#6653 USE OF GLUCAGON-LIKE PEPTIDE 1 RECEPTOR AGONISTS IN KIDNEY TRANSPLANT PATIENTS: A MULTI-CENTER STUDY
Authors: Sánchez Luis Alberto Vigara , Fernández Florentino Villanego , Orellana Cristhian , Alonso Myriam Eady , Márquez Maria Gabriela Sánchez , Jiménez María Belén García , Alonso Marta , Amaro Jose Manuel , Garcia Teresa , Mazuecos Auxiliadora 
Published: June 2023

Abstract

Background and Aims
Diabetes mellitus (DM) is a frequent complication in kidney transplant (KT) patients, leading to a higher cardiovascular mortality and graft loss. The use of therapies such as Glucagon-like peptide-1 receptor agonist (GLP-1RA) could have benefits in KT, although the experience reported so far is limited. The aim 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 in three Spanish hospitals (Puerta del Mar University Hospital, Jerez de la Frontera University Hospital and Puerto Real University Hospital) from February 2016 to July 2022. All patients had a minimum follow-up of 6 months after starting the treatment. 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. Parametric and non-parametric tests were performed according to the normality of the sample.

Results
In this period, 102 KT with DM were treated with GLP-1RA from 19/02/2016 to 22/07/2022. At the time of the prescription mean body mass index was 35.8 kg/m2 and the mean weight was 95 kg. Forty-two (44%) had developed post-transplant diabetes mellitus (PTDM). The mean age was 62 years and 56% were men. Mean baseline estimated glomerular filtration rate (eGFR) was 47.2 ml min/1.73 m2 and the time post-KT was 47 months. The GLP-1RA mostly prescribed was semaglutide (66.7%). Fifty-five (55%) patients reached the maximum recommended dose of the drug. The maintenance immunosuppressive therapy used was steroids (94.7%), tacrolimus (97.4%), mycophenolate (94.7%) and everolimus (2.6%). Eighty-four KT recipients had a minimum follow-up of 6 months and sixty-four were followed for 12 months. We observed stability in eGFR and a reduction in proteinuria (−19.1 mg/g at 6 months, p = .000 and −46.6 mg/g at 12 months, p = .000) during all the follow-up. Additionally, we found a significant reduction in systolic blood pressure (−7.5 mmHg at 6 months, p = .013 and −7,3 mmHg at 12 months, p = .004) despite the number of patients receiving angiotensin receptor blockers, angiotensin-converting enzyme and other antihypertensive therapies. Besides, their doses did not change during the period of the study. In our cohort, body weight significantly reduced (−3.6 Kg at 6 months, p = .000 and −3.6 Kg at 12 months, p = .000). Furthermore, HbA1c decreased (−1.2 mmol/L at 6 months, p = .000 and −1.5 mmol/L at 12 months, p = .000). Notably, insulin dose was also reduced (−2.2 UI/day at 6 months, p = 0.048) but the number of patients with sodium-glucose cotransporter 2 inhibitors increased at 12 months (p = 0.031). Finally, we observed a reduction in total cholesterol (−11.5 mg/dL at 6 months, p = .001 and −15.6 mg/dL at 12 months p = .000) and LDL-c (−9.2 mg/dL at 6 months, p = 0.002 and −16.8 mg/dL at 12 months, p = .000) during the follow-up. However, patients receiving statins and steroids and the dose remained unchanged. Fifteen patients (14.7%) suffered from side effects, mainly nausea and vomiting, and ten patients (9.8%) discontinued the treatment for this reason. No changes in the mycophenolate formulation were made. 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 were notified.

Conclusion
This is the first multicenter study that reports the effectiveness and safety of GLP-1RA in KT patients. 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.