MO637: Effectiveness and Safety of Glucagon-Like Peptide-1 Receptor Agonist in a Cohort of Kidney Transplant Recipients
Authors: Alberto Vigara Luis , Villanego Florentino , Orellana Cristhian , Naranjo Muñoz Javier , Garcia Teresa , Mazuecos Auxiliadora 
Published: May 2022

Abstract

BACKGROUND AND AIMS
Diabetes mellitus (DM) is a complication in kidney transplant (KT). Therapies such as glucagon-like peptide-1 receptor agonist analogs (GLP-1RA) have been incorporated that could have benefits in KT, although experience is limited [1, 2]. The objective of our study is to describe the effectiveness and safety of GLP-1RA in KT patients.

METHOD
Retrospective cohort study of KT with DM who started GLP-1RA between February 2016 and December 2021. Clinical and demographic variables were analyzed. We collected GLP-1RA type and dose. Glomerular filtration rate (eGFR), proteinuria and weight were collected at the start of treatment and after 6 and 12 months. We analyze glycemic control, blood pressure and lipid profile. Acute rejections (AR), de novo donor-specific antibodies (DSA) and adverse effects were documented. A descriptive analysis was performed and the variables described before and after the start of treatment were compared. Parametric and non-parametric tests were performed according to the normality of the sample.

RESULTS
In this period, 50 KT with DM treated with GLP-1RA in our center from 1 March 2016 to 15 December 2021. Sixteen patients (32%) had developed post-transplant diabetes mellitus (PTDM). The mean age was 62.8 years and 52.5% were men. Mean baseline estimated glomerular filtration rate (eGFR) was 46.1 mL/min/1.73 m2 and the time post-KT was 38 months. The GLP-1RA mostly prescribed was semaglutide (47.5%), followed by liraglutide (32.5%) and dulaglutide (20%). Twenty-nine patients (58%) reached the maximum recommended dose of the drug. All patients received steroids, tacrolimus and mycophenolate. Forty KT recipients had a minimum follow-up of 6 months and 26 were followed for 12 months. Values of variables compared during the follow-up are shown in Table 1.
We observed an improvement in eGFR (+3.5 mL/min/1.73 m2 at 12 months, P = 0.030) and a reduction in proteinuria (−59.1 mg/g at 6 months, P = 0.009 and −48.5 mg/g at 12 months, P = 0.021) during all the follow-up. Additionally, we found a significant reduction in systolic blood pressure (−9.2 mmHg at 12 months, P = 0.022) despite the number of patients receiving angiotensin receptor blockers, angiotensin-converting enzyme and other antihypertensive therapies as well as their doses that did not change during the period of the study. In our cohort, body weight significantly reduced (−2.4 Kg at 6 months, P = 0.006 and −3 Kg at 12 months, P = 0.041). Furthermore, HbA1c decreased (−9 mmol/mol at 6 months, P &lt;0.001 and −5 mmol/mol at 12 months, P = 0.018). Notably, insulin dose was also reduced (−4 UI/day at 6 months, P = 0.003 and −4 UI/day at 12 months, P = 0.036) and the rest of antidiabetic treatment did not significantly change. Finally, we observed a reduction in total cholesterol (−14 mg/dL at 6 months, P = 0.015 and −6.3 mg/dL at 12 months, P = 0.344) and LDL-c (−8.8 mg/dL at 6 months, P = 0.49 and −4.9 mg/dL at 12 months, P = 0.384) during the follow-up.
Twelve patients (24%) suffered from side effects, mainly nausea and vomiting, and only two patients (4%) discontinued the treatment. One patient discontinued the treatment due to the diagnosis of pancreatic cancer 8 months after starting the drug.
We did not find differences in the levels or in the dose of tacrolimus. Neither AR episodes nor de novo DSAs’ development was notified.

CONCLUSION
In conclusion, this is one of the largest series reporting the effectiveness and safety of GLP-1RA in a cohort of KT. Our results support that it can be an option for the management of DM in these patients. Its use is safe and it does not seem to alter tacrolimus trough levels, to induce AR episodes or de novo DSAs development.