Effects of metformin on weight loss: potential mechanisms

Malin, Steven K.; Kashyap, Sangeeta R.

doi:10.1097/med.0000000000000095

Cited by 223Pharmacology and Obesity TreatmentRegulation of Appetite and ObesityBariatric Surgery and Outcomes

Effects of metformin on weight loss: potential mechanisms

Malin, Steven K., Kashyap, Sangeeta R.·2014·Current Opinion in Endocrinology, Diabetes & Obesity

DOI 10.1097/med.0000000000000095

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Abstract

PURPOSE OF REVIEW: Despite the known glucose-lowering effects of metformin, more recent clinical interest lies in its potential as a weight loss drug. Herein, we discuss the potential mechanisms by which metformin decreases appetite and opposes unfavorable fat storage in peripheral tissues. RECENT FINDINGS: Many individuals struggle to maintain clinically relevant weight loss from lifestyle and bariatric surgery interventions. Long-term follow-up from the Diabetes Prevention Program demonstrates that metformin produces durable weight loss, and decreased food intake by metformin is the primary weight loss mechanism. Although the effect of metformin on appetite is likely to be multifactorial, changes in hypothalamic physiology, including leptin and insulin sensitivity, have been documented. In addition, novel work in obesity highlights the gastrointestinal physiology and circadian rhythm changes by metformin as not only affecting food intake, but also the regulation of fat oxidation and storage in liver, skeletal muscle, and adipose tissue. SUMMARY: Metformin induces modest weight loss in overweight and obese individuals at risk for diabetes. A more detailed understanding of how metformin induces weight loss will likely lead to optimal co-prescription of lifestyle modification with pharmacology for the treatment of obesity independent of diabetes.

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Metformin prevents weight gain by influencing appetite regulatory pathways in the brain.
“prevent weight gain by influencing appetite regulatory pathways in the brain (8).”
From Metformin and Combined Oral Contraceptive Pills in the Management of Polycystic Ovary Syndrome: A Systematic Review and Meta-analysis (2024) · cites this paper as [8]
Recent study findings indicate that GDF-15 plays an independent role in body weight change in people taking metformin.
“Aside from the mechanisms summarized in two reviews (77, 78), recent study findings indicate that GDF-15 plays an independent role in body weight change in people taking metformin.”
From GDF-15 as a Weight Watcher for Diabetic and Non-Diabetic People Treated With Metformin (2020) · cites this paper as [77]
Metformin might reduce weight through appetite regulatory pathways in the brain, leading to decreased food uptake.
“Studies have suggested that metformin might reduce weight through appetite regulatory pathways in the brain, leading to decreased food uptake.50”
From The impact of metformin with or without lifestyle modification versus placebo on polycystic ovary syndrome: a systematic review and meta-analysis of randomized controlled trials (2023) · cites this paper as [50]

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Authors: Malin, S. K., & Kashyap, S. R.
Affiliations: Cleveland Clinic (US)
Corresponding author: Kashyap, Sangeeta R.
ORCID: Malin, Steven K.
Kashyap, Sangeeta R.
Venue: Current Opinion in Endocrinology, Diabetes & Obesity
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2014-10
Volume: 21
Issue: 5
Pages: 323-329
ISSN: 1752-296X (ISSN-L)
DOI: 10.1097/med.0000000000000095
OpenAlex: W2118790125
Cited by: 223
References: 43
Citations by year: 2026: 4 · 2025: 10 · 2024: 16 · 2023: 18 · 2022: 16 · 2021: 33 · 2020: 27 · 2019: 27 · 2018: 34 · 2017: 15 · 2016: 12 · 2015: 10 · 2012: 1
FWCI: 1.58
Type: journal article
Language: en
Open access: closed
Locations: Current Opinion in Endocrinology Diabetes and Obesity (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK089547)
National Center for Research Resources (K12RR023264)
Topics: Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
Keywords: metformin, weight loss, obesity, appetite, dietary intake, leptin, insulin sensitivity, fat oxidation, fat deposition, circadian rhythm, digestive physiology, diabetes prevention, lifestyle modification
MeSH terms: Appetite Depressants, Diabetes Mellitus, Type 2, Eating, Humans, Hypoglycemic Agents, Hypothalamus, Insulin Resistance, Metformin, Obesity, Signal Transduction, Weight Loss, Treatment Outcome, Leptin, Risk Reduction Behavior

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Effects of metformin on weight loss: potential mechanisms

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