Publication of the Week - 05/31/2024


Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes


Vlado Perkovic, M.B., B.S., Ph.D., Katherine R. Tuttle, M.D., Peter Rossing, M.D., D.M.Sc., Kenneth W. Mahaffey, M.D., Johannes F.E. Mann, M.D., George Bakris, M.D., Florian M.M. Baeres, M.D., Thomas Idorn, M.D., Ph.D., Heidrun Bosch-Traberg, M.D., Nanna Leonora Lausvig, M.Sc., and Richard Pratley, M.D.


The Journal of New England Medicine

Foreword for interim Chair: Dr. Salim Hayek

The FLOW study, a pivotal trial in the management of chronic kidney disease (CKD) in type 2 diabetes (T2D) patients, showed that semaglutide significantly reduces kidney disease progression and related mortality by 24%. This practice-changing result, achieved in a large international cohort, that adds semaglutide and likely other GLP1 receptor antagonists to our armamentarium for treating CKD.


BACKGROUND: Patients with type 2 diabetes and chronic kidney disease are at high risk for kidney failure, cardiovascular events, and death. Whether treatment with semaglutide would mitigate these risks is unknown.

Methods: We randomly assigned patients with type 2 diabetes and chronic kidney disease (defined by an estimated glomerular filtration rate [eGFR] of 50 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio [with albumin measured in milligrams and creatinine measured in grams] of >300 and <5000 or an eGFR of 25 to <50 ml per minute per 1.73 m2 and a urinary albumin-to-creatinine ratio of >100 and <5000) to receive subcutaneous semaglutide at a dose of 1.0 mg weekly or placebo. The primary outcome was major kidney disease events, a composite of the onset of kidney failure (dialysis, transplantation, or an eGFR of <15 ml per minute per 1.73 m2), at least a 50% reduction in the eGFR from baseline, or death from kidney-related or cardiovascular causes. Prespecified confirmatory secondary outcomes were tested hierarchically.

Methods:RESULTS: Among the 3533 participants who underwent randomization (1767 in the semaglutide group and 1766 in the placebo group), median follow-up was 3.4 years, after early trial cessation was recommended at a prespecified interim analysis. The risk of a primary-outcome event was 24% lower in the semaglutide group than in the placebo group (331 vs. 410 first events; hazard ratio, 0.76; 95% confidence interval [CI], 0.66 to 0.88; P=0.0003). Results were similar for a composite of the kidney-specific components of the primary outcome (hazard ratio, 0.79; 95% CI, 0.66 to 0.94) and for death from cardiovascular causes (hazard ratio, 0.71; 95% CI, 0.56 to 0.89). The results for all confirmatory secondary outcomes favored semaglutide: the mean annual eGFR slope was less steep (indicating a slower decrease) by 1.16 ml per minute per 1.73 m2 in the semaglutide group (P<0.001), the risk of major cardiovascular events 18% lower (hazard ratio, 0.82; 95% CI, 0.68 to 0.98; P=0.029), and the risk of death from any cause 20% lower (hazard ratio, 0.80; 95% CI, 0.67 to 0.95, P=0.01). Serious adverse events were reported in a lower percentage of participants in the semaglutide group than in the placebo group (49.6% vs. 53.8%).

Conclusions: Semaglutide reduced the risk of clinically important kidney outcomes and death from cardiovascular causes in patients with type 2 diabetes and chronic kidney disease. (Funded by Novo Nordisk; FLOW number, NCT03819153.)