The Use of GLP1R Agonists for the Treatment of Type 2 Diabetes in Kidney Transplant Recipients

Abstract

Background. Glucagon-like peptide-1 receptor agonists (GLP1RA) have been shown to improve glucose control and diabetes-related comorbidities in patients without solid organ transplants. The effectiveness, safety, and tolerability of GLP1RA after kidney transplantation have not been adequately studied. Methods. We retrospectively reviewed data on kidney transplant recipients performed in our institution, who were initiated on GLP1RA either for the treatment of type 2 diabetes diagnosed before transplantation or posttransplant diabetes. We analyzed efficacy, safety, and the effect on kidney allograft function. Results. Seventeen kidney transplant recipients were initiated on GLP1RA therapy, 14 of which remained on the medication for at least 12 months. The use of GLP1RA had no significant impact on weight loss, but was associated with a significant reduction in the total daily insulin dose, from the median of 63 [interquartile range 43-113] IU to 44 [interquartile range 25-88] and reduction in the risk of hypoglycemia in patients who were on therapy for at least approximately 12 months. Kidney function remained stable and none of the recipients experienced acute rejection. Tacrolimus dose was not significantly changed. Five patients (29%) discontinued GLP1RA therapy—4 due to side effects and 1 due to uncontrolled hyperglycemia. Conclusions. GLP1RA may be a relatively safe and effective treatment for kidney transplant recipients with type 2 diabetes that allows for a reduction in insulin requirements. More studies are needed to determine whether the use of these agents will translate into an improvement in allograft and patient survival.

Management of post‐transplant diabetes: immunosuppression, early prevention, and novel antidiabetics

“…These studies show that SGLT2is can potentially be used in post‐transplant diabetes, but the patients should undergo close monitoring. In the case of the GLP1‐RAs, only retrospective case reports for PTDM patients are available [124‐128,130], wherein no serious safety concerns have arisen so far. Eight years after the initial call for clinical trials on PTDM treatment, it is therefore once again “time to collaborate” [147].…”

“…Compared to SGLT2is, the clinical experience of GLP1‐RAs in PTDM is entirely limited to case series and retrospective studies [124‐129]. The largest study, from Singh and colleagues, investigated the use of dulaglutide in 63 solid organ transplant recipients with diabetes (of whom 20 had PTDM compared to 43 with pre‐existing type 2 diabetes) [126].…”

“…HbA1c reduction with GLP1‐RAs, when compared to the SGLT2is, does not depend on kidney function and has been clinically meaningful (from 10.0% to 8.1% in average) in 7 diabetic patients with poor glycemic control [125] (this study unfortunately did not explicitly state that these were PTDM patients, as opposed to T2DM patients after kidney transplantation). However, weight reduction was observed in all of these studies [124‐129] (Kukla et al reporting a nonsignificant P ‐value of 0.2 [128]).…”

Dulaglutide as an Effective Replacement for Prandial Insulin in Kidney Transplant Recipients with Type 2 Diabetes Mellitus: A Retrospective Review

“…In a previous study on solid organ transplant recipients with diabetes, dulaglutide exhibited positive results for reducing body weight and insulin dose [ 11 ]. Furthermore, GLP-1RA decreased insulin dose and hypoglycemia risk in KT recipients [ 12 ]. Our results are consistent with these studies and support the use of dulaglutide for glycemic control in KT recipients.…”

Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter 2 inhibitors for diabetes after solid organ transplantation

“…No episodes of acute rejection were reported. Four (24%) patients discontinued the drugs due to side effects, which included an episode of acute pancreatitis and an additional patient because of poor glycemic control [85].…”