Summary: In a pre-specified analysis of the SELECT trial (17,604 adults with overweight or obesity and established cardiovascular disease, without diabetes), once-weekly semaglutide 2.4 mg lowered the composite kidney endpoint to 1.8% versus 2.2% with placebo (HR 0.78; 95% CI 0.63 to 0.96; P = 0.02). The 104-week treatment benefit on eGFR was modest overall (0.75 mL/min/1.73 m2) and larger in those with baseline eGFR below 60 mL/min/1.73 m2 (2.19 mL/min/1.73 m2).
PICO Summary
| Element | Detail |
|---|---|
| Population | 17,604 adults with overweight or obesity (BMI 27 or higher) and established cardiovascular disease, without diabetes. Multinational, double-blind RCT (SELECT; NCT03574597); pre-specified kidney analysis. |
| Intervention | Once-weekly subcutaneous semaglutide 2.4 mg (n = 8,803). |
| Comparison | Matching placebo injection (n = 8,801). |
| Outcome | Main composite kidney endpoint (kidney death, chronic kidney replacement therapy, persistent eGFR below 15, persistent eGFR reduction of 50% or more, or persistent macroalbuminuria): 1.8% with semaglutide versus 2.2% with placebo; HR 0.78 (95% CI 0.63 to 0.96; P = 0.02), an absolute reduction of about 0.4 percentage points. eGFR 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
Landmark RCT · obesity + CVD, no diabetes · 104 weeks
Semaglutide 2.4 mg cut the composite kidney endpoint by 22% (HR 0.78) in non-diabetic obesity with CVD, but the low event rate and ~0.4-point absolute reduction make this a supportive signal rather than confirmed renal protection.
Expert Commentary
This pre-specified analysis suggests that semaglutide 2.4 mg confers a kidney signal in adults with obesity and cardiovascular disease but without diabetes, a group for whom renal protection has historically been demonstrated mainly in diabetic cohorts. The verdict is one of cautious encouragement rather than established benefit. The composite endpoint was reduced, yet the result was driven substantially by albuminuria, the event rate was low, and the absolute risk reduction was modest at roughly 0.4 percentage points, which tempers enthusiasm and would require a large number needed to treat over several years. The chief limitation is that SELECT was powered for cardiovascular events, not kidney outcomes, so these findings should be read as hypothesis-supporting and associational with respect to hard renal endpoints rather than confirmatory. It must also be noted that the trial was sponsored by the manufacturer and several authors were employed by it, which warrants the usual interpretive caution. Can I use this with my patients? It can reasonably inform shared decision-making for a patient with obesity and cardiovascular disease who is already a candidate for semaglutide on cardiometabolic grounds, but it should not yet be prescribed primarily for renal protection in this non-diabetic population. A dedicated kidney-outcome trial in this group would be welcome to confirm whether the signal translates into durable clinical benefit.
References
Colhoun HM, Lingvay I, Brown PM, 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