cause hospitalization regardless of FI category
- P = 0.71 for interaction
- Semaglutide reduced all-cause mortality regardless of FI category
- P = 0.28 for interaction
EQ-5D-5L score
- Benefits of semaglutide appeared larger with higher FI
- P = 0.02 for interaction
Safety
AEs leading to permanent discontinuation
- HRs for semaglutide vs placebo appeared lower with higher baseline FI
- P < 0.001 for interaction
Original publication
Efficacy and Safety of Semaglutide According to Frailty Status. JAMA Cardiol. Published 16 September 2026. doi:10.1001/jamacardio.2026.3566
Summarised from the published abstract; every number is checked against it