Comparison of the GLP-1 Receptor Agonists with other anti-obesity/anti-diabetic medicines: a systematic review

Abstract

Obesity and type 2 diabetes are increasing and place demands on health systems. Comparative evidence across medicines that influence body weight and glycaemic control is needed. This systematic review compared GLP-1 receptor agonists (GLP-1 RA) with SGLT2 inhibitors, DPP-4 inhibitors, and orlistat in adults with type 2 diabetes or obesity without diabetes. Primary variables were body weight and HbA1c, and safety outcomes were recorded. PRISMA 2020 methods were applied. MEDLINE, Embase, CENTRAL, ClinicalTrials.gov, and WHO ICTRP were searched (2016–2025, English). One reviewer screened, selected, and extracted data. Twenty studies were included. Evidence was synthesised narratively using thematic analysis; no meta-analysis was conducted. GLP-1 RA (semaglutide and liraglutide) and the dual incretin tirzepatide produced the largest reductions in weight and HbA1c. SGLT2 inhibitors produced modest improvements in outcomes. DPP-4 inhibitors were weight-neutral with smaller HbA1c reductions. Orlistat produced small to moderate weight loss with limited glycaemic benefit. Safety signals were observed: gastrointestinal symptoms were frequent with GLP-1 agents and tirzepatide; genitourinary infections were common with SGLT2 inhibitors; orlistat was limited by gastrointestinal intolerance; DPP-4 inhibitors showed a benign profile. Findings support prioritising GLP-1 RA or tirzepatide when substantial weight loss and HbA1c reduction are required, with individualisation by comorbidity and tolerance. Limitations include single-reviewer methods, heterogeneity, English-only searches, and absence of meta-analysis. Future work should test head-to-head trials and assess durability beyond 72 weeks.

Keywords: GLP-1 receptor agonists; tirzepatide; SGLT2 inhibitors; DPP-4 inhibitors; obesity; type 2 diabetes; systematic review.