GLP1RAs in liver-transplanted people with diabetes: ad interim results of a 24 months trial

Introduction: GLP1 receptor agonists (GLP1RAs) are first line drugs for DM2, due to their effects on glycemic control, cardiorenal protection and weight-loss action. However, consistent data about efficacy and safety in patients with liver transplant (LT) are lacking. Aim: to assess the efficacy and safety of GLP1RAs in people with LT and diabetes in a period of 24 months. METHODS: 52 patients with DM and LT, were enrolled: follow-up visits were planned 6-12-24 months after starting a GLP1RA-based therapy (dulaglutide or injectable semaglutide), as add on to metformin or insulin. We assessed glycemic control, body weight and composition (with bio-impedance analysis), liver fibrosis and steatosis (with transient elastography). Amylase, lipase levels and concomitant therapies were recorded at all visits. Patients had an e-mail contact to report any adverse events (AE). At the ad interim analysis, all patients enrolled underwent the first follow-up visit, 29 patients completed the study. Results: We observed a decrease in blood glucose (BG – 8.0±2.2 to 6.8±1.45 to 7.4±1.7mmol/L) and HbA1c (7.1±0.9 to 6.5±1.0 to 6.4±0.6%), p<0.01. BMI, fat mass e fat free mass showed a slight, non significative, improvement. We found no changes in data from elastography. 3 patients interrupted the treatment due to major AE (2 had pancreatitis 8 and 12 month from baseline, 1 had an increase of lipase >3 times the normal values. Of them, all underwent repeated abdominal surgery in the past). At the short-term follow-up, we already observed the improvement in BG and HbA1c (p<0.01), amylase and lipase didn’t increase significantly. 14 people (26.9%) reported mild nausea, but only 3 patients (5.8%) reduced the drug dose. Among 30 patients requiring insulin at enrollment, 15 (50%) and 5 (16.6%), respectively, reduced or suspended insulin therapy in the first 6 months. Conclusions: GLP1RAs can be considered effective in patients with LT. Further studies are needed to assess if repeated abdominal surgery could be a potential contraindication to their use.