Summary: In a pre-specified secondary analysis of the SELECT trial (n=17,604 adults with overweight or obesity and established cardiovascular disease, without diabetes), once-weekly semaglutide 2.4 mg lowered a composite kidney endpoint versus placebo (1.8% vs 2.2%; HR 0.78, 95% CI 0.63 to 0.96; P=0.02) and produced a small eGFR benefit at 104 weeks (0.75 ml/min/1.73 m2 overall; 2.19 ml/min/1.73 m2 in those with baseline eGFR below 60).
PICO Summary
| Element | Detail |
|---|---|
| Population | 17,604 adults with overweight or obesity (BMI at least 27) and established cardiovascular disease, without diabetes; pre-specified secondary kidney analysis of the multinational, double-blind SELECT randomised controlled trial (NCT03574597). |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg (n=8,803), added to standard care. |
| Comparison | Once-weekly matching placebo (n=8,801), added to standard care. |
| Outcome | Main composite kidney endpoint (kidney death, chronic kidney replacement therapy, persistent eGFR below 15 ml/min/1.73 m2, persistent 50% or greater 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 percentage points. eGFR treatment benefit at 104 weeks: 0.75 ml/min/1.73 m2 overall (95% CI 0.43 to 1.06; P<0.001) and 2.19 ml/min/1.73 m2 in those with baseline eGFR below 60 ml/min/1.73 m2 (95% CI 1.00 to 3.38; P<0.001). |
SELECT: Kidney Outcomes of Semaglutide
RCT secondary analysis · obesity + CVD, no diabetes · ~3 yr
Once-weekly semaglutide 2.4 mg modestly cut a composite kidney endpoint (HR 0.78) and slowed eGFR decline in adults with obesity and cardiovascular disease but no diabetes. The benefit is real but small and driven by softer components, so it is supportive rather than a standalone reason to start treatment.
Expert Commentary
This pre-specified secondary analysis of the SELECT trial supports a modest renoprotective signal for semaglutide 2.4 mg in adults who have overweight or obesity and cardiovascular disease but not diabetes, a population in which kidney effects had not previously been well characterised. The composite endpoint was met with a relative risk reduction of about 22 percent, although the absolute difference was small (1.8 percent versus 2.2 percent over a median of roughly three years), so the number needed to treat is large and the result is driven mainly by softer components such as macroalbuminuria rather than by hard endpoints like kidney replacement therapy. The eGFR slope benefit was statistically robust and most pronounced in those with baseline eGFR below 60, which is biologically reasonable. The principal limitation is that kidney outcomes were a secondary analysis of a trial powered for cardiovascular events, so this is hypothesis-strengthening rather than definitive, and event numbers were low. The trial was sponsored by the manufacturer (Novo Nordisk) with several authors as employees, which warrants the usual caution despite the double-blind design. Can I use this with my patients? Reasonably yes, as supportive context when counselling a patient with obesity and cardiovascular disease about the broader benefits of semaglutide, but not as a standalone reason to start it for kidney protection. Dedicated kidney-outcome trials in this non-diabetic group are needed to confirm the effect.
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