The effect of GLP-1 receptor agonists on osteoarthritis risk in individuals with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized controlled trials.

objectiveCurrent research has not yet drawn a definitive conclusion on the impact of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on the risk of osteoarthritis (OA) in patients with type 2 diabetes mellitus (T2DM). To supplement the evidence base in this field, the present study sought to systematically investigate the association between GLP-1RA administration and the risk of OA in adult T2DM patients through a meta-analysis of relevant randomized controlled trials (RCTs).

methodsAn exhaustive literature search was conducted across five major databases-PubMed, Embase, Web of Science, ClinicalTrials.gov, and the Cochrane Library-covering the period from each database's inception up to May 6, 2025. The main objective of this literature search was to identify RCTs that enrolled adult patients with T2DM receiving GLP-1RAs and reported OA incidence. The Cochrane Risk of Bias 2.0 tool was employed to evaluate the risk of bias for all included studies, while the GRADE system was applied to assess the overall certainty of the evidence. Additionally, the node-splitting method was utilized to perform inconsistency testing between direct and indirect evidence. The occurrence of OA events was defined as the primary outcome of the study. A series of analyses were performed to evaluate the impact of each intervention on OA risk, including traditional meta-analysis, frequentist network meta-analysis (NMA), and sensitivity analysis. Summary estimates of effect size were presented as relative risk (RR) along with 95% confidence intervals (CI).

resultsThe present study ultimately included 74 RCTs with a combined sample size of 105,415 individuals. Conventional pairwise meta-analysis revealed no statistically significant difference in OA risk between GLP-1RAs and placebo, insulin, or other oral antidiabetic drugs (OADs). Stratified subgroup analyses based on GLP-1RA formulation, treatment duration, and control group type also found no statistically significant differences in OA risk across all subgroups. Furthermore, NMA results indicated no notable variations in OA risk between GLP-1RAs and control interventions, and no such differences were observed among the different GLP-1RA formulations either. Sensitivity analyses verified the stability and reliability of the study outcomes.

conclusionsAmong adult patients with T2DM, there was no significant difference in OA risk between GLP-1RA treatment and placebo, insulin, or OADs; this absence of statistical significance was also observed across different GLP-1RA formulations, varying treatment durations, and distinct control groups. PROSPERO REGISTRATION NUMBER: CRD420251034203.