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Anti-obesity medications and cognitive disorder risk: a discrepancy between RCTs and real-world evidence

Chengwen Li1, Chu Lin1,2,3, Zonglin Li1

  • 1Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.

Frontiers in Pharmacology
|July 15, 2026
PubMed
Abstract

Insights

Anti-obesity medications (AOMs) showed no cognitive benefits in short-term trials. However, real-world data suggests glucagon-like peptide-1 receptor agonists (GLP-1RAs) may protect against cognitive disorders.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Public Health

Background:

  • Overweight and obesity are associated with an increased risk of cognitive disorders.
  • Anti-obesity medications (AOMs) aim to reduce weight, potentially impacting cognitive health.
  • The relationship between AOM use and cognitive outcomes requires further investigation.

Purpose of the Study:

  • To investigate the association between anti-obesity medication (AOM) use and the risk of cognitive disorder in individuals with overweight and obesity.
  • To evaluate the impact of AOMs on cognitive decline and dementia risk.

Main Methods:

  • Systematic literature search of PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov.
  • Inclusion of randomized controlled trials (RCTs) and observational studies of AOMs.
  • Meta-analysis using random-effect models to calculate relative risks and odds ratios.

Main Results:

  • RCTs (n=35,924) found no significant association between AOM use and lower risk of cognitive disorder or dementia versus placebo.
  • Weight loss from AOMs did not correlate with reduced cognitive disorder risk in RCTs.
  • Retrospective cohort studies (n=2,303,492) indicated GLP-1RA users had lower risks of cognitive disorder and Alzheimer's disease compared to non-users.

Conclusions:

  • Short-term RCTs do not support cognitive benefits from AOMs.
  • Real-world evidence suggests GLP-1RAs may offer protection against cognitive disorders.
  • Long-term prospective trials with specific cognitive endpoints are needed to clarify these findings.
Keywords:
alzheimer’s diseaseanti-obesity medicationscognitive disorderdementiameta-analysis

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