Glucagon-Like Peptide 1 Analogues as Adjunctive Therapy for Patients With Type 1 Diabetes: An Updated Systematic Review and Meta-analysis

Abstract

Context: Concomitant obesity is common among patients with type 1 diabetes mellitus (T1DM), yet adjunctive therapy options are scarce.

Objective: We assess the efficacy and adverse outcomes of glucagon-like peptide 1 (GLP-1) analogues when used as adjunctive therapy for T1DM.

Method: PubMed, EMBASE, Cochrane Central, and Scopus databases were searched for randomized controlled trials up to December 2022. Efficacy outcomes were A1c level, body weight, and total daily insulin (TDI) after ≥12 weeks of GLP-1 therapy. We also assessed 12 different adverse outcomes. Subgroup analysis was done for newly diagnosed or C-peptide positive (C-pos) patients. We report the certainty of evidence based on the GRADE assessment tool.

Results: A total of 24 studies using 4 different GLP-1 analogues with a total of 3377 patients were included. Liraglutide had the most substantial evidence with effect sizes on A1c (-0.09%/mg), weight (-2.2 kg/mg), and TDI (-4.32 IU/mg). Liraglutide dose was the greatest predictor of greater average weight loss and TDI decrease but was associated with higher odds of nausea (OR 6.5; 95% CI, 5.0-8.4) and ketosis (OR 1.8; 95% CI, 1.1-2.8). Odds of severe (OR 0.67; 95% CI, 0.43-1.04) or symptomatic hypoglycemia (OR 0.89; 95% CI, 0.53-1.51) were not significantly elevated. Among C-pos patients, greater A1c decrease (-0.51% vs -0.28%) but similar weight loss and TDI were seen. Effect sizes for exenatide were similar, but studies had higher risk of bias and safety data were sparse.

Conclusion: Our meta-analysis supports therapeutic benefits of liraglutide for patients with T1DM mainly for weight loss and insulin dose reduction. Newly diagnosed or C-pos patients do not appear to experience greater weight loss benefits.

Keywords: glucagon-like peptide 1 analogues; meta-analysis; new-onset type 1 diabetes mellitus; type 1 diabetes mellitus; weight management.