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Metformin: Mechanisms in Human Obesity and Weight Loss

Current Obesity Reports volume 8, pages 156–164 (2019)Cite this article

Abstract

Purpose of Review

Metformin has multiple benefits for health beyond its anti-hyperglycemic properties. The purpose of this manuscript is to review the mechanisms that underlie metformin’s effects on obesity.

Recent Findings

Metformin is a first-line therapy for type 2 diabetes. Large cohort studies have shown weight loss benefits associated with metformin therapy. Metabolic consequences were traditionally thought to underlie this effect, including reduction in hepatic gluconeogenesis and reduction in insulin production. Emerging evidence suggests that metformin-associated weight loss is due to modulation of hypothalamic appetite regulatory centers, alteration in the gut microbiome, and reversal of consequences of aging. Metformin is also being explored in the management of obesity’s sequelae such as hepatic steatosis, obstructive sleep apnea, and osteoarthritis.

Summary

Multiple mechanisms underlie the weight loss–inducing and health-promoting effects of metformin. Further exploration of these pathways may be important in identifying new pharmacologic targets for obesity and other aging-associated metabolic diseases.

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Acknowledgments

We wish to acknowledge Scott Leighton for creating the figure for this review.

Funding

This work was supported by NIH R01AG058256, R01DK101522, and R01DK072041, the Weissman Family MGH Research Scholar Award, and a Glenn Award for Research in the Biological Mechanisms of Aging (to AS). AY is supported by the NIH-NIDDK funded MGH Endocrinology training grant T32DK007028.

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  1. Department of Medicine, Diabetes Unit, Endocrine Division, and Center for Genomic Medicine, Massachusetts General Hospital, 185 Cambridge Street, CPZN6224, Boston, MA, 02114, USA

    Armen Yerevanian & Alexander A. Soukas

  2. Department of Medicine, Harvard Medical School, Boston, MA, 02114, USA

    Armen Yerevanian & Alexander A. Soukas

  3. Broad Institute of Harvard and MIT, Cambridge, MA, 02142, USA

    Armen Yerevanian & Alexander A. Soukas

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  1. Armen Yerevanian
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Correspondence to Alexander A. Soukas.

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Yerevanian, A., Soukas, A.A. Metformin: Mechanisms in Human Obesity and Weight Loss. Curr Obes Rep 8, 156–164 (2019). https://doi.org/10.1007/s13679-019-00335-3

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  • DOI: https://doi.org/10.1007/s13679-019-00335-3

Keywords

  • Metformin
  • Obesity
  • Weight loss
  • Appetite regulation
  • Type 2 diabetes
  • Aging