Semaglutide Decreases Risk of Kidney Failure, Worsening of Kidney Disease, and Kidney-Related or Cardiovascular Death
Clinical question: Does treatment with semaglutide in patients with chronic kidney disease (CKD) and diabetes mellitus (DM) type II reduce the risk of kidney failure, progression of chronic kidney disease, or kidney-related or cardiovascular death?
Background: Diabetes is the most common cause of CKD in many countries. Studies of renin-angiotensin inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated decreased risks of cardiovascular and renal-related outcomes but studies have yet to evaluate glucagon-like peptide (GLP-1) receptor agonists.
Study design: Double-blinded, randomized, placebo-controlled trial
Setting: Multinational (387 sites in 28 countries)
Synopsis: This study randomized 3,533 participants with DM type II and CKD to receive semaglutide at 1 mg weekly (1,767 participants) or placebo (1,766 participants) and followed participants over a median of 3.4 years. There was a 24% reduction (P=0.0003) of major kidney disease events in patients receiving semaglutide weekly (number needed to treat, 20). Kidney events were defined as dialysis, transplantation, estimated glomerular filtration rate of less than 15, at least 50% reduction in estimated glomerular filtration rate from baseline, or kidney-related or cardiovascular death. Secondary outcomes demonstrated reduced major cardiovascular events and slowed the progression of CKD in the semaglutide group. Adverse events and rates of discontinuation were similar in both groups. One limitation was that only 15% of patients were on SGLT2 inhibitors. For patients on an SGLT2 inhibitor, semaglutide showed a nonsignificant trend towards benefit in patients with DM for over 15 years and A1C lower than 8% but not higher.
Bottom line: Semaglutide at a dose of 1.0 mg weekly compared to placebo decreased the risk of kidney failure or progression and kidney-related or cardiovascular death in patients with CKD and type II DM.
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):109-21. doi: 10.1056/NEJMoa2403347.
Dr. Smith is an academic hospitalist in the section of hospital medicine at UPMC Presbyterian Hospital, and a clinical assistant professor of medicine at the University of Pittsburgh School of Medicine, both in Pittsburgh.