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Background <p>Currently, the cognitive impact of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remains unclear in non-diabetic patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), despite their widespread use for type 2 diabetes. This meta-analysis summarized cognitive outcomes from randomized controlled trials (RCTs) of GLP-1 RAs in non-diabetic patients with AD or MCI.</p> Methods <p>PubMed, Cochrane Library, and Embase were searched for studies through October 27, 2024. Pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated using random-effects models. Sensitivity analyses addressed variations in cognitive assessment methodologies. Between-study heterogeneity was evaluated using the I² index.</p> Results <p>Four RCTs comprising 112 patients (61 placebo, 51 treatment) were included. For cognitive tests where higher scores indicate better outcomes, no significant difference was observed between GLP-1 RA and placebo groups (pooled SMD: -0.10, 95% CI: -0.53, 0.34; I² = 23.9%). Sensitivity analyses yielded consistent results. Analysis of the Alzheimer’s Disease Assessment Scale–Cognitive subscale from two studies, where lower scores indicate better outcomes, similarly showed no significant treatment effect (SMD: 0.07, 95% CI: -0.47, 0.62; I² = 0%).</p> Conclusion <p>There was no evidence that GLP-1 RAs improved cognitive outcomes compared to placebo in non-diabetic patients with AD or MCI. Further research is needed to clarify their neuroprotective potential and explore alternative therapeutic strategies for cognitive decline.</p>

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The effect of GLP-1 receptor agonists on cognition in nondiabetic patients with mild cognitive impairment or Alzheimer’s disease: a meta-analysis of randomized controlled trials

  • 期刊论文

  • 发表日期：

    2026年1月12日

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  • Ashley O’Mara,
  • Bhakti Pradip Mody,
  • Marco Mammi,
  • Thomas Simjian,
  • Kyrellos Ghattas,
  • Srilekha Kaliki,
  • Ngoc Phuong Mai Le,
  • Aaron Liew,
  • Mattia Migliore,
  • Rania A. Mekary

摘要

Background

Currently, the cognitive impact of Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) remains unclear in non-diabetic patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI), despite their widespread use for type 2 diabetes. This meta-analysis summarized cognitive outcomes from randomized controlled trials (RCTs) of GLP-1 RAs in non-diabetic patients with AD or MCI.

Methods

PubMed, Cochrane Library, and Embase were searched for studies through October 27, 2024. Pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated using random-effects models. Sensitivity analyses addressed variations in cognitive assessment methodologies. Between-study heterogeneity was evaluated using the I² index.

Results

Four RCTs comprising 112 patients (61 placebo, 51 treatment) were included. For cognitive tests where higher scores indicate better outcomes, no significant difference was observed between GLP-1 RA and placebo groups (pooled SMD: -0.10, 95% CI: -0.53, 0.34; I² = 23.9%). Sensitivity analyses yielded consistent results. Analysis of the Alzheimer’s Disease Assessment Scale–Cognitive subscale from two studies, where lower scores indicate better outcomes, similarly showed no significant treatment effect (SMD: 0.07, 95% CI: -0.47, 0.62; I² = 0%).

Conclusion

There was no evidence that GLP-1 RAs improved cognitive outcomes compared to placebo in non-diabetic patients with AD or MCI. Further research is needed to clarify their neuroprotective potential and explore alternative therapeutic strategies for cognitive decline.