Date of Award

Spring 2026

Document Type

Scholarly Project

Degree Name

Master of Physician Assistant Studies (MPAS)

Department

Physician Assistant Studies

First Advisor

Julie Solberg

Keywords

Metformin, Diabetes Mellitus

Abstract

Dementia is a leading cause of disability in older adults, and type 2 diabetes mellitus (T2DM) is a major modifiable risk factor for cognitive decline.  Metformin, the first-line therapy for T2DM, has demonstrated anti-inflammatory, vascular and neuroprotective properties that may influence cognition beyond glycemic control.  This literature review evaluated whether metformin improves cognitive outcomes in adults compared with placebo or alternative antidiabetic medications.  A search of PubMed and Embase identified eight studies meeting inclusion criteria including observational cohorts, comparative effectiveness analyses, Mendelian randomization and one randomized crossover trial.  Most studies reported that metformin use was associated with reduces dementia risk and slower cognitive decline compared with untreated duabete3sm independent if HbA1c. Comparative studies suggested potential cognitive advantages of SGLT2 inhibitors and thiazolidinediones, while sulfonylureas were linked to higher risk.  Genetic analyses supported non-glycemic mechanisms, and limited randomized data demonstrated short term improvement in executive function.  Overall, evidence suggests metformin may contribute to cognitive preservation, though definitive conclusions require large randomized trials with standardized cognitive outcomes.

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