GLP-1 Drugs Linked to Improved Survival After Liver Transplant

Liver transplant patients who took a GLP-1 receptor agonist had a lower risk of death than those who weren’t on a GLP-1 drug, according to a retrospective three-center cohort study.
Among 2,402 patients, those on GLP-1 receptor agonists after their transplant were 45% less likely to die over a median 3.9 years of follow-up (adjusted HR 0.55, 95% CI 0.38-0.80, P=0.002). That mortality risk advantage held whether or not transplant patients had type 2 diabetes, though the protective effect was greater among those without diabetes.
A replication cohort of 1,443 liver transplant recipients drawn from a U.S. claims database mirrored those results, showing 45% and 55% lower post-transplant mortality risks linked with GLP-1 use in two analyses (aHRs 0.55 and 0.45), reported Zhihao Li, MD, of the Mayo Clinic in Rochester, Minnesota, at the American Association for the Study of Liver Diseases annual Liver Meeting in Denver.
“Several points support a real effect here,” Li said in a presentation at the meeting. “The results were replicated in an independent cohort, they’re similar to what’s been reported in other organ transplants, and there are plausible cardiovascular and anti-cancer pathways.”
Metabolic dysfunction-associated steatotic liver disease (MASLD) is on pace to become the leading cause of liver transplant in the U.S. While a transplant cures liver disease, it doesn’t remove a patient’s metabolic or metabolic-related risks, Li noted. GLP-1 drugs deliver cardiometabolic and kidney benefits for patients with liver disease, but their value among liver transplant patients isn’t clear, he added.
The primary study cohort included adults who underwent a liver transplant between 2015 and 2025 at one of three Mayo Clinic sites. Patients’ transplant indication was either metabolic dysfunction-associated steatohepatitis (MASH) or another etiology with type 2 diabetes or a body mass index (BMI) of at least 30 kg/m². The replication cohorts were drawn from claims data in the OptumLabs Data Warehouse.
Median patient age was 61.2 years, 65.4% were male, 77.5% were white, and the median Model for End-Stage Liver Disease (MELD)-Na score was 20. More than one-third (35.5%) had a MASH or metabolic indication for liver transplant. All patients had metabolic risk factors before liver transplant. Most patients had type 2 diabetes (58.9%), hypertension (65.3%), or a BMI of at least 30 (64.8%).

Among the 841 transplant patients who took GLP-1 drugs, 72% started them after their transplants. Median time to first GLP-1 dose was 1.5 years after transplant, and the median time spent taking the drugs was 1.2 years. Those on GLP-1 drugs were more likely to have MASH, diabetes, hypertension, obesity, or to be on statin therapy.
GLP-1 drug use was associated with a 14.2% drop in LDL cholesterol, an 8.3% drop in total cholesterol, and a 2.6% decline in HbA1c. Body weight fell by 5% in the 2 years after patients started a GLP-1 agonist.
Despite those changes, the reasons for the lower mortality risks weren’t clear, Li said. Those on GLP-1 drugs weren’t significantly less likely than their non-GLP-1 drug counterparts to experience a major adverse cardiovascular event (aHR 1.03, 95% CI 0.56-1.92) or, specifically, myocardial infarction (aHR 0.78, 95% CI 0.29-2.09).
The same was true for major adverse kidney events, sustained estimated glomerular filtration rate decline of at least 40%, or kidney transplant after liver transplant, though trends favored use of GLP-1 drugs. Li noted that a possible signal emerged for kidney failure in favor of GLP-1 drugs, but the difference just missed significance (aHR 0.46, P=0.06).
Most people who die after a liver transplant have a functioning graft, Li noted. Instead, malignancies, cardiovascular events, infections, and renal failure account for the majority of post-transplant deaths. Transplant patients on GLP-1 drugs were less likely than nonusers to die from those non-liver causes, including cardiovascular and cerebrovascular events, malignancies, infections, or graft failure. “This helps explain the survival benefit we observed,” he said.
Limitations included the study’s lack of power to detect differences in major adverse cardiovascular or kidney events. The cause of death wasn’t known in 23% of patients, and drug exposure was relatively short. Sicker transplant recipients started GLP-1 drugs less often, Li noted.