TOPLINE:

For patients undergoing kidney dialysis, the use of GLP-1 receptor agonist semaglutide showed safety, with no significant increase in serious cardiovascular adverse events or mortality. The findings were especially important in the dialysis population, which had a low median survival of just 48 months, primarily driven by cardiovascular complications. Furthermore, with patients on dialysis typically excluded from outcomes trials, the study represented the largest prospective cohort of individuals treated with dialysis and an incretin therapy. 

METHODOLOGY:

• For the patient-level pooled analysis, researchers evaluated adverse event data of 34,064 participants in four key randomized cardiovascular or kidney outcomes trials involving GLP-1s — SUSTAIN-6, SELECT, FLOW, and SOUL. With the exception of SELECT, inclusion criteria included a diagnosis of type 2 diabetes for the trials.
• In all trials, participants were randomized to semaglutide or placebo at the beginning of the study.
• Among all patients, 307 (0.9%) initiated dialysis during the trial, including 141 who were randomized to semaglutide and 166 who received a placebo.
• Of those, 71 (50%) of 141 on semaglutide and 94 (56%) of 166 on placebo continued to receive the study medication after the start of dialysis, and the study results specifically refer to those patients.
• The study focused on serious adverse events, adverse events that led to permanent treatment discontinuation, and major cardiovascular adverse events (MACE).
• Patient characteristics were similar in the two groups, with an average age of the semaglutide and no semaglutide groups was 64.4 and 65.1 years, respectively. Approximately 74% were men.

TAKEAWAY:

• With a mean follow-up of 1.15 years from the day of dialysis initiation in both groups, there were no significant differences between the semaglutide and the placebo groups in any of the serious adverse events, including cardiac disorders, infections and infestations, gastrointestinal disorders, or adverse events leading to permanent discontinuation.
• There were also no significant differences in terms of MACE or all-cause mortality; in fact, the MACE event rate was numerically lower, at 9.7 per 100 person-years with semaglutide vs 16.1 with placebo.
• Likewise, the all-cause mortality rate was 13.8 per 100 person-years with semaglutide vs 18.1 with placebo.
• Hypoglycemia was similar between the groups.

IN PRACTICE:

“I think we can convincingly say that treatment with semaglutide was not associated with a higher proportion of serious adverse events, including MACE and all-cause mortality among those initiating dialysis,” said first author Klara R. Klein, MD, PhD, The University of North Carolina at Chapel Hill.

“Additionally, we noted a potential for cardiovascular and mortality benefit with semaglutide, necessitating further study of the potential of these agents to improve meaningful outcomes in people treated with dialysis.”

SOURCE:

This study was presented at the European Association for the Study of Diabetes (EASD) 2025 Annual Meeting in Vienna, Austria.

LIMITATIONS:

Patients were not randomized at the start of dialysis, and with the known benefits of semaglutide on MACE, all-cause mortality, and progression to dialysis among people with chronic kidney disease, “ semaglutide used prior to dialysis start may bias the cohort in ways that we cannot fully ascertain,” Klein said. In addition, differences in the collection of adverse events in the separate trials could prevent comparison of all adverse events across trials, Klein noted.

DISCLOSURES:

This study received funding from Novo Nordisk A/S. Klein’s disclosures included consulting or other relationships with Novo Nordisk A/S, Roche Pharmaceuticals, NCATS, Bayer, Boehringer Ingelheim, Carmot, Diasome, Gentibio, Eli Lilly, Rhythm Pharmaceuticals, and vTv Therapeutics.