Summary: In adults with type 2 diabetes and chronic kidney disease on stable ACE inhibitor or ARB therapy, semaglutide 1.0 mg once weekly reduced the primary composite kidney outcome by 24%, all-cause mortality by 20%, and major cardiovascular events by 18% compared with placebo, with fewer serious adverse events. The trial was stopped early for efficacy.
PICO Summary
| Element | Detail |
|---|---|
| Population | Adults with type 2 diabetes and CKD (eGFR 25–75 ml/min/1.73 m², UACR >100–5,000 mg/g) on stable ACEi/ARB (n=3,533). |
| Intervention | Semaglutide 1.0 mg subcutaneous weekly for a median of 3.4 years. |
| Comparison | Matching placebo weekly for the same duration. |
| Outcome | Primary kidney composite reduced 24% (HR 0.76; 0.66–0.88; P=0.0003). All-cause mortality -20% (HR 0.80). Major cardiovascular events -18% (HR 0.82). Cardiovascular death -29% (HR 0.71). Fewer serious adverse events. Trial stopped early for efficacy. |
FLOW: Semaglutide and Kidney Outcomes
RCT · T2D with CKD · median 3.4 years
Semaglutide 1.0 mg weekly cut major kidney events by 24% and reduced all-cause mortality and cardiovascular events in albuminuric T2D-CKD on RAS blockade. The trial stopped early for efficacy.
Expert Commentary
For years the nephroprotection conversation in type 2 diabetes has belonged almost entirely to the SGLT2 inhibitors, and I have been adding them to RAS blockade and feeling reasonably complete about it. FLOW is the trial that makes me stop and widen the lens. A 24% reduction in major kidney events, a mortality signal, and a cardiovascular death reduction in an albuminuric CKD population is not a soft result, and the early stopping reflects a genuine efficacy signal rather than statistical luck. What I find most useful clinically is that this was the 1.0 mg diabetes dose, not the higher obesity dose, so the kidney benefit sits within a regimen I already prescribe. The obvious question I am left with is whether the effect is additive on top of an SGLT2 inhibitor, because the trial was not built to answer that, and most of my CKD patients are or should be on both drug classes. Can I use this with my patients? Yes, and I suspect I will, particularly in the albuminuric patient who cannot tolerate or has already maxed out their SGLT2 inhibitor. Read this one before your next CKD clinic.
References
Perkovic V, Tuttle KR, Rossing P, et al. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. N Engl J Med. 2024;391(2):109–121. doi:10.1056/NEJMoa2403347