Metformin is an antidiabetic agent used as a first line treatment option for Type II diabetes. Its mechanism of action remains unknown and its applications may prove to be useful for other conditions including:
Studies show that patients with prediabetes who take metformin are less likely to have blood glucose levels in the diabetic range after three years. As such, metformin may be used to prevent the development of diabetes in people at risk.1
Metformin has been found to be useful in the treatment of polycystic ovary syndrome (PCOS). It lowers serum androgens, normalizes menstrual cycles and ovulation, and may improve pregnancy rates.2
While metformin has not received FDA approval for treating obesity, researchers have found it to be effective in reducing weight in insulin sensitive and insulin resistant overweight and obese patients.3, 4, 5 It has also been studied in preventing antipsychotic-induced weight gain.6
All-cause mortality reduction have been described in observational studies and long-term follow-up in patients receiving metformin.7, 8 Additionally, several epidemiologic studies have shown that metformin use is associated with reduced cancer incidence and cancer mortality.9-14 Moreover, there is evidence from studies performed both in vitro and in vivo of metformin’s role in attenuating tumorigenesis.15-20 Emerging data also suggests that metformin may preserve cognitive function.21-25 Topical metformin cream has been found to be an effective treatment of melasma.26 More research is needed for the FDA to approve metformin for its use in these other conditions.
Side Effect Profile
Metformin is generally considered a relatively safe drug and the risk of hypoglycemia is minimal. The most significant (and very rare) potential side effect of metformin use is lactic acidosis. The most common side effects of oral metformin formulations are related to gut complications and include upset stomach, nausea, vomiting, diarrhea, lightheadedness, or a metallic taste in the mouth.27 One in three patients taking oral metformin will experience these effects, which may lead some to discontinue therapy. In these instances, metformin cream may be a viable alternative. The formulation allows the drug to be absorbed through the skin while bypassing the gastrointestinal system and thus avoiding many of the unpleasant side effects.28
Metformin is indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus. It is also used off-label as a treatment for prediabetes, gestational diabetes and PCOS.
Metformin was first used in Europe in the 1950’s but was not approved by the FDA until 1994. Today, metformin is available commercially as oral tablets in select doses. Both regular-release and extended-release formulations exist.
Since metformin is already commercially available orally, metformin cream is reserved for patients who cannot tolerate oral metformin or who cannot swallow large tablets as determined by a health care provider. The preparation is commonly compounded at Galleria Medical Pharmacy in the following strengths, though other strengths and formulations may be available upon request:
Metformin 50 mg/gm Cream
Metformin 100 mg/gm Cream
Note: Patients require about a 10% dose of the cream formulation as compared to the oral formulation (e.g., a person taking 500 mg of metformin tablets would require 50 mg from metformin cream).
Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.
- Lily M, Godwin M. Treating prediabetes with metformin: systematic review and meta-analysis [published correction appears in Can Fam Physician. 2010 Jan;56(1):18. Lilly, Muriel [corrected to Lily, Muriel]]. Can Fam Physician. 2009;55(4):363-369.
- Kosasa TS. Making a Case for Metformin. OB/GYN 2003;48:69-80.
- Seifarth C., et al. Effectiveness of metformin on weight loss in non-diabetic individuals with obesity. Exp Clin Endocrinol Diabetes. 2013 Jan;121(1):27-31.
- Malin, Steven K.a; Kashyap, Sangeeta R.bEffects of metformin on weight loss, Current Opinion in Endocrinology & Diabetes and Obesity: October 2014 – Volume 21 – Issue 5 – p 323-329.
- Armen Yerevanian, Alexander A. Soukas. Metformin: Mechanisms in Human Obesity and Weight Loss. Curr Obes Rep. 2019 Jun; 8(2): 156-164.
- de Silva, V.A., Suraweera, C., Ratnatunga, S.S. et al.Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry 16, 341 (2016).
- Bannister CA, Holden SE, Jenkins-Jones S, Morgan CL, Halcox JP, Schernthaner G, Mukherjee J, Currie CJ. Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes Obes Metab. 2014;16:1165–1173.
- UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) 1998;352:854–865.
- Landman GW, Kleefstra N, van Hateren KJ, Groenier KH, Gans RO, Bilo HJ. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care. 2010;33:322–326.
- Lee MS, Hsu CC, Wahlqvist ML, Tsai HN, Chang YH, Huang YC. Type 2 diabetes increases and metformin reduces total, colorectal, liver and pancreatic cancer incidences in Taiwanese: a representative population prospective cohort study of 800,000 individuals. BMC Cancer. 2011;11:20.
- Libby G, Donnelly LA, Donnan PT, Alessi DR, Morris AD, Evans JM. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes. Diabetes Care.
- Monami M, Colombi C, Balzi D, Dicembrini I, Giannini S, Melani C, Vitale V, Romano D, Barchielli A, Marchionni N, et al. Metformin and cancer occurrence in insulin-treated type 2 diabetic patients. Diabetes Care. 2011;34:129–131.
- Stevens RJ, Ali R, Bankhead CR, Bethel MA, Cairns BJ, Camisasca RP, Crowe FL, Farmer AJ, Harrison S, Hirst JA, et al. Cancer outcomes and all-cause mortality in adults allocated to metformin: systematic review and collaborative meta-analysis of randomised clinical trials. 2012;55:2593–2603.
- Gandini S, Puntoni M, Heckman-Stoddard BM, Dunn BK, Ford L, DeCensi A, Szabo E. Metformin and cancer risk and mortality: a systematic review and meta-analysis taking into account biases and confounders. Cancer Prev Res (Phila) 2014;7:867–885.
- Anisimov VN, Bartke A. The key role of growth hormone-insulin-IGF-1 signaling in aging and cancer. Crit Rev Oncol Hematol. 2013;87:201–223.
- Karnevi E, Said K, Andersson R, Rosendahl AH. Metformin-mediated growth inhibition involves suppression of the IGF-I receptor signaling pathway in human pancreatic cancer cells. BMC Cancer. 2013;13:235.
- Liu B, Fan Z, Edgerton SM, Yang X, Lind SE, Thor AD. Potent anti-proliferative effects of metformin on trastuzumab-resistant breast cancer cells via inhibition of erbB2/IGF-1 receptor interactions. Cell Cycle. 2011;10:2959–2966.
- Quinn BJ, Dallos M, Kitagawa H, Kunnumakkara AB, Memmott RM, Hollander MC, Gills JJ, Dennis PA. Inhibition of lung tumorigenesis by metformin is associated with decreased plasma IGF-I and diminished receptor tyrosine kinase signaling. Cancer Prev Res (Phila) 2013;6:801–810.
- Salani B, Maffioli S, Hamoudane M, Parodi A, Ravera S, Passalacqua M, Alama A, Nhiri M, Cordera R, Maggi D. Caveolin-1 is essential for metformin inhibitory effect on IGF1 action in non-small-cell lung cancer cells. FASEB J. 2012;26:788–798.
- Tosca L, Ramé C, Chabrolle C, Tesseraud S, Dupont J. Metformin decreases IGF1-induced cell proliferation and protein synthesis through AMP-activated protein kinase in cultured bovine granulosa cells. 2010;139:409–418.
- Ng TP, Feng L, Yap KB, Lee TS, Tan CH, Winblad B. Long-term metformin usage and cognitive function among older adults with diabetes. J Alzheimers Dis. 2014;41:61–68.
- Cheng C, Lin CH, Tsai YW, Tsai CJ, Chou PH, Lan TH. Type 2 diabetes and antidiabetic medications in relation to dementia diagnosis. J Gerontol A Biol Sci Med Sci. 2014;69:1299–1305.
- Moore EM, Mander AG, Ames D, Kotowicz MA, Carne RP, Brodaty H, Woodward M, Boundy K, Ellis KA, Bush AI, et al. AIBL Investigators. Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care. 2013;36:2981–2987.
- Alagiakrishnan K, Sankaralingam S, Ghosh M, Mereu L, Senior P. Antidiabetic drugs and their potential role in treating mild cognitive impairment and Alzheimer’s disease. Discov Med. 2013;16:277–286.
- Guo M, Mi J, Jiang QM, Xu JM, Tang YY, Tian G, Wang B. Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus. Clin Exp Pharmacol Physiol. 2014;41:650–656.
- Ali Mapar, M., Hemmati, A. A., & Namdari, G. (2019). Comparing the Efficacy of Topical Metformin and Placebo in the Treatment of Melasma: A Randomized, Double-blind, Clinical Trial. Journal of Pharmaceutical Research International, 30(4), 1-8.
- Nasri H, Rafieian-Kopaei M. Metformin: Current knowledge. J Res Med Sci. 2014;19(7):658-664.
- Polonini H, Cândido PJL, Andrade JL, Loures S, Raposo NR, Brandão MAF, Ferreira AO. Transdermal Delivery of Metformin Hydrochloride from a Semisolid Vehicle. Int J Pharm Compd. 2019 Jan-Feb;23(1):65-69.
Compounding Pharmacy Statement
This preparation is compounded with drug components whose suppliers are registered with the FDA. While Galleria Medical Pharmacy adheres to USP <795> guidelines and applicable state and federal regulations to meet the required quality standards, the statements made regarding this preparation have not been evaluated by the FDA for safety or clinical effectiveness. As such, this preparation is not intended to diagnose, treat, cure, or prevent any disease. For inquiries concerning this preparation, please contact (504) 267-9876.