Metformin Protects Against Dementia, Mortality in Obesity

Metformin has a protective effect and may help reduce risk of all-cause mortality and dementia among patients with obesity, according to study findings published in Diabetes, Obesity and Metabolism.

To assess the real-world association between metformin use and long-term incidence of all-cause mortality and dementia among patients with obesity, investigators conducted a multicenter cohort study using electronic health records from the US Collaborative Network in June 2025. Patients aged at least 18 years who were prescribed metformin at least twice with a 6-month interval between prescriptions were divided into body mass index (BMI) categories of:

• 25.0 to 29.0 kg/m² (overweight; n=132,920);
• 30.0 to 34.9 kg/m² (obesity class I; n=142,723);
• 35.0 to 39.9 kg/m² (obesity class II; n=94,402); and,
• Over 40.0 kg/m² (morbid obesity; n=82,732).

Participants were then propensity-score matched 1:1 with individuals not prescribed metformin. After matching, all covariates were well-balanced between groups (including demographics, comorbidities, tobacco use, alcohol-related disorders, and use of medications related to obesity and dementia).

Compared with the control group, metformin users had significantly lower risks of both all-cause mortality and dementia across a 10-year follow-up period. All-cause mortality hazard ratios (HRs) for each BMI group were:

• 0.719 (95% CI, 0.701-0.737; overweight);
• 0.727 (95% CI, 0.708-0.746; obesity class I);
• 0.717 (95% CI, 0.694-0.741; obesity class II); and,
• 0.743 (95% CI, 0.717-0.771; morbid obesity).

Dementia HRs across each BMI group were:

• 0.875 (95% CI, 0.848-0.904; overweight);
• 0.917 (95% CI, 0.885-0.951; obesity class);
• 0.878 (95% CI, 0.834-0.924; obesity class II); and,
• 0.891 (95% CI, 0.834-0.953; morbid obesity).

In sensitivity analysis with data from the Asia-Pacific Collaborative Network, HRs for all-cause mortality were similar to the US Collaborative results for metformin users. However, the researchers observed neutral results for dementia risk across all BMI categories.

Stratifying the US Collaborative group by patients below 65 years of age and at least 65 years of age showed consistent results for all-cause mortality. However, among patients younger than 65 years of age, those with overweight or morbidly obese BMIs had neutral HRs for dementia, and those with obesity class I or class II BMI had favorable HRs for dementia. Among patients at least 65 years of age, only obesity class II had a neutral HR in dementia; all other groups had favorable HRs.

Study limitations include inherent coding issues in electronic data, and follow-up of 10 years precluded evaluation of longer-term effects of metformin.

“In this large, multi-center cohort study, metformin use was associated with reduced risks of dementia and all-cause mortality in obese patients,” the investigators concluded. “The protective effect was observed across all BMI groups, with variations noted by population. These findings support the potential of metformin in lowering dementia risk in patients with obesity.”

This article originally appeared on Endocrinology Advisor