Comparative efficacy and safety of Glucagon‐like pepetide‐1 receptor agonists with metformin in Asian versus non‐Asian patients with type 2 diabetes: A systematic review and meta‐analysis

Aims In type 2 diabetes, glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) in combination with metformin show better efficacy than metformin alone. Nevertheless, the reactions of different ethnic groups, especially Asian and non‐Asian populations, are still controversial. To give clinical medication usage an evidence‐based foundation, this meta‐analysis examined GLP‐1RAs' safety and efficacy when combined with metformin in the treatment of type 2 diabetes mellitus. Materials and Methods Up to January 2025, systematic searches for randomised controlled trials were carried out in PubMed, Embase, the Cochrane Library, SinoMed and Wanfang comparing GLP‐1RA/metformin combination versus metformin alone in type 2 diabetes, with subgroup analyses for Asian versus non‐Asian cohorts. RevMan version 5.3 was used for analyses, and the Cochrane tools for risk of bias were used for quality assessment. Results This meta‐analysis comprised 11 papers in total (6 Asian trials: 750 people; 5 non‐Asian trials: 1096 people). After treatment of GLP‐1RAs combined with metformin, the Asian group showed greater improvement in glycosylated haemoglobin (HbA1c) (weighted mean differences [WMD], −1.09; 95% confidence intervals [CI], −1.48 to −0.71; subgroup heterogeneity: I 2 = 77.7%, p < 0.05) and weight (WMD, −4.16; 95% CI −6.11 to −2.22; subgroup heterogeneity: I 2 = 89.5%, p < 0.05) with a lower gastrointestinal (GI) events risk (relative risks, 0.76; 95% CI, 0.47 to 1.22; subgroup heterogeneity: I 2 = 93.7%, p < 0.00001). There were no racial variations in fasting glucose levels ( p = 0.78) or hypoglycaemia ( p = 0.16). Conclusions This meta‐analysis suggested potential ethnic variations in the treatment combining GLP‐1RAs with metformin, with Asian populations achieving superior HbA1c reduction and weight loss alongside better GI tolerance.