The Effect of Metformin on Fat Distribution and the Metabolic Syndrome in Women With Polycystic Ovary Syndrome–A Randomised, Double-Blind, Placebo-Controlled Trial
Abstract
OBJECTIVE: To establish whether metformin has a significant action in reducing visceral fat and improving other metabolic parameters in women with polycystic ovary syndrome (PCOS). DESIGN: Randomised, double-blind, placebo-controlled trial. SETTING: Reproductive medicine clinic. POPULATION: Forty women with anovulatory PCOS. METHODS: Participants were randomised into receiving metformin 500 mg three times a day or placebo for 3 months. MAIN OUTCOME MEASURES: Fat distribution was measured by computed tomography scan. Secondary outcome measures included serum indices of the metabolic syndrome and evidence of ovulation. RESULTS: We found no significant differences in any of the measures of fat distribution between the placebo and metformin groups. The metformin group had significantly lower total cholesterol (P= 0.02), low-density lipoprotein cholesterol (P= 0.02) and cholesterol:high-density lipoprotein cholesterol ratio (P= 0.05), but there was no statistically significant treatment effect on androgens, insulin, insulin resistance, triglycerides, ovulation or pregnancy. CONCLUSIONS: Metformin has no clinically significant effect in reducing visceral fat mass, although it does have a beneficial effect on lipids. This trial lends support to the growing evidence that metformin is not a weight loss drug. Metformin might therefore be used as an adjunct to lifestyle modification in women with PCOS, but not as a substitute for it.
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Metformin has not been approved as a weight loss drug in part because its effects are highly variable and in women with PCOS despite weight loss visceral fat may not be reduced.
“However, metformin has not been approved as a weight loss drug in part because its effects are highly variable and in women with PCOS despite weight loss visceral fat may not be reduced (21).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [21]
Cites
Matthews, D. R., Hosker, J. P., Rudenski, A. S., Naylor, B. A., Treacher, D. F., & Turner, R. C. (1985) · Diabetologia · doi:10.1007/bf00280883 · Cited by 31,502 · see citing works
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
(2002) · New England Journal of Medicine · doi:10.1056/nejmoa012512 · Cited by 19,011 · see citing works
(2004) · Fertility and Sterility · doi:10.1016/j.fertnstert.2003.10.004 · Cited by 9,050 · see citing works
The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group (2004) · Human Reproduction · doi:10.1093/humrep/deh098 · Cited by 6,138 · see citing works
Use and Abuse of HOMA Modeling
Wallace, T. M., Levy, J. C., & Matthews, D. R. (2004) · Diabetes Care · doi:10.2337/diacare.27.6.1487 · Cited by 5,114 · see citing works
Orchard, T. J., Temprosa, M., Goldberg, R., Haffner, S., Ratner, R., Marcovina, S., Fowler, S., & for the Diabetes Prevention Program Research Group (2005) · Annals of Internal Medicine · doi:10.7326/0003-4819-142-8-200504190-00009 · Cited by 948 · see citing works
Treatment of obesity: need to focus on high risk abdominally obese patients
Despres, J., Lemieux, I., & Prud'homme, D. (2001) · British medical journal · doi:10.1136/bmj.322.7288.716 · Cited by 934 · see citing works
The metabolically obese, normal-weight individual revisited.
Ruderman, N., Chisholm, D., Pi-Sunyer, X., & Schneider, S. (1998) · Diabetes · doi:10.2337/diabetes.47.5.699 · Cited by 893 · see citing works
Metformin in polycystic ovary syndrome: systematic review and meta-analysis
Lord, J. M., Flight, I. H. K., & Norman, R. J. (2003) · BMJ · doi:10.1136/bmj.327.7421.951 · Cited by 786 · see citing works
Self-citationNestler, J. E., Jakubowicz, D. J., Evans, W. S., & Pasquali, R. (1998) · New England Journal of Medicine · doi:10.1056/nejm199806253382603 · Cited by 781 · see citing works
Legro, R. S., Finegood, D. T., & Dunaif, A. E. (1998) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.83.8.5054 · Cited by 748 · see citing works
Clark, A. M., Ledger, W., Galletly, C., Tomlinson, L., Blaney, F., Wang, X., & Norman, R. J. (1995) · Human Reproduction · doi:10.1093/oxfordjournals.humrep.a135772 · Cited by 642 · see citing works
Pasquali, R., Gambineri, A., Biscotti, D., Vicennati, V., Gagliardi, L., Colitta, D., Fiorini, S., Cognigni, G. E., Filicori, M., & Morselli-Labate, A. M. (2000) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.85.8.6738 · Cited by 635 · see citing works
Holte, J., Bergh, T., Berne, C., Wide, L., & Lithell, H. (1995) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.80.9.7673399 · Cited by 435 · see citing works
Adiposity, Fat Distribution, and Cardiovascular Risk
Peiris, A. N., Sothmann, M. S., Hoffmann, R. G., Hennes, M. I., Wilson, C. R., Gustafson, A. B., & Kissebah, A. H. (1989) · Annals of Internal Medicine · doi:10.7326/0003-4819-110-11-867 · Cited by 423 · see citing works
Surgical removal of visceral fat reverses hepatic insulin resistance.
Barzilai, N., She, L., Liu, B. Q., Vuguin, P. M., Cohen, P., Wang, J., & Rossetti, L. (1999) · Diabetes · doi:10.2337/diabetes.48.1.94 · Cited by 373 · see citing works
Tang, T. H., Norman, R. J., Balen, A. H., & Lord, J. M. (2003) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053 · Cited by 369 · see citing works
Self-citationFleming, R., Hopkinson, Z. E., Wallace, A. M., Greer, I. A., & Sattar, N. A. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.2.8261 · Cited by 366 · see citing works
Tang, T., Glanville, J., Hayden, C. J., White, D., Barth, J. H., & Balen, A. H. (2006) · Human Reproduction · doi:10.1093/humrep/dei311 · Cited by 335 · see citing works
The role of lifestyle modification in polycystic ovary syndrome
Norman, R. J., Davies, M. J., Lord, J., & Moran, L. J. (2002) · Trends in Endocrinology & Metabolism · doi:10.1016/s1043-2760(02)00612-4 · Cited by 326 · see citing works
Self-citationAdipose tissue volume determinations in women by computed tomography: technical considerations.
Kvist, H., Sjöström, L., & Tylén, U. (1986) · PubMed · Cited by 325 · see citing works
Pathophysiology and Pathogenesis of Visceral Fat Obesity
Matsuzawa, Y., Shimomura, I., Nakamura, T., Keno, Y., Kotani, K., & Tokunaga, K. (1995) · Obesity Research · doi:10.1002/j.1550-8528.1995.tb00462.x · Cited by 300 · see citing works
Kirchengast, S. (2001) · Human Reproduction · doi:10.1093/humrep/16.6.1255 · Cited by 291 · see citing works
Holte, J., Bergh, T., Berne, C., Berglund, L., & Lithell, H. (1994) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.78.5.8175959 · Cited by 290 · see citing works
Huber-Buchholz, M.-M. (1999) · Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.84.4.1470 · Cited by 269 · see citing works
Comparison of insulin sensitivity tests across a range of glucose tolerance from normal to diabetes
Hermans, M. P., Lévy, J., Morris, R. J., & Turner, R. C. (1999) · Diabetologia · doi:10.1007/s001250051215 · Cited by 260 · see citing works
Yamashita, S., Nakamura, T., Shimomura, L., Nishida, M., Yoshida, S., Kotani, K., Kameda-Takemuara, K., Tokunaga, K., & Matsuzawa, Y. (1996) · Diabetes Care · doi:10.2337/diacare.19.3.287 · Cited by 208 · see citing works
Després, J. (1994) · Baillière s Clinical Endocrinology and Metabolism · doi:10.1016/s0950-351x(05)80289-7 · Cited by 203 · see citing works
Yıldırım, B., Sabir, N., & Kaleli̇, B. (2003) · Fertility and Sterility · doi:10.1016/s0015-0282(03)00265-6 · Cited by 195 · see citing works
Ng, E. H. Y. (2001) · Human Reproduction · doi:10.1093/humrep/16.8.1625 · Cited by 183 · see citing works
Arner, P. (1998) · The Lancet · doi:10.1016/s0140-6736(05)79052-8 · Cited by 179 · see citing works
Holte, J., Bergh, T., Gennarelli, G., & WIDE, L. E. (1994) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1994.tb02578.x · Cited by 178 · see citing works
Anthropometric Variables and Metabolism in Polycystic Ovarian Disease
Rebuffé-Scrive, M., Cullberg, G., Lundberg, P. A., Lindstedt, G., & Björntorp, P. A. (1989) · Hormone and Metabolic Research · doi:10.1055/s-2007-1009245 · Cited by 142 · see citing works
New concepts in human sperm-zona pellucida interaction
Clark, G. F., Patankar, M. S., Hinsch, K., & Oehninger, S. (1995) · Human Reproduction · doi:10.1093/humrep/10.suppl_1.31 · Cited by 112 · see citing works
Body Fat Distribution in Women With Polycystic Ovary Syndrome
Douchi, T. (1995) · Obstetrics and Gynecology · doi:10.1016/0029-7844(95)00250-u · Cited by 81 · see citing works
Polycystic ovary syndrome and fat distribution: The central issue?
Lord, J. M., & Wilkin, T. J. (2002) · Human Fertility · doi:10.1080/1464727022000198952 · Cited by 55 · see citing works
Self-citationInfluences of weight, body fat patterning and nutrition on the management of PCOS
Lefebvre, P., Bringer, J., Renard, É., Boulet, F., Clouet, S., & Jaffiol, C. (1997) · Human Reproduction · doi:10.1093/humrep/12.suppl_1.72 · Cited by 53 · see citing works
Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome.
Dhindsa, G., Bhatia, R., Dhindsa, M., & Bhatia, V. (2004) · PubMed · Cited by 46 · see citing works
Increasing incidence of type 2 diabetes in the third millennium: is abdominal fat the central issue?
Samaras, K., & Campbell, L. V. (2000) · Diabetes Care · doi:10.2337/diacare.23.4.441 · Cited by 36 · see citing works
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Tang, T., Lord, J. M., Norman, R. J., Yasmin, E., & Balen, A. H. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053.pub5 · Cited by 698 · see citing works
Self-citationMorley, L. C., Tang, T., Yasmin, E., Norman, R. J., & Balen, A. H. (2017) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd003053.pub6 · Cited by 296 · see citing works
Elkind-Hirsch, K., Marrioneaux, O., Bhushan, M., Vernor, D., & Bhushan, R. (2008) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-0115 · Cited by 276 · see citing works
Mohammed, I., Hollenberg, M. D., Ding, H., & Triggle, C. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.718942 · Cited by 278 · see citing works
Wei, W., Zhao, H., Wang, A., Sui, M., Liang, K., Deng, H., Ma, Y., Zhang, Y., Zhang, H., & Guan, Y. (2012) · European Journal of Endocrinology · doi:10.1530/eje-11-0616 · Cited by 155 · see citing works
Elkind-Hirsch, K. E., Chappell, N., Seidemann, E., Storment, J., & Bellanger, D. (2021) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgab408 · Cited by 96 · see citing works
Melin, J., Forslund, M., Alesi, S., Piltonen, T., Romualdi, D., Spritzer, P. M., Tay, C. T., Pena, A., Witchel, S. F., Mousa, A., et al. (2023) · European Journal of Endocrinology · doi:10.1093/ejendo/lvad098 · Cited by 72 · see citing works
Patel, R., & Shah, G. (2017) · Current Medical Research and Opinion · doi:10.1080/03007995.2017.1279597 · Cited by 47 · see citing works
Penaforte, F. R. O., Japur, C. C., Diez-Garcia, R. W., & Chiarello, P. G. (2011) · Journal of Human Nutrition and Dietetics · doi:10.1111/j.1365-277x.2010.01130.x · Cited by 35 · see citing works
Bordewijk, E. M., Wang, R., van Wely, M., Costello, M. F., Norman, R. J., Teede, H., Gurrin, L. C., Mol, B. W., & Li, W. (2020) · Human Reproduction Update · doi:10.1093/humupd/dmaa031 · Cited by 18 · see citing works
- Authors
- Lord, J., Thomas, R., Fox, B., Acharya, U., & Wilkin, T.
- Affiliations
- Royal Cornwall Hospital Trust (GB)
- Royal Devon & Exeter NHS Foundation Trust (GB)
- Derriford Hospital (GB)
- Corresponding author
- Lord, J
- ORCID
- Lord, J
- Venue
- BJOG: An International Journal of Obstetrics & Gynaecology
- Publisher
- Wiley
- Published
- 2006-06-22
- Volume
- 113
- Issue
- 7
- Pages
- 817-824
- ISSN
- 0306-5456 (ISSN-L)
- 1470-0328
- 1471-0528
- OpenAlex
- W2076863250
- Cited by
- 113
- References
- 39
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 1 · 2023: 4 · 2022: 2 · 2021: 10 · 2020: 7 · 2019: 3 · 2017: 8 · 2016: 2 · 2015: 5 · 2014: 4 · 2013: 9 · 2012: 5
- FWCI
- 10.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- BJOG An International Journal of Obstetrics & Gynaecology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Kidney Cyst Diseases
- Keywords
- metformin, polycystic ovary syndrome, metabolic syndrome, visceral fat, body fat distribution, lipid profile, cholesterol, insulin resistance, ovulation, anovulation, weight loss, lifestyle modification
- MeSH terms
- Adult, Anovulation, Cholesterol, Double-Blind Method, Female, Humans, Hypoglycemic Agents, Metformin, Polycystic Ovary Syndrome, Observer Variation, Subcutaneous Fat, Intra-Abdominal Fat
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