Tolerability and Short-term Effectiveness of Novel Antidiabetic Agents and Metformin in Liver Transplant Recipients with Type 2 Diabetes: Insights from the DiaBoLT2021 Study

Abstract

Background and Aim

Type 2 diabetes mellitus (T2DM) affects up to one-third of liver transplant recipients and is associated with increased morbidity and reduced graft and patient survival. Post-transplant diabetes mellitus (PTDM) may emerge de novo or represent a persistence of pre-existing T2DM. Its management is complex due to potential interactions with immunosuppressive therapy, and insulin is often continued despite suboptimal outcomes, owing to its perceived safety and simplicity. Notably, data on the safety and effectiveness of novel glucose-lowering agents and metformin in this population remain limited. This study aims to evaluate the short-term tolerability and metabolic impact of novel antidiabetic drugs (GLP-1 receptor agonists, DPP-4 inhibitors, SGLT2 inhibitors) and metformin in adult liver transplant recipients with pre-existing or post-transplant T2DM.

Methods

A monocentric, observational study (DiaBoLT2021) was conducted, including 132 adult recipients of liver transplantation with T2DM, followed from December 2021 to December 2024 at a Clinical Nutrition and Metabolism Unit. Data were extracted from electronic medical records and evaluated at 6-month follow-up. Study endpoints included: (1) treatment tolerability; (2) changes in HbA1c, weight/BMI, and insulin requirements.

Results

Metformin was prescribed in 126 out of 132 patients; 5 discontinued due to gastrointestinal side effects. Among GLP-1 receptor agonist users (n=55), 4 discontinued due to nausea or vomiting. SGLT2 inhibitors were prescribed in 52 patients, with 1 discontinuation due to a genitourinary infection. No discontinuations occurred with DPP-4 inhibitors. All adverse events were mild and promptly resolved after discontinuation. Importantly, gastrointestinal side effects did not require any modification of immunosuppressive regimens. At 6 months, significant improvements in glycemic control and body weight were observed (p<0.05). Insulin therapy was discontinued in 28% of patients, while others reduced dosage or transitioned to simpler regimens.

Conclusions

In liver transplant recipients with T2DM, both metformin and novel antidiabetic agents appear safe and metabolically effective in the short term. These findings support a paradigm shift toward a safer and more personalized management of diabetes in this population, with the potential to reduce insulin burden, enhance metabolic outcomes, and harness the cardio-renal protective benefits offered by selected novel therapies.