medwireNews: Glucagon-like peptide (GLP)-1 receptor agonist use is associated with a significantly decreased risk for graft loss and mortality among kidney transplant recipients with type 2 diabetes, US study findings indicate.
Writing in The Lancet Diabetes & Endocrinology, Babak Orandi (New York University, USA) and colleagues explain that people who have undergone transplantation are routinely excluded from clinical trials, “creating a knowledge gap for the 250,000 kidney transplant recipients in the USA and many more around the world.”
They say that their results “are the strongest to date supporting GLP-1 receptor agonist use in kidney transplant recipients with diabetes,” but caution that the “benefits must be balanced with the risk of diabetic retinopathy.”
Orandi and team used data from the US Renal Data System and Medicare to identify 18,016 individuals with type 2 diabetes who underwent a first-time kidney transplantation between 2013 and 2020. Of these, 1969 (10.9%) had at least one prescription for a GLP-1 receptor agonist post-transplantation, most commonly dulaglutide. The median time from transplantation to GLP-1 receptor agonist initiation was 19 months and, over a median 503 subsequent days of follow-up, the median duration of use was 254 days.
In unadjusted analyses, the 5-year cumulative incidence of graft loss, excluding patients who died with a functioning kidney, was significantly lower among GLP-1 receptor agonist users than among nonusers, at 7.5% versus 12.2%. The 5-year unadjusted cumulative incidence of mortality was also significantly lower with GLP-1 receptor agonist use than without it, at 13.5% versus 19.9%.
In a cohort matched for post-kidney transplantation survival time, the unadjusted 5-year cumulative incidence of graft loss remained significantly lower among GLP-1 receptor agonist users versus nonusers (6.0 vs 10.7%).
Mortality rates were also significantly lower when patients were matched for survival time before GLP-1 receptor agonist initiation, at 17.0% for users and 25.8% for nonusers.
And after adjustment for potential confounders including, sex, age, race/ethnicity, BMI, Medicaid eligibility, cause of kidney failure, post-transplantation insulin use, and comorbidity, Orandi et al found that GLP-1 receptor agonist use was associated with a significant 49% lower incidence of death-censored graft loss and a significant 31% lower incidence of mortality compared with no use.
In terms of safety, GLP-1 receptor agonist use was not associated with an increased risk for key endpoints such as pancreatitis, biliary complications, or medullary thyroid cancer, but users had a significant 49% higher risk for diabetic retinopathy than nonusers in adjusted analyses.
Orandi et al describe the study as “the largest to investigate the outcomes of GLP-1 receptor agonist use in kidney transplant recipients with pre-existing diabetes in the USA.”
They conclude: “These real-world findings, in addition to smaller reports, offer important preliminary guidance on the potential benefits and safety of GLP-1 receptor agonists in a population that has not been studied in a clinical trial setting.”
The authors add that, in terms of the risk for diabetic retinopathy, “[t]he risk-benefit ratio might be enhanced by multidisciplinary diabetes treatment with emphasis on eye surveillance.”
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Lancet Diabetes Endocrinol 2025; doi:10.1016/S2213-8587(24)00371-1
