Glucagon‐like peptide‐1 receptor agonists and sodium‐glucose cotransporter‐2 inhibitors for the treatment of diabetes mellitus in liver transplant recipients

Author:

Zheng Katina1ORCID,Azhie Amirhossein2,You Xiaoting1,Naghibzadeh Maryam2,Tan Eunice2,Naimimohasses Sara2,Sridhar Vikas S.13ORCID,Gupta Sarang1,Chen Shiyi2,Dash Satya245,Tsien Cynthia1267,Selzner Nazia1267,Lilly Leslie1267,Jaeckel Elmar1267,Woo Minna145,Singh Sunita13,Cherney David13,Bhat Mamatha1267ORCID

Affiliation:

1. Department of Medicine University of Toronto Toronto Ontario Canada

2. Multi Organ Transplant Program University Health Network Toronto Ontario Canada

3. Division of Nephrology University of Toronto Toronto Ontario Canada

4. Division of Endocrinology and Metabolism University Health Network Toronto Ontario Canada

5. Division of Endocrinology and Metabolism University of Toronto Toronto Ontario Canada

6. Division of Gastroenterology and Hepatology University Health Network Toronto Ontario Canada

7. Division of Gastroenterology and Hepatology University of Toronto Toronto Ontario Canada

Abstract

AbstractAimTo investigate the efficacy and safety of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) and sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in liver transplant (LT) recipients with diabetes.MethodsA single‐centre, retrospective analysis of prospectively collected data from an LT recipient database (1990–2023) was conducted. We included adults with pre‐existing diabetes and post‐transplant diabetes, newly started on GLP‐1RAs and/or SGLT2 inhibitors after LT. Metabolic and biochemical parameters and outcomes were collected for up to 12 months after starting medications and were compared to those in patients receiving dipeptidyl peptidase‐4 (DPP‐4) inhibitors. Statistical analysis included descriptive statistics and linear mixed models.ResultsWe included participants on GLP‐1RAs (n = 46), SGLT2 inhibitors (n = 87), combination therapy (n = 12), and a DPP‐4 inhibitor comparator (n = 217). Both GLP‐1RAs and combination therapy decreased mean glycated haemoglobin (HbA1c) levels, and combination therapy remained significant when adjusted for DPP‐4 inhibitor treatment (−3.5%, 95% CI [−6.1, −0.95]; p = 0.0089) at 12 months. All three groups had significant decreases in mean weight and body mass index, but these remained significant in the GLP‐1RA (−5.2 kg, 95% CI [−8.7, −1.7], p = 0.0039 and 1.99 kg/m2, 95% CI [−3.4, −0.6], p = 0.0048) and combination therapy groups (−5.4 kg, 95% CI [−10.5, −0.36], p = 0.04 and −3.4 kg/m2, 95% CI [−5.5, −1.3], p = 0.0015) when adjusted for DPP‐4 inhibitor treatment at 12 months. Alanine aminotransferase levels decreased with GLP‐1RA and combination therapy. There were two (1.4%) cases of graft rejection.ConclusionWe found that GLP‐1RAs, SGLT2 inhibitors, and their combination, led to significant weight loss in LT recipients with diabetes. Combination therapy, in particular, lowered HbA1c and alanine aminotransferase levels compared to DPP‐4 inhibitors. Further studies are needed to assess long‐term safety and efficacy.

Publisher

Wiley

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