Summary: In adults with chronic kidney disease and overweight or obesity but without diabetes, semaglutide 2.4 mg once weekly for 24 weeks reduced urine albumin-to-creatinine ratio by 52% compared with placebo, with more frequent but expected gastrointestinal side effects.
PICO Summary
| Element | Detail |
|---|---|
| Population | Adults with CKD (eGFR ≥25 ml/min/1.73 m², UACR 30–3,500 mg/g) and BMI ≥27 without diabetes (n=101). |
| Intervention | Semaglutide 2.4 mg subcutaneous weekly for 24 weeks, titrated per protocol. |
| Comparison | Matching placebo injection weekly for 24 weeks. |
| Outcome | UACR reduced by 52.1% versus placebo (95% CI -65.5 to -33.4; P<0.0001). Gastrointestinal adverse events more frequent with semaglutide (30 vs 15 participants). |
Semaglutide in non-diabetic CKD with obesity
RCT · CKD + obesity, no diabetes · 24 weeks
Semaglutide 2.4 mg weekly cut albuminuria by 52% over 24 weeks in non-diabetic CKD with obesity. A surrogate endpoint in a small trial; hard kidney outcomes remain to be shown.
Expert Commentary
For the obese patient with proteinuric kidney disease but no diabetes, my toolkit has until now been an ACE inhibitor or ARB and, increasingly, an SGLT2 inhibitor, and I have been reaching the edge of what the evidence formally supports. This small trial interests me more than its size suggests, because it is the first randomised look at semaglutide specifically in non-diabetic CKD with obesity, and a 52% reduction in albuminuria is not a marginal signal. I am genuinely impressed by the magnitude, while staying honest about what it is: 101 patients, 24 weeks, and a surrogate endpoint rather than a hard kidney outcome. The number that would change my practice is not albuminuria at six months but eGFR slope and kidney failure over years, and this trial cannot give me that. The obvious unanswered question is whether the effect is additive on top of an SGLT2 inhibitor, since that combination is where most of these patients should already be heading. Can I use this with my patients? Cautiously yes, as an adjunct in the obese proteinuric patient who is intolerant of or incompletely controlled on existing therapy, while I wait for the outcome trial this clearly deserves.
References
Apperloo EM, Gorriz JL, Soler MJ, et al. Semaglutide in patients with overweight or obesity and chronic kidney disease without diabetes: a randomized double-blind placebo-controlled clinical trial. Nat Med. 2025;31(1):278–285. doi:10.1038/s41591-024-03327-6