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.