Summary:
In adults with overweight/obesity (BMI ≥27) and established atherosclerotic CVD, without diabetes, semaglutide 2.4 mg once weekly for median 3.4 years significantly reduced composite kidney endpoint (kidney failure, ≥50% eGFR decline, kidney death), slowed annual eGFR decline by 1.16 mL/min/1.73m², and reduced all-cause mortality by 20% compared to matching placebo, with fewer serious adverse events (49.6% vs 53.8%) and greater benefit in patients with baseline eGFR <60.
| PICO | Description |
|---|---|
| Population | Adults with overweight/obesity (BMI ≥27) and established CVD, without diabetes, from SELECT trial. |
| Intervention | Semaglutide 2.4 mg subcutaneously once weekly for median 3.4 years. |
| Comparison | Matching placebo weekly for same duration. |
| Outcome | Reduced kidney composite. eGFR decline slowed 1.16/yr. Mortality -20%. Greater benefit if eGFR <60. |
Clinical Context
SELECT established semaglutide as first obesity medication to reduce MACE. Obesity contributes to CKD through hemodynamic, metabolic, and inflammatory mechanisms.
Clinical Pearls
1. Kidney Protection Without Diabetes: Expands understanding beyond diabetes-focused trials.
2. Greater Benefit in Reduced eGFR Subgroup: Patients with eGFR <60 experienced more pronounced protection.
3. eGFR Preservation Quantified: 1.16 mL/min/1.73m²/year preservation compounds meaningfully over time.
4. Multi-Organ Protection Pattern: CV, kidney, and mortality benefits from single intervention.
Practical Application
Consider semaglutide 2.4 mg for comprehensive cardiorenal protection in obesity with CVD. Prioritize patients with concomitant CKD (eGFR <60).
Study Limitations
Kidney outcomes were secondary endpoints. Excluded diabetes. Longer follow-up needed for hard kidney outcomes.
Bottom Line
Semaglutide provides kidney protection alongside CV and mortality benefits in obesity with CVD, especially in those with eGFR <60.
Source: Colhoun HM, et al. “Long-term Kidney Outcomes of Semaglutide in Obesity and Cardiovascular Disease in the SELECT Trial.” Nature Medicine, 2024. Read article
