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

Kukla, Aleksandra; Hill, Jennifer; Merzkani, Massini; Bentall, Andrew; Lorenz, Elizabeth C.; Park, Walter D.; D'Costa, Matthew R; Kudva, Yogish C.; Stegall, Mark D.; Shah, Pankaj

doi:10.1097/txd.0000000000000971

Cited by 37 publications

(35 citation statements)

References 42 publications

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“…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].…”

Section: Management Of Ptdm: Novel Antidiabeticsmentioning

confidence: 99%

“…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].…”

Section: Management Of Ptdm: Novel Antidiabeticsmentioning

confidence: 99%

“…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]).…”

Section: Management Of Ptdm: Novel Antidiabeticsmentioning

confidence: 99%

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

et al. 2020

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Summary Post‐transplant diabetes mellitus (PTDM) shows a relationship with risk factors including obesity and tacrolimus‐based immunosuppression, which decreases pancreatic insulin secretion. Several of the sodium–glucose‐linked transporter 2 inhibitors (SGLT2is) and glucagon‐like peptide 1 receptor agonists (GLP1‐RAs) dramatically improve outcomes of individuals with type 2 diabetes with and without chronic kidney disease, which is, as heart failure and atherosclerotic cardiovascular disease, differentially affected by both drug classes (presumably). Here, we discuss SGLT2is and GLP1‐RAs in context with other PTDM management strategies, including modification of immunosuppression, active lifestyle intervention, and early postoperative insulin administration. We also review recent studies with SGLT2is in PTDM, reporting their safety and antihyperglycemic efficacy, which is moderate to low, depending on kidney function. Finally, we reference retrospective case reports with GLP1‐RAs that have not brought forth major concerns, likely indicating that GLP1‐RAs are ideal for PTDM patients suffering from obesity. Although our article encompasses PTDM after solid organ transplantation in general, data from kidney transplant recipients constitute the largest proportion. The PTDM research community still requires data that treating and preventing PTDM will improve clinical conditions beyond hyperglycemia. We therefore suggest that it is time to collaborate, in testing novel antidiabetics among patients of all transplant disciplines.

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Section: Management Of Ptdm: Novel Antidiabeticsmentioning

confidence: 99%

Section: Management Of Ptdm: Novel Antidiabeticsmentioning

confidence: 99%

Section: Management Of Ptdm: Novel Antidiabeticsmentioning

confidence: 99%

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

et al. 2020

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2021

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Dulaglutide, a weekly injectable glucagon-like peptide-1 receptor agonist, has demonstrated effectiveness when combined with basal insulin. We examined whether the efficacy of dulaglutide is comparable to that of prandial insulin in kidney transplant (KT) recipients with type 2 diabetes mellitus (T2DM) undergoing multiple daily insulin injection (MDI) therapy. Thirty-seven patients, who switched from MDI therapy to basal insulin and dulaglutide, were retrospectively analyzed. Changes in glycosylated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels, body weight, and basal insulin dose were evaluated over 6 months. Dulaglutide was comparable to three injections of prandial insulin in terms of glycemic control (HbA1c 7.1% vs. 7.0%; 95% confidence interval [CI], -0.53 to 0.28; P=0.53). The basal insulin and dulaglutide combination resulted in a reduction in FPG levels by 9.7 mg/dL (95% CI, 2.09 to 41.54; P=0.03), in body weight by 4.9 kg (95% CI, 2.87 to 6.98; P<0.001), and in basal insulin dose by 9.52 IU (95% CI, 5.80 to 3.23; P<0.001). Once-weekly dulaglutide may be an effective alternative for thrice-daily prandial insulin in KT recipients with T2DM currently receiving MDI therapy.

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“…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].…”

Section: Clinical Experience With Glp‐1ra For Ptdm and Pre‐existent Diabetes In Sot Recipientsmentioning

confidence: 99%

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

et al. 2021

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Summary Post‐transplant diabetes mellitus (PTDM) is a common complication of solid organ transplantation and a major cause of increased morbidity and mortality. Additionally, solid organ transplant patients may have pre‐existent type 2 diabetes mellitus (T2DM). While insulin is the treatment of choice for hyperglycemia in the first weeks after transplantation, there is no preferred first line agent for long‐term management of PTDM or pre‐existent T2DM. Glucagon‐like peptide‐1 receptor agonists (GLP‐1RA) and sodium–glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control, lower body weight, and blood pressure, are recommended after lifestyle and metformin as initial therapy for diabetic patients with cardiovascular or kidney comorbidities regarding their cardiorenal benefits. Furthermore, the mechanisms of action of GLP‐1RA may counteract some of the driving forces for PTDM, as calcineurin‐induced β cell toxicity as per preclinical data, and improve obesity. However, their use in the treatment of PTDM is currently limited by a paucity of data. Retrospective observational and small exploratory studies suggest that GLP‐1RA effectively improve glycemic control and induce weight loss in patients with PTDM without interacting with commonly used immunosuppressive agents, although randomized‐controlled clinical trials are required to confirm their safety and efficacy. In this narrative review, we evaluate the risk factors and pathogenesis of PTDM and compare the potential roles of GLP‐1RA and SGLT2 inhibitors in PTDM prevention and management as well as in pre‐existent T2DM, and providing a roadmap for evidence generation on newer antidiabetic drugs for solid organ transplantation.

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

Cited by 37 publications

References 42 publications

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

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

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

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

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