Introduction and Objective: GLP-1 receptor agonists (GLP-1 RAs) are recognized for glycemic and metabolic benefits in type 2 diabetes and obesity. Emerging evidence suggests neuroprotective effects via GLP-1 receptor expression in key brain regions. This study evaluated whether GLP-1 RA therapy is associated with measurable changes in cognitive function via MMSE.Methods: This retrospective cohort study used de-identified EMRs from the Gonzaba Medical Group. Adults aged ≥18 years with ≥2 MMSE assessments and complete confounder data were included (n = 529). The intervention group received GLP-1 RAs, while the comparator group met identical criteria but excluded GLP-1 RA use. Linear regression analyzed relationships between GLP-1 RA use, MMSE scores, and confounders.Results: The population was predominantly female (57%), diabetic (53%), and Hispanic (96%), with a mean age of 74 years and BMI of 29.7 kg/m². At baseline, the GLP-1 RA group exhibited significant differences from the control group, including higher MMSE, longer assessment intervals, more diabetics, lower age, and higher BMI, resulting in baseline confounding.GLP-1 RA-treated subjects showed a BMI reduction of 0.91 kg/m² (p<0.01) versus controls. Cognitive decline occurred in all groups. In the GLP-1 RA group, each 1 kg/m² BMI decrease was associated with a 0.067-point MMSE increase, though not statistically significant (p=0.69).Conclusion: Baseline confounding highlights the need for better control in future studies. Improvement in MMSE scores among GLP-1 RA-treated subjects suggests that weight loss may be critical to achieving proposed neuroprotective effects. Findings warrant further exploration in randomized controlled studies.
C.A. Dehn: None. L. Ballester: Research Support; NeuroBo Pharmaceuticals, Inc, Biogen, Boston Pharmaceuticals, Vigil Neuroscience, BioXcel Therapeutics, Braeburn Pharmaceuticals, Ceruvia Lifesciences, Karuna Therapeutics, Ensysce Biosciences, Fulcrum Therapeutics, Xgene Pharmaceuticals, Urica Therapeutics, Crystalys Biotherapeutics, TLC Biosciences, PainReform, LTD Therapeutics Inc, Kenvue, Graviton Bioscience, Gate Bioscience, Antibe Therapeutics, Park Therapeutics, ProMIS Neurosciences. M. Paulos: None. V.G. Gonzaba: None. E. Tireman: None. T.A. Karnes: None. W. Martin: Employee; Alkermes, Inc. Advisory Panel; Axial Therapeutics. S.L. Schwartz: None.
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