Comparison of the effectiveness and safety of GLP-1 receptor agonists for type 2 diabetes mellitus patients with overweight/obesity: A systematic review and network meta-analysis

Diabetes Res Clin Pract. 2025 Apr:222:111999. doi: 10.1016/j.diabres.2025.111999. Epub 2025 Jan 17.

Abstract

Objective: To evaluate the effectiveness and safety of different Glucagon-like peptide-1 receptor agonists (GLP-1RAs) in treating type 2 diabetes mellitus (T2DM) with overweight/obesity using a systematic review and network meta-analysis.

Methods: We searched PubMed, Embase, Cochrane Library, and Web of Science up to December 20, 2024, for randomized controlled trials (RCTs) involving T2DM patients with overweight/obesity treated with GLP-1RAs, with the control group receiving either a placebo or another GLP-1RA. We conducted a network meta-analysis assessed evidence using CINeMA.

Results: A total of 4548 articles were retrieved, and 41 RCTs were included, comprising 15,126 patients and 13 different GLP-1RAs. Tirzepatide showed superior effects in lowering blood glucose (Compared with placebo, increased glycated hemoglobin: -1.64 (-1.94, -1.35), increased fasting blood glucose: -2.10 (-2.95, -1.25)) and weight loss (Compared with placebo, increased weight: -9.89 (-11.29, -8.49), rincreased BMI: -3.85 (-4.71, -2.99)). However, clinical efficacy of GLP-1RAs in lipid levels, blood pressure, and pancreatic function was not widely observed. Adverse reactions were significant with GLP-1RAs, but overall acceptable.

Conclusion: GLP-1RAs demonstrate efficacy and safety in T2DM patients with overweight/obesity, with certain advantages over other drugs. However, due to limitations in the number and quality of included studies, conclusions should be interpreted with caution.

Keywords: GLP-1 Receptor Agonists; Network Meta-Analysis; Overweight/Obesity; Systematic Review; Type 2 Diabetes Mellitus.

Publication types

  • Comparative Study
  • Network Meta-Analysis
  • Systematic Review

MeSH terms

  • Blood Glucose / drug effects
  • Diabetes Mellitus, Type 2* / complications
  • Diabetes Mellitus, Type 2* / drug therapy
  • Glucagon-Like Peptide-1 Receptor Agonists*
  • Glycated Hemoglobin
  • Humans
  • Hypoglycemic Agents* / adverse effects
  • Hypoglycemic Agents* / therapeutic use
  • Obesity* / complications
  • Obesity* / drug therapy
  • Overweight* / complications
  • Overweight* / drug therapy
  • Randomized Controlled Trials as Topic
  • Treatment Outcome

Substances

  • Blood Glucose
  • Glucagon-Like Peptide-1 Receptor Agonists
  • Glycated Hemoglobin
  • Hypoglycemic Agents