Effects of GLP ‐1 receptor agonists on cognitive function in patients with type 2 diabetes: A systematic review and meta‐analysis based on randomized controlled trials

Abstract Aims Patients with type 2 diabetes mellitus (T2DM) have a significantly increased risk of cognitive impairment, and the protective effects of traditional hypoglycaemic drugs on cognitive function remain unclear. This study systematically evaluated the neuroprotective effects of GLP‐1 receptor agonists (GLP‐1RAs) based on randomized controlled trial (RCT) evidence, aiming to provide key evidence‐based insights for optimizing diabetes management strategies. Materials and Methods A comprehensive literature search was conducted across PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and ClinicalTrials.gov databases to identify studies investigating the impact of GLP‐1RAs on cognitive function in T2DM patients, with the search timeframe extending up to July 2025. The analysis focused on RCTs comparing the effects of GLP‐1RAs versus placebo (or conventional therapy) on neurocognitive function in T2DM patients. Results Based on the inclusion criteria, 18 RCTs involving 11 114 participants were included in the primary meta‐analysis. Pooled results demonstrated that, compared to the placebo group, GLP‐1RA treatment significantly increased Mini‐Mental State Examination (MMSE) scores by a weighted mean difference (WMD) of 1.33 (95% CI: 0.67–1.99; I 2 = 82%) and Montreal Cognitive Assessment (MoCA) scores by a WMD of 1.70 (95% CI: 0.83–2.56; I 2 = 96%). The effect size on MMSE was significantly greater with long‐term GLP‐1RA use (≥24 weeks) compared to short‐term use (<24 weeks) (mean difference = 3.74; t = 6.52, df = 269, p < 0.0001; Cohen's d = 0.79). Sensitivity analyses yielded results closely aligned with the primary analysis, indicating robust stability. Jadad scale assessment confirmed that all included studies achieved a score ≥3. Conclusions Current evidence indicates that GLP‐1 RA‐based therapy may improve cognitive function in patients with type 2 diabetes mellitus compared with placebo. Furthermore, long‐term administration or early initiation of GLP‐1 RA treatment may offer greater cognitive benefits.