Clinical question: Does treatment with semaglutide in patients with type 2 diabetes and chronic kidney disease (CKD) prevent the progression of CKD or death from kidney and cardiovascular events?
Background: Patients with CKD are at high risk for kidney failure and death from cardiovascular events. Semaglutide, a glucagon-like peptide 1 (GLP-1) receptor agonist, has been shown to reduce cardiovascular events in patients with type 2 diabetes, but its effect on kidney outcomes is not fully understood.
Study design: Randomized, double-blinded, placebo-controlled trial
Setting: 28 countries, 387 sites
Synopsis: 3,533 patients with CKD and type 2 diabetes were randomly assigned to receive once-weekly semaglutide (1,767) or placebo (1,766). The trial had two primary endpoints: major kidney disease events (a composite of the onset of kidney failure with initiation of dialysis, kidney transplantation, eGFR of less than 15 mL/min/1.73 m2, or eGFR reduction of 50% from baseline) or death from renal and cardiovascular events. The trial was stopped early at a median follow-up of 3.4 years. Patients in the semaglutide arm had a 24% lower relative risk of a primary outcome event (331 versus 410 events, HR, 0.76; P=0.0003), with an NNT of 20 patients over three years to prevent one major primary outcome event. Results for kidney-specific components of the primary outcome (HR, 0.79) and death from cardiovascular causes (HR, 0.71) were similar. Limitations include underrepresented Black and indigenous populations and the inability of the trial to assess combination therapy with sodium-glucose cotransporter 2 inhibitors and nonsteroidal mineralocorticoid receptor antagonists.
Bottom line: In patients with type 2 diabetes and CKD, semaglutide reduced the risk of CKD progression and death from renal and cardiovascular events.
Citation: Perkovic V, 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.
Dr. Atencio is an assistant professor of medicine and co-chair of hospital medicine clinical operations at the University of California Davis School of Medicine, and president of SHM’s Sacramento chapter, both in Sacramento, Calif.