Summary: In patients with type 2 diabetes and chronic kidney disease, once-weekly semaglutide 1.0 mg reduced the risk of major kidney disease events and death from kidney-related or cardiovascular causes by 24 percent versus placebo (hazard ratio 0.76; 95 percent CI 0.66 to 0.88; P equals 0.0003). Slower eGFR decline, fewer major cardiovascular events, and lower all-cause mortality were also observed.
PICO Summary
| Element | Detail |
|---|---|
| Population | 3533 adults with type 2 diabetes and chronic kidney disease (eGFR 50 to 75 with urinary albumin-to-creatinine ratio above 300 to below 5000, or eGFR 25 to below 50 with ratio above 100 to below 5000); multinational, double-blind, placebo-controlled phase 3 randomised trial; median follow-up 3.4 years. |
| Intervention | Subcutaneous semaglutide 1.0 mg once weekly (n equals 1767). |
| Comparison | Matching placebo once weekly (n equals 1766). |
| Outcome | Primary composite of major kidney disease events: 331 vs 410 first events; HR 0.76 (95 percent CI 0.66 to 0.88; P equals 0.0003), a 24 percent relative reduction. Kidney-specific composite HR 0.79 (95 percent CI 0.66 to 0.94). Mean annual eGFR slope less steep by 1.16 ml/min/1.73m2 (P below 0.001). Major cardiovascular events HR 0.82 (95 percent CI 0.68 to 0.98; P equals 0.029). Death from any cause HR 0.80 (95 percent CI 0.67 to 0.95; P equals 0.01). Death from cardiovascular causes HR 0.71 (95 percent CI 0.56 to 0.89). Serious adverse events 49.6 percent vs 53.8 percent. |
FLOW: Semaglutide and Kidney Outcomes
RCT · T2D + CKD · 3.4 yr median
Once-weekly semaglutide cut major kidney disease events and death by 24 percent versus placebo in type 2 diabetes with CKD, with concordant cardiovascular and mortality benefits.
Expert Commentary
The verdict is that this large, double-blind, placebo-controlled phase 3 trial provides solid evidence that once-weekly semaglutide protects the kidney in type 2 diabetes with established chronic kidney disease. A 24 percent reduction in the primary composite, with a confidence interval well clear of unity and a low P value, is reinforced by concordant effects on the kidney-specific composite, eGFR slope, major cardiovascular events, cardiovascular death, and all-cause mortality. The serious adverse event rate was lower with semaglutide, which is reassuring for tolerability at this dose. One limitation deserves weight: the trial was stopped early at a prespecified interim analysis on the recommendation of the data monitoring committee, and trials halted early for benefit can overestimate the true effect size, so the point estimates may be read as an upper bound rather than a precise figure. The trial was funded by the manufacturer, Novo Nordisk, which warrants the usual caution about sponsorship even within a rigorous design. Can I use this with my patients? Yes, for the patient in front of you with type 2 diabetes, an eGFR roughly between 25 and 75, and meaningful albuminuria, semaglutide is a defensible addition to a statin, renin-angiotensin blockade, and where appropriate an SGLT2 inhibitor. Confirmation of durability beyond the truncated follow-up would be welcome.
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