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

Diabetes Obes Metab. 2024 Oct;26(10):4261-4272. doi: 10.1111/dom.15769. Epub 2024 Jul 26.

Abstract

Aim: To 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.

Methods: A 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.

Results: We 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.

Conclusion: We 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.

Keywords: DPP‐4 inhibitors; GLP‐1 receptor agonists; SGLT2 inhibitors; diabetes mellitus; liver transplantation.

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2* / blood
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Dipeptidyl-Peptidase IV Inhibitors* / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Glucagon-Like Peptide-1 Receptor Agonists
  • Glucagon-Like Peptide-1 Receptor* / agonists
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents* / therapeutic use
  • Liver Transplantation*
  • Male
  • Middle Aged
  • Retrospective Studies
  • Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use
  • Treatment Outcome

Substances

  • Sodium-Glucose Transporter 2 Inhibitors
  • Glucagon-Like Peptide-1 Receptor
  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Glycated Hemoglobin
  • hemoglobin A1c protein, human
  • Blood Glucose
  • Glucagon-Like Peptide-1 Receptor Agonists