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

Abstract

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.

• Authors: Lale A Ertuglu, Esteban Porrini, Mads Hornum, Atalay Demiray, Baris Afsar, Alberto Ortiz, Adrian Covic, Peter Rossing, Mehmet Kanbay
• Journal: Transplant international : official journal of the European Society for Organ Transplantation (Transpl Int) Vol. 34 Issue 8 Pg. 1341-1359 (Aug 2021) ISSN: 1432-2277 [Electronic] Switzerland
• PMID: 33880815 (Publication Type: Journal Article, Review)
• Copyright: © 2021 Steunstichting ESOT. Published by John Wiley & Sons Ltd.

Chemical References

• Glucagon-Like Peptide-1 Receptor
• Hypoglycemic Agents
• Sodium
• Glucose

Topics

• Diabetes Mellitus, Type 2 (complications, drug therapy)
• Glucagon-Like Peptide-1 Receptor
• Glucose
• Humans
• Hypoglycemic Agents (therapeutic use)
• Organ Transplantation
• Retrospective Studies
• Sodium