Impact of GLP1-receptor agonists on diabetes after liver transplantation - A single-center experience.

Background

Metabolic syndrome can be observed in nearly 50% of patients undergoing liver transplantation (LT), determining a higher risk for cardiovascular disease and accelerated graft damage. One or more of its components (obesity, insulin resistance or diabetes, hypertension and dyslipidemia) may be already present at the time of LT or may develop in the post-transplant setting, contributing to the recurrence or de novo development of metabolic dysfunction-associated steatotic liver disease (MASLD). Post-transplant MASLD can be observed in up to 50% of patients 1 year after LT. Immunosuppression related side effects play a non-negligible role in the development of insulin resistance, diabetes, hypertension, dyslipidemia and weight gain in the post-transplant setting. Nearly 30% of liver transplant recipients develop new-onset diabetes mellitus after LT and up to 40% of LT recipients are obese 3 years after LT. It seems therefore of pivotal importance the need for an early intervention in the management of the above-mentioned risk factors, to reduce recurrence or de novo development of metabolic syndrome and MASLD, cardiovascular risk and graft damage.GLP-1 receptor agonists (GLP1-RAs) therapy has achieved optimal results in the treatment of adults with type 2 diabetes in terms of reduction of HbA1c and weight, with only mild to moderate adverse effects (mainly nausea, diarrhea, vomiting, abdominal discomfort). They have also been approved for reducing the risk of cardiovascular events in patients with diabetes and cardiovascular disease. A reduction in body weight has also been observed in overweight and obese individuals without diabetes. Following these results, some small retrospective studies have been performed in LTR with diabetes, showing the efficacy of GLP-1RAs in achieving better glycemic control and a reduction in body weight. AIMOur study aimed to assess the efficacy and safety of weekly GLP1-RAs injection in a cohort of LTR with diabetes.

Material and Methods

We retrospectively evaluated, between 2014 and 2023, all patients who underwent LT at our center and were treated with a GLP1-RA (semaglutide, liraglutide or dulaglutide) for diabetes. Body weight, body mass index, Hb1Ac values, ALT and AST values, adverse events and drug discontinuation were recorded at each follow-up visit. Results were expressed as mean ± SD, paired t-test was used when needed.

Results

A total of 24 patients were included in the study. The characteristics of our population are shown in Table 1. The mean age was 59.0 (± 6.76) years, 29,2% were female. Alcohol was the main etiology of cirrhosis, and 13 patients had HCC.As shown in Table 2, after 6 months of treatment, there was a significant reduction in body weight and BMI (88.1 ± 17.7, p = 0.015; 29.1 ± 4.6, p = 0.026, respectively). The reduction was even more pronounced after 12 months (84.6 ± 16.7, p = 0.003; 28.4 ± 4.4, p = 0.011, respectively). A reduction in HbA1c values and transaminases levels was also observed, although without statistical significance. No major effects were recorded; only one patient (4%) experienced persistent nausea leading to therapy discontinuation. No adjustment in immunosuppression dosages was needed.

Conclusions

In this single-center retrospective analysis, we showed that, in LTR with diabetes, weekly GLP1-RAs therapy is safe and induces early and relevant weight loss after six and twelve months of treatment. Larger multicenter studies with longer follow-up are needed to assess sustained weight loss, long-term graft outcomes, and the potential role of GLP1-RAs in reducing cardiovascular risk in LTR.