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- British Journal of Clinical Pharmacology: Metformin for Olanzapine-Induced Weight Gain: A Systematic Review and Meta-Analysis
- British Journal of Clinical Pharmacology: Metformin for Olanzapine-Induced Weight Gain: A Systematic Review and Meta-Analysis
- Aging: Metformin in Obesity, Cancer and Aging: Addressing Controversies
- Aging: Metformin in Obesity, Cancer and Aging: Addressing Controversies
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Non-Diabetic Uses of Metformin
Although the U.S. Food and Drug Administration oversees the safety and effectiveness of drugs prescribed by American doctors, it does not regulate the practice of medicine. So, many medications are used “off-label,” meaning your doctor may prescribe a drug for purposes that have not yet been approved by the FDA. About 1/5 of the prescriptions for common medications are written for an off-label use, according to a 2012 review in “Mayo Clinic Proceedings.” Metformin (Glucophage), a drug licensed to treat type 2 diabetes, has a number of off-label uses 1.
If you are experiencing serious medical symptoms, seek emergency treatment immediately.
How Metformin Works
Metformin is unlike other medications used to treat type 2 diabetes. Although all of its actions are not completely understood, metformin’s main mode of action is to decrease glucose production in your liver. In addition, metformin increases your cells’ sensitivity to the insulin released from your pancreas, which increases your body’s ability to metabolize glucose. Together, these actions reduce your blood glucose level without driving it too low. These same properties make the drug potentially useful in a number of situations.
- Metformin is unlike other medications used to treat type 2 diabetes.
- Although all of its actions are not completely understood, metformin’s main mode of action is to decrease glucose production in your liver.
Drug-Induced Weight Gain
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Atypical antipsychotic medications, such as olanzapine (Zyprexa), are prescribed for managing schizophrenia, bipolar disorder and other conditions. But in many people, these medications cause significant weight gain, which is believed to stem from drug-induced appetite stimulation and insulin resistance.
A March 2011 analysis in the “British Journal of Clinical Pharmacology” showed people who gain weight as a result of taking olanzapine may lose some of that weight by also taking metformin 3. This has important implications for people whose psychiatric conditions cannot be controlled without atypical antipsychotics. Metformin may not be appropriate for everyone who takes olanzapine or similar medications.
- Atypical antipsychotic medications, such as olanzapine (Zyprexa), are prescribed for managing schizophrenia, bipolar disorder and other conditions.
Obesity
Obesity is by nature an insulin-resistant state. As your body mass and body fat percentage increase, so does your resistance to insulin. According to a May 2012 review in “Aging,” metformin exerts a moderate weight-reducing effect in obese people. This effect is smaller than lifestyle changes, such as a reduced-calorie diet and exercise. Nonetheless, when prescribed by a doctor, metformin may be a useful addition to anti-obesity treatment. Similarly, metformin may help address other insulin-resistant states, such as fatty liver disease and metabolic syndrome, which is sometimes called prediabetes.
- Obesity is by nature an insulin-resistant state.
- Nonetheless, when prescribed by a doctor, metformin may be a useful addition to anti-obesity treatment.
Polycystic Ovary Syndrome
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Up to 15 percent of reproductive-aged women suffer from polycystic ovary syndrome, which is characterized by menstrual irregularities, low fertility, obesity and high blood levels of male hormones. Scientists have discovered that many women with PCOS are also insulin resistant, which stimulates their ovaries to produce male hormones.
By increasing insulin sensitivity and decreasing the ovarian production of male hormones, metformin stabilizes hormone levels, improves menstrual regularity and possibly improves ovulation and fertility in women with PCOS. Furthermore, when women with PCOS do conceive, metformin appears to improve their chances of carrying their pregnancy to term. While metformin is commonly prescribed for women with PCOS, its use must be determined on a case-by-case basis.
- Up to 15 percent of reproductive-aged women suffer from polycystic ovary syndrome, which is characterized by menstrual irregularities, low fertility, obesity and high blood levels of male hormones.
- By increasing insulin sensitivity and decreasing the ovarian production of male hormones, metformin stabilizes hormone levels, improves menstrual regularity and possibly improves ovulation and fertility in women with PCOS.
Intriguing Possibilities
Given metformin’s actions in certain medical disorders, and because of what is known about its cellular and molecular activities, some researchers believe this medication may have anti-aging and anti-cancer effects 24. An emerging body of evidence suggests some forms of cancer and certain chronic diseases may be driven by insulin resistance. Metformin’s usefulness in these areas remains to be proven, and the FDA has not approved the drug for preventing cancer or reversing the effects of aging 4.
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References
- Mayo Clinic Proceedings: Ten Common Questions (and Their Answers) About Off-Label Drug Use
- Clinical Science: Cellular and Molecular Mechanisms of Metformin: An Overview
- British Journal of Clinical Pharmacology: Metformin for Olanzapine-Induced Weight Gain: A Systematic Review and Meta-Analysis
- Aging: Metformin in Obesity, Cancer and Aging: Addressing Controversies
- Goodman NF, Cobin RH, Futterweit W, Glueck JS, Legro RS, Carmina E. AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS, AMERICAN COLLEGE OF ENDOCRINOLOGY, AND ANDROGEN EXCESS AND PCOS SOCIETY DISEASE STATE CLINICAL REVIEW: GUIDE TO THE BEST PRACTICES IN THE EVALUATION AND TREATMENT OF POLYCYSTIC OVARY SYNDROME - PART 2. Endocr Pract. 2015;21(12):1415-1426. doi:10.4158/EP15748.DSCPT2
- Vitek W, Alur S, Hoeger KM. Off-label drug use in the treatment of polycystic ovary syndrome. Fertil Steril. 2015;103(3):605-611. doi:10.1016/j.fertnstert.2015.01.019
- Salber GJ, Wang YB, Lynch JT, et al. Metformin Use in Practice: Compliance With Guidelines for Patients With Diabetes and Preserved Renal Function. Clin Diabetes. 2017;35(3):154-161. doi:10.2337/cd15-0045
- Ibáñez L, López-Bermejo A, Díaz M, Marcos MV, de Zegher F. Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence. J Clin Endocrinol Metab. 2011;96(8):E1262-E1267. doi:10.1210/jc.2011-0555
- Lashen H. Role of metformin in the management of polycystic ovary syndrome. Ther Adv Endocrinol Metab. 2010;1(3):117-128. doi:10.1177/2042018810380215
- Priya G, Kalra S. Metformin in the management of diabetes during pregnancy and lactation. Drugs Context. 2018;7:212523. doi:10.7573/dic.212523
- Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014;19(7):658–664.
- Corcoran C, Jacobs TF. Metformin. [Updated 2020 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK518983/
- Aroda VR, Edelstein SL, Goldberg RB, et al. Long-term Metformin Use and Vitamin B12 Deficiency in the Diabetes Prevention Program Outcomes Study. J Clin Endocrinol Metab. 2016;101(4):1754-1761. doi:10.1210/jc.2015-3754
- Wang YW, He SJ, Feng X, et al. Metformin: a review of its potential indications. Drug Des Devel Ther. 2017;11:2421-2429. doi:10.2147/DDDT.S141675
- Choudhury H, Pandey M, Hua CK, et al. An update on natural compounds in the remedy of diabetes mellitus: A systematic review. J Tradit Complement Med. 2017;8(3):361–376. Published 2017 Nov 29. doi:10.1016/j.jtcme.2017.08.012
- Chhetri DR. Myo-Inositol and Its Derivatives: Their Emerging Role in the Treatment of Human Diseases. Front Pharmacol. 2019;10:1172. Published 2019 Oct 11. doi:10.3389/fphar.2019.01172
- Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574-579. doi:10.1056/NEJM199602293340906
- Costantino D, Minozzi G, Minozzi E, Guaraldi C. Metabolic and hormonal effects of myo-inositol in women with polycystic ovary syndrome: a double-blind trial. Eur Rev Med Pharmacol Sci. 2009;13(2):105-110.
- Galazis N, Galazi M, Atiomo W. D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol. 2011;27(4):256-262. doi:10.3109/09513590.2010.538099
- Genazzani AD, Prati A, Santagni S, et al. Differential insulin response to myo-inositol administration in obese polycystic ovary syndrome patients. Gynecol Endocrinol. 2012;28(12):969-973. doi:10.3109/09513590.2012.685205
- Gerli S, Papaleo E, Ferrari A, Di Renzo GC. Randomized, double blind placebo-controlled trial: effects of myo-inositol on ovarian function and metabolic factors in women with PCOS. Eur Rev Med Pharmacol Sci. 2007;11(5):347-354.
- Le Donne M, Alibrandi A, Giarrusso R, Lo Monaco I, Muraca U. [Diet, metformin and inositol in overweight and obese women with polycystic ovary syndrome: effects on body composition]. Minerva Ginecol. 2012;64(1):23-29.
- Oner G, Muderris II. Clinical, endocrine and metabolic effects of metformin vs N-acetyl-cysteine in women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol. 2011;159(1):127-131. doi:10.1016/j.ejogrb.2011.07.005
- Papaleo E, Unfer V, Baillargeon J-P, et al. Myo-inositol in patients with polycystic ovary syndrome: a novel method for ovulation induction. Gynecol Endocrinol. 2007;23(12):700-703. doi:10.1080/09513590701672405
- Raffone E, Rizzo P, Benedetto V. Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol. 2010;26(4):275-280. doi:10.3109/09513590903366996
- Venturella R, Mocciaro R, De Trana E, D’Alessandro P, Morelli M, Zullo F. [Assessment of the modification of the clinical, endocrinal and metabolical profile of patients with PCOS syndrome treated with myo-inositol]. Minerva Ginecol. 2012;64(3):239-243.
- Zhuo Z, Wang A, Yu H. Effect of metformin intervention during pregnancy on the gestational diabetes mellitus in women with polycystic ovary syndrome: a systematic review and meta-analysis. J Diabetes Res. 2014;2014:381231. doi:10.1155/2014/381231
Writer Bio
Stephen Christensen started writing health-related articles in 1976 and his work has appeared in diverse publications including professional journals, “Birds and Blooms” magazine, poetry anthologies and children's books. He received his medical degree from the University of Utah School of Medicine and completed a three-year residency in family medicine at McKay-Dee Hospital Center in Ogden, Utah.