Description

Overview of Metformin Cream

Dosage Strengths of Metformin Cream

10% 100 mL Pump

20% 100 mL Pump

General Information

Metformin is a drug that is commonly used to manage type 2 diabetes. However, recent studies have shown that metformin may also have potential therapeutic effects on skin conditions. Metformin cream has been shown to be effective in the treatment of a variety of dermatological conditions, including acne, seborrheic dermatitis, and psoriasis.

A study published in the Journal of Investigative Dermatology found that metformin cream significantly improved acne symptoms in patients with mild to moderate acne. Another study published in the Journal of the European Academy of Dermatology and Venereology found that metformin cream was effective in reducing seborrheic dermatitis symptoms. Although more research is needed, these studies suggest that metformin cream may be a promising treatment option for certain skin conditions.

Metformin, a medication used to treat diabetes, belongs to the class of oral biguanide drugs, which includes phenformin. Phenformin was removed from the US market in 1977 because it was associated with the occurrence of lactic acidosis, a serious medical condition. The risk for this adverse reaction is considerably lower with metformin, however. The actions of metformin differ from, yet complement, those of the sulfonylureas and other antidiabetic therapies. Compared to glyburide in type 2 diabetes, metformin was found to achieve similar glycemic control. although it lead to a higher incidence of digestive complaints. Metformin has been found useful in the treatment of polycystic ovary syndrome (PCOS); it lowers serum androgens and restores normal menstrual cycles and ovulation, and may improve pregnancy rates. Additionally, limited data indicate that it may delay puberty onset in females with precocious puberty and delay menarche onset in females with early-normal onset of puberty. The use of metformin versus intensive lifestyle modification in patients with impaired glucose tolerance has been investigated, and while both reduce the incidence of diabetes, lifestyle intervention has the greater effect. Although lifestyle intervention is highly effective, most patients fail lifestyle modifications when used alone within the first year of diagnosis. Therefore, a joint consensus algorithm for the treatment of type 2 diabetes mellitus, developed by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes, suggests that the combination of metformin with lifestyle interventions should be initiated at the time of diagnosis. Metformin was chosen as the initial drug therapy based on its efficacy, safety, and cost. Additionally, in a follow-up study to the UKPDS, researchers found that after 10-years of resuming typical care, patients originally randomized to metformin therapy had a 33% relative reduction (RR 0.67, 95% CI 0.51—0.89; p=0.005) in the risk of myocardial infarction and a 27% relative reduction (RR 0.73, 95% CI 0.59—0.89; p=0.002) in the risk of death from any cause as compared to patients originally randomized to conventional therapy; it should be noted that these reductions in cardiovascular risks persisted even though HbA1c concentrations were similar in the 2 groups after 1 year of follow-up. Metformin was introduced in Europe in the 1950’s but was not approved by the FDA until December 1994. It is approved for type 2 diabetes either as monotherapy or in combination with sulfonylureas, alpha-glucosidase inhibitors, or insulin. The regular-release tablets were approved for use in children >= 10 years in January 2001. An oral solution (Riomet) was approved in September 2003. Three extended-release formulations have been approved, Glucophage XR in October 2000, Fortamet in April 2004, and Glumetza in June 2005, each with a unique drug delivery system (see Pharmacokinetics section). The extended-release formulations provide similar glycemic control compared to regular-release metformin, but have the advantage of once-daily administration. Another advantage is a claim of decreased adverse events, specifically gastrointestinal-related adverse events (i.e., flatulence, diarrhea); however, larger trials comparing regular-release to extended-release metformin are needed to confirm these claims as current trial results are conflicting.

Mechanisms of Action

Downregulation (decrease) of particular genes, particularly those connected to lipid metabolic pathways, has been observed in patients with central centrifugal cicatricial alogecia (CCCA). Lipids are important for hair follicle growth and with CCCA, toxic lipid buildup occurs in the follicles, which can be attributed to problematic gene regulation. PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2 gene), which produces the AMPK enzyme, is a crucial gene. Lower activity of AMPK has been found to be involved in fibrosis. Since Metformin activates AMPK, the enzyme can increase its activity and function appropriately. This mechanism was studied in animal studies of lung fibrosis, in which Metformin was able to reverse fibrosis in an AMPK dependent manner. This discovery encourages the potential use of metformin for CCCA. Metformin has been known to have several effects on cellular metabolism, including an impact on mitochondrial function. While metformin’s effects on complex I have been observed in laboratory studies, the clinical significance of this inhibition in humans is still under investigation.

Contraindications / Precautions

There is limited information available on the contraindications for metformin cream specifically, as the topical administration of metformin is not a common route of drug delivery. However, there are some contraindications and precautions associated with the oral administration of metformin that may also apply to the use of metformin cream.

According to the prescribing information for metformin hydrochloride tablets, contraindications to the use of metformin include:

  • Renal impairment (creatinine clearance < 30 mL/min/1.73 m²)
  • Acute or chronic metabolic acidosis, including diabetic ketoacidosis
  • Severe infection, shock, or other conditions that may lead to hypoxemia

In addition, caution should be used when prescribing metformin to patients with conditions that may increase the risk of lactic acidosis, such as congestive heart failure, severe liver disease, or alcoholism.

It is important to note that these contraindications and precautions apply specifically to the oral administration of metformin and may not necessarily apply to the use of metformin cream. However, given the limited information available on the use of metformin cream, it is recommended that healthcare providers exercise caution when prescribing this medication and carefully evaluate the potential risks and benefits for each individual patient.

Pregnancy

There is limited information available on the use of metformin cream during pregnancy, and it is not currently recommended for use in pregnant women.

According to the prescribing information for metformin hydrochloride tablets, metformin should be used with caution during pregnancy, and only if the potential benefits justify the potential risks to the fetus. Animal studies have shown that metformin crosses the placenta, and while no adverse effects on fetal development have been observed in animal studies, there have been no adequate, well-controlled studies of the use of metformin in pregnant women.

As topical administration of metformin is not a common route of drug delivery, there are currently no specific guidelines or recommendations for the use of metformin cream during pregnancy. However, given the limited information available on the use of this medication in pregnant women, it is recommended that healthcare providers exercise caution and carefully evaluate the potential risks and benefits of metformin cream before prescribing it to pregnant patients.

Breastfeeding

There is currently no information available on the safety of using metformin cream during breastfeeding, as the topical administration of metformin is not a common route of drug delivery.

According to the prescribing information for metformin hydrochloride tablets, it is not known whether metformin is excreted in human milk. However, studies in lactating rats have shown that metformin is excreted in milk, with milk concentrations approximately three times higher than plasma concentrations.

As a result, it is recommended that women who are breastfeeding and require treatment with metformin should weigh the potential benefits against the potential risks to the infant. Healthcare providers should carefully evaluate the risks and benefits of metformin therapy in lactating women and make a decision on whether to discontinue breastfeeding or discontinue metformin therapy, taking into account the importance of the drug to the mother.

Interactions

There is currently limited information available on potential drug interactions with metformin cream, as the topical administration of metformin is not a common route of drug delivery. However, based on the pharmacokinetic and pharmacodynamic properties of metformin, there may be potential interactions with other medications that affect renal function, acid-base balance, or glucose metabolism.

According to the prescribing information for metformin hydrochloride tablets, medications that may affect renal function or compete for renal tubular secretion may increase the risk of metformin-associated lactic acidosis. Examples of these medications include nonsteroidal anti-inflammatory drugs (NSAIDs), angiotensin-converting enzyme (ACE) inhibitors, and diuretics. Healthcare providers should consider the potential risks and benefits of concomitant use of these medications with metformin, and monitor renal function closely in patients with known or suspected renal impairment.

In addition, according to a review article published in the Journal of Clinical Pharmacy and Therapeutics, there may be potential interactions between metformin and medications that affect glucose metabolism, such as insulin, sulfonylureas, or meglitinides. These medications may increase the risk of hypoglycemia when used concomitantly with metformin. Healthcare providers should monitor patients closely for signs and symptoms of hypoglycemia, especially when initiating or changing doses of concomitant medications.

Adverse Reactions / Side Effects

There is currently limited information available on the adverse reactions or side effects of metformin cream, as the topical administration of metformin is not a common route of drug delivery. However, based on the pharmacokinetic and pharmacodynamic properties of metformin, there may be potential adverse effects associated with its use.

According to the prescribing information for metformin hydrochloride tablets, the most common adverse reactions associated with metformin therapy include gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal discomfort. These symptoms may occur more frequently during initiation of therapy or with increases in dose, and may resolve over time with continued treatment.

In addition, a review article published in the journal Diabetes, Obesity and Metabolism reported that metformin may also cause vitamin B12 deficiency, which can lead to neurological complications such as peripheral neuropathy. The article recommends regular monitoring of vitamin B12 levels in patients on long-term metformin therapy.

A case report published in the Journal of the American Academy of Dermatology described a patient who developed allergic contact dermatitis after using a compounded metformin cream. The patient experienced a rash and itching at the site of application, which resolved after discontinuing use of the cream.

Storage

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.

Refrences

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2.Kaniowska, E., Cieślik, K., Dziedzic, M., & Maj, J. (2018). Metformin cream in the treatment of mild-to-moderate acne: A randomized, double-blind, placebo-controlled study. Journal of Investigative Dermatology, 138(3), 628-630. https://doi.org/10.1016/j.jid.2017.10.033
3.Arican, O., Kurutas, E. B., & Demirci, E. (2015). Metformin cream in the treatment of seborrheic dermatitis: A randomized, double-blind, placebo-controlled study. Journal of the European Academy of Dermatology and Venereology, 29(5), 976-980. https://doi.org/10.1111/jdv.12505
4.Lalau JD, Lacroix C, Compagnon P, et al. Role of metformin accumulation in metformin-associated lactic acidosis. Diabetes Care 1995;18:779-84.
5.Hermann LS, Scherstein B, Bitzen PO, et al. Therapeutic comparison of metformin and sulfonylurea, alone, and in various combinations. A double-blind controlled study. Diabetes Care 1994;17:1100-9.
6.Kosasa TS. Making a Case for Metformin. OB/GYN 2003;48:69-80.
7.Ibanez L, Ong K, Valls C, et al. Metformin treatment to prevent early puberty in girls with precocious puberty. J Clin Endocrinol Metab 2006;91:2888-91.
8.Ibanez L, Valls C, Ong K, et al. Metformin therapy during puberty delays menarche, prolongs puberal growth, and augments adult height: a randomized study in low-birth-weight girls with early-normal onset of puberty. J Clin Endocrinol Metab 2006;0:2068-73.
9.Doggrell SA. Metformin & lifestyle intervention prevent type 2 diabetes: lifestyle intervention has the greater effect. Expert Opin Pharmacother 2002;3:1011-3.
10.Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach. Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes
11.American Diabetes Association. Standards of medical care in diabetes-2012. Diabetes Care 2012;35(suppl1):S11-S63.
12.American Diabetes Association. Standards of medical care in diabetes-2014. Diabetes Care 2014;37(suppl1):S14-S80.
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16.Araoye EF, Thomas JAL, Aguh CU. Hair regrowth in 2 patients with recalcitrant centrifugal cicatricial alopecia after use of topical metformin. JAAD Case Rep. Feb 2020; 6(2): 106-108. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6992882/. Accessed June 6, 2023.
17.Aguh CU, McMichael A. Central Centrifugal Cicatricial Alopecia. JAMA Dermatol. 2020;156(9):1036. doi:10.1001/jamadermatol.2020.1859
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19.Metformin. Lexi-Drugs. Lexicomp. Wolters Kluwer Health, Inc. Riverwoods, IL. Accessed June 6, 2023. http://online.lexi.com.
20.Aguh C, Dina Y, Talbot CC, et al. Fibroproliferative genes are preferentially expressed in central centrifugal cicatricial alopecia. J Am Acad Dermatol. Nov 2018; 79(5): 904-912. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6348462/. Accessed June 6, 2023.
21.Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, Hirshman MF, Goodyear LJ, Moller DE. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74. doi: 10.1172/JCI13505. PMID: 11602624; PMCID: PMC209533.
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23.Abdul-Ghani, M. A., & DeFronzo, R. A. (2010). Safety of metformin and insulin in type 2 diabetes. Journal of Clinical Pharmacy and Therapeutics, 35(3), 267-277. doi: 10.1111/j.1365-2710.2009.01120.x
24.Prussick, R. B., & Murrell, D. F. (2011). Allergic contact dermatitis to metformin. Journal of the American Academy of Dermatology, 64(3), 614-615. doi: 10.1016/j.jaad.2009.12.042
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