Summary: In a pre-specified secondary kidney analysis of the SELECT trial (17,604 adults with overweight or obesity and established cardiovascular disease, without diabetes), once-weekly semaglutide 2.4 mg reduced a composite kidney endpoint versus placebo (1.8% vs 2.2%; HR 0.78, 95% CI 0.63 to 0.96; P = 0.02), with a small eGFR benefit at 104 weeks (0.75 ml/min/1.73 m2; P < 0.001) that was larger in those with baseline eGFR below 60.
PICO Summary
| Element | Detail |
|---|---|
| Population | 17,604 adults with overweight or obesity (BMI ≥27) and established cardiovascular disease, without diabetes; double-blind randomised controlled trial (SELECT), multinational (41 countries). |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg (n = 8,803). |
| Comparison | Matching placebo once weekly (n = 8,801). |
| Outcome | Pre-specified composite kidney endpoint (kidney death, chronic kidney replacement therapy, persistent eGFR <15, persistent ≥50% eGFR reduction, or persistent macroalbuminuria): 1.8% vs 2.2%; HR 0.78 (95% CI 0.63 to 0.96; P = 0.02); absolute risk reduction approximately 0.4%, NNT approximately 250 over the trial. eGFR treatment benefit at 104 weeks: 0.75 ml/min/1.73 m2 (95% CI 0.43 to 1.06; P < 0.001) overall, and 2.19 ml/min/1.73 m2 (95% CI 1.00 to 3.38; P < 0.001) in those with baseline eGFR <60. |
SELECT: kidney outcomes of semaglutide
RCT (secondary) · obesity + CVD, no diabetes · ~3.3 yr
Semaglutide 2.4 mg modestly cut a composite kidney endpoint (HR 0.78) versus placebo in overweight or obese adults with CVD but no diabetes. The benefit was small in absolute terms and driven largely by albuminuria, so it supports rather than establishes a kidney indication.
Expert Commentary
This pre-specified secondary analysis of a large, well-conducted randomised trial suggests a genuine but modest kidney signal for semaglutide 2.4 mg in people with overweight or obesity and cardiovascular disease who do not have diabetes. Because randomisation is preserved, the composite-endpoint difference can be read as causal within this trial, yet the verdict should stay measured. The relative reduction of 22% is driven by a small absolute gap (1.8% versus 2.2%), so roughly 250 patients would need treatment to prevent one composite kidney event over the study period, and the components were dominated by changes in albuminuria rather than hard outcomes such as kidney replacement therapy. The 104-week eGFR advantage was real but slight overall, becoming more meaningful only in the subgroup with reduced baseline function. The principal limitation is that kidney endpoints were secondary, the trial was not powered for them, and the population was selected for cardiovascular risk, which limits generalisability. The trial was funded by the manufacturer, Novo Nordisk, with several authors employed by the sponsor, so independent replication is desirable. Can I use this with my patients? Reasonably, for an overweight or obese adult with established cardiovascular disease and early kidney decline who already merits semaglutide for cardiometabolic reasons, this strengthens the rationale rather than creating a standalone kidney indication. Dedicated kidney-outcome trials in this non-diabetic population are needed before semaglutide is positioned as nephroprotective therapy.
References
Colhoun HM, Lingvay I, Brown PM, Deanfield J, Brown-Frandsen K, Kahn SE, et al. Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial. Nat Med. 2024;30(7):2058-2066. doi:10.1038/s41591-024-03015-5