Objective  To evaluate the efficacy and safety of glucagon-like peptide 1 receptor agonists (GLP-1RA) in type 2 diabetes mellitus (T2DM) patients with overweight or obese.

Methods  PubMed, Embase, Cochrane Library, Ovid, ClinicalTrial.gov, SinoMed, CNKI, WanFang Data and VIP databases were electronically searched to collect randomized controlled trials (RCTs) on the efficacy of GLP-1RA in the treatment of T2DM patients with overweight or obese from January 1, 2005 to November 1, 2023. Two researchers independently screened the literature, extracted data and evaluated the risk of bias of the included studies. R software was then used for meta-analysis. The level of evidence was assessed by using the GRADE system.

Results  A total of 71 RCTs were included, including 29 476 patients. The results of Meta-analysis showed that compared with other hypoglycemic drugs, GLP-1RA showed superior effects in improving HbA1c status (WMD=-0.55, 95%CI -0.65 to -0.45, P<0.001) and weight loss (WMD=-2.61, 95%CI -3.25 to -1.97, P<0.001), while the effect on fasting plasm glucose was time-dependent (within 16 weeks: WMD=0.25, 95%CI -0.17 to 0.66, P=0.250; 16 to 52 weeks: WMD=-0.06, 95%CI -0.32 to 0.20, P=0.650; over 52 to 104 weeks: WMD=-1.67, 95%CI -1.91 to -1.43, P<0.001). In terms of safety, the incidence of GLP-1RA’s adverse reactions was higher than other hypoglycemic drugs (RR=1.11, 95%CI 1.07 to 1.15, P<0.001); the incidence of hypoglycemia was lower with GLP-1RA than with insulin (RR=0.58, 95%CI 0.48 to 0.71, P<0.001) and similar to oral hypoglycemic drugs (RR=0.83, 95%CI 0.58 to 1.19, P=0.310). According to the GRADE assessment, only the certainty of the evidence for the results of the incidence of hypoglycemia was moderate, and the certainty of the evidence for the other results was low.

Conclusion  Current evidence shows that for T2DM patients with overweight or obese, GLP-1RA especially semaglutide, was more effective in lowering blood glucose, controlling body weight and reducing the occurrence of hypoglycemia than placebo, insulin and oral hypoglycemic drugs.

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