Utility of Pharmacological Agents for Diabetes Mellitus in the Prevention of Alzheimer's Disease: Comparison of Metformin, Glucagon-Like Peptide-1 (GLP-1) Agonists, Insulin, and Sulfonylureas.

BACKGROUND

Metformin is a drug primarily used for the treatment of diabetes mellitus (DM), but it also offers clinical benefits that extend beyond glycemic control. Existing literature provides an unclear conclusion as to whether metformin's benefits extend to preventing neurodegeneration, such as in Alzheimer's disease (AD).

METHODS

A retrospective database study was conducted to evaluate the likelihood of developing AD in DM patients taking metformin compared to those taking glucagon-like peptide (GLP-1) analogs, sulfonylureas, and short-acting insulin variants. An analysis was also run to assess whether metformin has a protective benefit for AD and mortality when used in those with DM compared to those without DM.

RESULTS

In analyses totaling greater than 2.5 million patients, those on metformin had lower A1C percentages and a decreased mortality risk when compared to sulfonylureas (HR = 0.519, (CI: (0.493,0.546)), and short-acting insulins (HR = 0.372, (CI: (0.364,0.380)). Metformin use for DM was associated with a statistically significant increased likelihood of AD diagnosis compared to GLP-1 use (HR = 2.228, CI: (1.036,4.794)) but an insignificant difference compared to both sulfonylureas and insulins. Those with DM were at a significantly higher risk of being diagnosed with Alzheimer's compared to those without DM (HR = 1.826, (CI: 1.579, 2.111)).

CONCLUSIONS

Metformin, previously thought to have significant benefits in preventing neurodegeneration, may not be the optimal pharmacologic agent of choice, particularly in patients with DM, if neurodegeneration is a primary concern in treatment decision-making based on other risk factors.