Metabolic effects of metformin in non-insulin-dependent diabetes mellitus
Open accessAbstract
BACKGROUND: The metabolic effects and mechanism of action of metformin are still poorly understood, despite the fact that it has been used to treat patients with non-insulin-dependent diabetes mellitus (NIDDM) for more than 30 years. METHODS: In 10 obese patients with NIDDM, we used a combination of isotope dilution, indirect calorimetry, bioimpedance, and tissue-balance techniques to assess the effects of metformin on systemic lactate, glucose, and free-fatty-acid turnover; lactate oxidation and the conversion of lactate to glucose; skeletal-muscle glucose and lactate metabolism; body composition; and energy expenditure before and after four months of treatment. RESULTS: Metformin treatment decreased the mean (+/- SD) glycosylated hemoglobin value from 13.2 +/- 2.2 percent to 10.5 +/- 1.6 percent (P < 0.001) and reduced fasting plasma glucose concentrations from 220 +/- 41 to 155 +/- 28 mg per deciliter (12.2 +/- 0.7 to 8.6 +/- 0.5 mmol per liter) (P < 0.001). Although resting energy expenditure did not change, the patients lost 2.7 +/- 1.3 kg of weight (P < 0.001), 88 percent of which was adipose tissue. The mean (+/- SE) rate of plasma glucose turnover (hepatic glucose output and systemic glucose disposal) decreased from 2.8 +/- 0.2 to 2.0 +/- 0.2 mg per kilogram of body weight per minute (15.3 +/- 0.9 to 10.8 +/- 0.9 mumol per kilogram per minute) (P < 0.001), as a result of a decrease in hepatic glucose output; systemic glucose clearance did not change. The rate of conversion of lactate to glucose (gluconeogenesis) decreased by 37 percent (P < 0.001), whereas lactate oxidation increased by 25 percent (P < 0.001). There were no changes in the plasma lactate concentration, plasma lactate turnover, muscle lactate release, plasma free-fatty-acid turnover, or uptake of glucose by muscle. CONCLUSIONS: Metformin acts primarily by decreasing hepatic glucose output, largely by inhibiting gluconeogenesis. It also seems to induce weight loss, preferentially involving adipose tissue.
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Metformin-induced weight loss is almost exclusively confined to reductions in adipose mass with little change in lean tissue.
“This is because metformin-induced weight loss is almost exclusively confined to reductions in adipose mass (2,16,18) with little change in lean tissue.”
From Long-Term Safety, Tolerability, and Weight Loss Associated With Metformin in the Diabetes Prevention Program Outcomes Study (2012) · cites this paper as [18]
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Metformin prevents liver tumorigenesis induced by high-fat diet in C57Bl/6 mice
Tajima, K., Nakamura, A., Shirakawa, J., Togashi, Y., Orime, K., Sato, K., Inoue, H., Kaji, M., Sakamoto, E., Ito, Y., et al. (2013) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00133.2013 · Cited by 59 · see citing works
Use of metformin in the treatment of polycystic ovary syndrome
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Cholestatic jaundice associated with the use of metformin
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The Influence of Metformin on IGF-1 Levels in Humans: A Systematic Review and Meta-Analysis
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Effects of rosiglitazone and metformin on pancreatic beta cell gene expression
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Adenylyl Cyclase Type 5 Deficiency Protects Against Diet-Induced Obesity and Insulin Resistance
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Recent progress in the pharmacotherapy for obesity
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- Authors
- Stumvoll, M., Nurjhan, N., Perriello, G., Dailey, G., & Gerich, J. E.
- Affiliations
- University of Rochester Medicine (US)
- Scripps Clinic (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1995-08-31
- Volume
- 333
- Issue
- 9
- Pages
- 550-554
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2315982688
- Cited by
- 1,148
- References
- 33
- Citations by year
- 2026: 14 · 2025: 19 · 2024: 20 · 2023: 33 · 2022: 23 · 2021: 39 · 2020: 34 · 2019: 42 · 2018: 36 · 2017: 56 · 2016: 43 · 2015: 46 · 2014: 65 · 2013: 46 · 2012: 41
- FWCI
- 8.81
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (192/1-2)
- National Institutes of Health
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-20411)
- National Center for Research Resources (5MO1 RR-00044, M01RR000044, 5MO1-RR 000954)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- metformin, type 2 diabetes, hepatic glucose production, gluconeogenesis inhibition, lactate oxidation, glucose turnover, free fatty acid turnover, skeletal muscle glucose metabolism, weight loss, adipose tissue, energy expenditure, mechanism of action, HbA1c, fasting blood glucose, obesity, body composition, isotope dilution, indirect calorimetry
- MeSH terms
- Blood Glucose, Body Composition, Diabetes Mellitus, Diabetes Mellitus, Type 2, Energy Metabolism, Female, Glucose, Glycated Hemoglobin, Humans, Lactates, Male, Metformin, Middle Aged, Obesity, Muscle, Skeletal, Lactic Acid
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