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The concentration-dependent protective effects by new generation hypoglycemic agents on delirium, depression,

Ping-Tao Tseng1,2,3,4, Bing-Yan Zeng2,5, Chih-Wei Hsu6

  • 1Institute of Precision Medicine, National Sun Yat-sen University, Kaohsiung 804, Taiwan.

Journal of the Royal Society of Medicine
|December 8, 2025
PubMed
Abstract

Insights

Glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors show neuroprotective potential. High-dose dapagliflozin reduced delirium and depression, while dulaglutide and liraglutide improved cognition in this network meta-analysis.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Endocrinology

Background:

  • Emerging evidence suggests neuroprotective effects of GLP-1 receptor agonists and SGLT2 inhibitors.
  • Comparative efficacy of these agents for neuropsychiatric outcomes is unclear.
  • This network meta-analysis (NMA) addresses this knowledge gap.

Purpose of the Study:

  • To evaluate the differential impacts of GLP-1 receptor agonists and SGLT2 inhibitors on mental status changes.
  • To compare the efficacy of these therapies in preventing delirium, depression, dementia, and coma.
  • To identify agent-specific neuroprotective profiles.

Main Methods:

  • A frequentist network meta-analysis (NMA) was conducted using data from randomized controlled trials (RCTs).
  • Bayesian NMA framework was used to verify robustness of findings.
  • Included trials enrolled individuals without baseline cognitive or psychiatric disorders.

Main Results:

  • 62 RCTs with 200,068 participants were analyzed.
  • High-dose dapagliflozin (10 mg/day) significantly reduced delirium and depression, especially in type 2 diabetes patients.
  • Dulaglutide and liraglutide were associated with cognitive improvement; no benefits for dementia or coma were observed.

Conclusions:

  • SGLT2 inhibitors, particularly high-dose dapagliflozin, may mitigate delirium and depression onset.
  • GLP-1 receptor agonists, specifically dulaglutide and liraglutide, may enhance cognitive function.
  • Findings support agent-specific considerations for antihyperglycemic therapies in individuals at elevated neuropsychiatric risk.
Keywords:
GLP-1 receptor agonistNetwork meta-analysisSGLT2 inhibitordeliriumdepressionmental status

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