GLP-1 RAs Show Benefit for Kidney Transplant Recipients with Diabetes

GLP-1 receptor agonists (GLP-1 RAs) may be a promising treatment option for kidney transplant recipients with diabetes, according to findings from a recent study.1

Leveraging data from the US Renal Data System (USRDS) for more than 18,000 kidney transplant recipients with type 2 diabetes at transplantation and Medicare as their primary insurance, the study found use of GLP-1 RAs was associated with a significantly reduced risk of graft loss and mortality but an increased risk of diabetic retinopathy.1

The recent rise of GLP-1 RAs has been nothing short of revolutionary for the field of medicine, with no other class of medications matching their profound impact across multiple disciplines. Most recently, Novo Nordisk’s semaglutide (Ozempic) earned FDA approval for reducing the risk of kidney disease worsening, kidney failure, and death due to cardiovascular disease in adults with type 2 diabetes and CKD.2

“Given their cardiometabolic and renal benefits, GLP-1 receptor agonists might be advantageous for kidney transplant recipients with diabetes, especially in light of the need for chronic immunosuppression; however, trials are few and safety concerns exist,” Babak Orandi MD, PhD, an associate professor of surgery and medicine at NYU Langone, and colleagues wrote.1

To evaluate the outcomes and safety of GLP-1 RAs in kidney transplant recipients with pre-existing type 2 diabetes, investigators conducted a US-based retrospective cohort study using data from the USRDS, which maintains data on all kidney failure patients and kidney transplant recipients in the US and integrates data from the Organ Procurement and Transplantation Network, the Centers for Medicare and Medicaid Services, and Medicare claims data, including prescription drug claims.1

Between January 2013 and December 2020, investigators identified 44,536 first-time kidney transplant recipients with Medicare as primary payer in the 6 months before and at transplantation. Of note, 24,192 patients were excluded because they did not have type 2 diabetes, and 2328 patients were ineligible due to missing values and use of GLP-1 RAs prior to transplantation.1

In total, the primary cohort included 18,016 kidney transplant recipients with diabetes. Of these patients, 1969 (10.9%) had ≥ 1 GLP-1 RA prescription filled post-transplant.1

Investigators noted GLP-1 RA users were younger (57 years of age vs 60 years of age; P<.0001) and more likely to be female (39.9% vs 35.2%; P <.0001) than GLP-1 RA non-users. Among GLP-1 rRA users, 28.0% were non-Hispanic White, 35.7% were non-Hispanic Black, and 28.8% were Hispanic.1

Upon analysis, the 5-year unadjusted cumulative incidence of death-censored graft loss from a cohort matched on survival time before GLP-1 RA initiation was 6.0% for GLP-1 RA users and 10.7% for non-users (Gray's test P =.004).1

Additionally, the 5-year unadjusted cumulative incidence for mortality from a cohort matched on survival time before GLP-1 RA initiation was 17.0% for GLP-1 RA users and 25.8% for non-users (log-rank P = .0006). The 5-year unadjusted cumulative incidence for mortality was 13.5% for GLP-1 RA users and 19.9% for non-users (log-rank P <.0001).1

Further analysis revealed GLP-1 RA use was associated with a 49% reduced incidence of death-censored graft loss (adjusted subhazard ratio [aSHR], 0.51; 95% CI, 0.36–0.71; P = .0001) and 31% lower mortality (adjusted hazard ratio [aHR], 0.69; 95% CI, 0.55–0.86; P = .001).1

Investigators pointed out inferences were robust when matched on survival time:

• Death-censored graft loss aSHR, 0.53; 95% CI, 0.37–0.75; P = .0005
• Mortality aHR, 0.70; 95% CI, 0.55–0.88; P = .003

Additionally, they noted safety endpoints were rare and not associated with GLP-1 RAs, except for diabetic retinopathy (aHR, 1.49; 95% CI, 1.11–2.00; P = .008).1

“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,” investigators concluded.1

References

1. Orandi BJ, Chen Y, Li Y, et al. GLP-1 receptor agonists in kidney transplant recipients with pre-existing diabetes: a retrospective cohort study. The Lancet Diabetes & Endocrinology. https://doi.org/10.1016/S2213-8587(24)00371-1

2. Brooks A. FDA Approves Semaglutide (Ozempic) for Type 2 Diabetes, Chronic Kidney Disease. HCPLive. January 28, 2025. Accessed March 6, 2025. https://www.hcplive.com/view/fda-approves-semaglutide-ozempic-type-2-diabetes-chronic-kidney-disease