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. |
SELECT: Kidney Outcomes of Semaglutide
RCT · obesity + CVD, no diabetes · median 3.4 y
Semaglutide 2.4 mg lowered the composite kidney endpoint by 22% (HR 0.78) and slowed eGFR decline in adults with obesity and CVD without diabetes, with greater benefit when baseline eGFR was below 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