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CHARLA ALLEN, MD, KAYDEN BARBER, MD, BRIAN MALLORY, MD, AND ANNALEE TOTI, MD

Am Fam Physician. 2025;112(1):79-80

Author disclosure: No relevant financial relationships.

CLINICAL QUESTION

In patients with prediabetes, does metformin decrease the mortality rate compared with placebo?

EVIDENCE-BASED ANSWER

A large, multicenter, randomized controlled trial (RCT) with extended follow-up showed that metformin does not decrease the mortality rate in patients with prediabetes. (Strength of Recommendation [SOR]: A, review of prospective cohort studies, RCTs, systematic reviews, and meta-analyses.) In patients with prediabetes, metformin reduces progression to diabetes. (SOR: B, systematic review with disease-oriented outcomes.) Metformin does not reduce the rate of cardiovascular deaths compared with placebo. (SOR: B, single RCT.)

EVIDENCE SUMMARY

In a 2023 systematic review of 110 studies that included prospective cohort studies, RCTs, systematic reviews, and meta-analyses, lifestyle modification and medication use were compared with placebo in adults with prediabetes.1 Of the studies, three RCTs specifically focused on metformin (n = 3,972). Measured outcomes included incidence of progression to diabetes, cardiovascular events, and mortality after the studied interventions. Lifestyle modification consisted of caloric restriction, increased physical activity (150 min/week or more), self-monitoring, and motivational support. Trials included at least 2 years of follow-up.

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Help Desk Answers provides answers to questions submitted by practicing family physicians to the Family Physicians Inquiries Network (FPIN). Members of the network select questions based on their relevance to family medicine. Answers are drawn from an approved set of evidence-based resources and undergo peer review. The strength of recommendations and the level of evidence for individual studies are rated using criteria developed by the Evidence-Based Medicine Working Group (https://www.cebm.net).

The complete database of evidence-based questions and answers is copyrighted by FPIN. If interested in submitting questions or writing answers for this series, go to https://www.fpin.org or email: questions@fpin.org.

This series is coordinated by John E. Delzell Jr., MD, MSPH, associate medical editor.

A collection of FPIN’s Help Desk Answers published in AFP is available at https://www.aafp.org/afp/hda.

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