Some newer hypoglycemic agents showed outcome-specific neuropsychiatric benefits, especially high-dose dapagliflozin for delirium and depression.
Evidence
A frequentist with Bayesian robustness checks included 62 randomized trials and 200,068 participants without baseline cognitive psychiatric disorders.
Caveat
Benefits were agent- and endpoint-specific, with no significant benefit for dementia or coma across agents.
Simplified
OBJECTIVES: Emerging evidence suggests that glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose co-transporter 2 (SGLT2) inhibitors may exert neuroprotective effects. However, the comparative efficacy of individual agents remains unclear. This (NMA) aimed to evaluate the differential impacts of these therapies on the incidence of mental status changes, specifically delirium, depression, dementia and coma.
DESIGN: A frequentist NMA was conducted using data from randomised controlled trials (RCTs) investigating GLP-1 receptor agonists SGLT2 inhibitors. The robustness of the findings was verified through a Bayesian NMA framework.
SETTING: This study adopted a confirmatory framework focusing on pre-defined neuropsychiatric adverse outcomes in alignment with Cochrane recommendations.
PARTICIPANTS: Included trials enrolled individuals without baseline cognitive or psychiatric disorders.
MAIN OUTCOME MEASURES: The primary endpoint was the incidence of delirium, depression, dementia or coma during treatment. Secondary endpoints included changes in cognitive performance and drop-out rates.
RESULTS: A total of 62 RCTs comprising 200,068 participants were included. Among all treatments, only high-dose dapagliflozin (10 mg/day) significantly reduced the occurrence of delirium and depression, particularly in patients with type 2 diabetes. Dulaglutide and liraglutide were the only agents associated with cognitive improvement. No significant benefits were observed for dementia or coma across all agents.
CONCLUSIONS: This analysis highlights agent-specific neuroprotective profiles: SGLT2 inhibitors, especially high-dose dapagliflozin, may mitigate the onset of delirium and depression, while GLP-1 receptor agonists, notably dulaglutide and liraglutide, may enhance cognitive function. These findings warrant consideration in selecting antihyperglycemic therapies for individuals at elevated neuropsychiatric risk.
TRIAL REGISTRATION: PROSPERO CRD42024601021.The study protocol was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical Center (TSGHIRB E202516007).
Key numbers
0.21
Decrease in Delirium Incidence
for delirium incidence with dapagliflozin (10 mg/day) vs. placebo.
0.43
Decrease in Depression Risk
for depression incidence with dapagliflozin (10 mg/day) vs. placebo.
1.46
Cognitive Improvement with Dulaglutide
for cognitive function with dulaglutide vs. controls.
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