GLP-1 drugs may extend life, graft survival for kidney transplant recipients with diabetes
Key takeaways:
- Kidney transplant recipients with type 2 diabetes prescribed GLP-1 receptor agonists had 31% lower mortality vs. nonusers.
- GLP-1 receptor agonist use was associated with 49% lower incidence of graft loss.
For kidney transplant recipients with type 2 diabetes, use of glucagon-like peptide-1 receptor agonists was associated with improved long-term graft survival and overall survival, according to study data.
In a retrospective cohort study, Babak J. Orandi, MD, PhD, associate professor in the departments of surgery and medicine at NYU Grossman School of Medicine and NYU Langone Health, and colleagues analyzed data from 18,016 U.S. kidney transplant recipients with type 2 diabetes at transplantation from 2013 to 2020. They compared data from the 1,969 recipients who filled at least one prescription for a GLP-1 receptor agonist after transplant with data from those without a GLP-1 drug prescription. All transplant recipients had Medicare as their primary insurance, and data were derived from the U.S. Renal Data System.
The researchers observed more women among the GLP-1 drug users (39.9% vs. 35.2%); users were significantly younger at transplant than nonusers (median age, 57 years vs. 60 years) and had significantly higher BMI (31.2 km/m2 vs. 29.6 km/m2). Use of GLP-1 drugs increased during the study period — with 10.1% of transplant recipients with type 2 diabetes filling at least one prescription in 2013, 13.4% in 2017 and 12% in 2018 — until the COVID-19 pandemic, with 5.6% filling a prescription in 2020. Among the cohort, 49% were prescribed dulaglutide (Trulicity, Eli Lilly) in 2020, which was the most prescribed GLP-1 receptor agonist during the study, according to researchers.
At 5 years of follow-up, significantly fewer GLP-1 drug users (7.5%) than nonusers (12.2%) experienced death-censored graft loss, for a 49% lower risk for graft loss with GLP-1 drug use when adjusted for insulin use (adjusted subhazard ratio [aSHR] = 0.51; 95% CI, 0.36-0.71).
In addition, at 5 years, significantly fewer GLP-1 drug users (13.5%) than nonusers (19.9%) had died, for a 31% lower mortality risk with GLP-1 drug use (aSHR = 0.69; 95% CI, 0.55-0.86).
Results were not different when adjusted for BMI. Results were similar when data from GLP-1 drug users were matched with a cohort of living nonusers who had similar posttransplant survival time and a functioning graft.
About 25% of the effects of GLP-1 drugs on the kidney are likely attributable to blood pressure and glucose improvements, Orandi told Healio.
“That being said, there are other aspects of the medications that seem to have other effects that are independent of weight loss, independent of blood glucose lowering, that I do not think we still fully have an answer to,” he said. “An interesting next phase is to try to understand how we get these benefits, because maybe there are ways to further exploit that benefit for even better long-term improvements in graft and patient survival.”
Severe adverse events were “rare,” according to the researchers. However, risk for diabetic retinopathy was significantly higher among the GLP-1 drugs users than nonusers (aHR = 1.49; 95% CI, 1.11-2), which Orandi said is a result of rapidly lowered blood glucose and not a class effect of GLP-1 receptor agonists.
Future studies should include newer GLP-1 receptor agonists and combinations, Orandi said.
“There are a couple of years of lag time from when the data are generated through clinical care and when we actually have them available to study,” he said. “The most commonly used drug in this study was dulaglutide. Since then, we have come a long way, and the next generation of medications is even more effective for weight loss, even more effective for diabetes management. It may be that we have even more of a benefit with the medications we [now] have available.”
For more information:
Babak J. Orandi, MD, PhD, can be reached at babak.orandi@nyulangone.org.
Collapse