Efficacy and Safety of GLP-1 Receptor Agonists and SGLT-2 Inhibitors in the Treatment of Diabetes Mellitus and Obesity in Liver Transplant Recipients: A Systematic Review

Abstract

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) have significantly improved the management of diabetes mellitus (DM). In the general population, these drugs have additional benefits, such as weight loss, improvement of liver steatosis, and a cardiorenal protective effect. However, data regarding the effects of GLP-1RAs or SGLT-2Is in the treatment of posttransplant diabetes mellitus (PTDM), obesity, and their potential cardiorenal protective effects in liver transplant (LT) recipients remain limited. PTDM increases the risk of developing graft steatosis, experiencing major cardiovascular events (MACEs), and developing chronic kidney disease and reduces long-term survival in LT recipients. The aim of this systematic review was to evaluate the efficacy and safety of GLP-1RAs and SGLT-2Is in the treatment of PTDM in LT recipients. Methods: Twelve retrospective studies (five specifically conducted in LT recipients and seven in mixed solid organ transplant cohorts, including LT recipients) that collectively enrolled 402 LT recipients treated with GLP-1RAs and/or SGLT-2Is for PTDM were selected. Results: GLP-1Ras and SGLT-2Is reduced serum glycated hemoglobin levels, body weight, and insulin requirements in LT recipients. Some studies reported benefits in reducing graft steatosis, improving renal function, and in reducing the occurrence of MACEs. Common adverse events included gastrointestinal symptoms, which rarely required treatment discontinuation. Conclusions: GLP-1RAs and SGLT-2Is represent promising treatment options for PTDM in LT recipients, offering metabolic benefits with manageable side effects. However, further prospective studies are needed to establish the long-term safety and efficacy, as well as the favorable impact on patient survival, of these drugs in LT recipients.

Keywords: glucagon-like peptide-1 receptor agonists; graft steatosis; liver transplantation; obesity; posttransplant diabetes mellitus; sodium-glucose cotransporter-2 inhibitors.

Figure 1

PRISMA 2020 flow diagram for the proposed systematic review, which included searches of databases and registers only. Adapted from: Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ 2021;372:71. Atthota et al. [26]; Zheng et al. [27]; Yakubu et al. [28]; Richardson et al. [29]; Chow et al. [30].

Figure 2

(A) refers to the risk of bias assessment for the studies enrolling only liver transplant (LT) recipients [26,27,28,29,30]; (B) refers to the risk of bias assessment for the studies enrolling solid organ transplant [31,32,33,34,35,36,37].