Day: August 18, 2025

What Are Possible Uses for Metformin?

Patient Presentation
A 12-year-old female came to clinic for her health maintenance examination. She had been well overall. She had menarche about 10 months previously and had had three periods of time where she had had bleeding for 3 weeks. The last time only stopped with hormonal intervention. She had been at the 95% for weight last year and had increased her body mass index significantly over the subsequent year. The previous year she had had some abdominal striae but did not have any acanthosis nigricans. Laboratory testing for obesity, insulin resistance, and thyroid disease were negative last year.

The past medical history was otherwise negative. Her review of systems was negative for sleeping problems including snoring, problems with fatigue, headache, musculoskeletal problems, or bruising or bleeding.

The pertinent physical exam showed normal vital signs. Her BMI was 36.2 (~120% for the usual 95%). Her blood pressure was 110/74. Her skin examination showed acanthosis nigricans at her neck and truncal striae. She had increased general hair on her body that looked to be consistent with the family and her genetic background. The rest of her examination was normal.

The diagnosis of a healthy female with increased obesity, abnormal menstrual bleeding and acanthosis nigricans was made. Polycystic ovarian syndrome (PCOS) was considered. Her hemoglobin A1c was 5.7%, she had increased triglycerides, HDL and LDL cholesterol on fasting sample. Testosterone was normal as was testing for bleeding disorders.

The patient’s clinical course showed that she was able to see an endocrinologist who felt that she was likely at risk for PCOS but at this time could not make that diagnosis. She did have increased obesity, dyslipidemia and insulin resistance. She was started on metformin, life-style changes and had nutritional counseling. She was to followup in 6 months.

Discussion
Metformin (1,1-dimethylbiguanide), while not perfect, is a pretty good medication. It has been in use in the United Kingdom since 1958 and in the United States since 1995. It is considered a generally safe drug. It is inexpensive, orally absorbed, not metabolized by the liver, and is not highly protein bound. It does not cause hypoglycemia. It is excreted unchanged mainly through the kidney, therefore patients with renal failure need to be monitored closely. Side effects include nausea and emesis (which are much improved when taken with a meal). Lactic acidosis is rare (incidence 1 in 30,000). Metformin can cause decreased B12 levels as well. Monitoring of pre- and post-prandial glucoses, Hemoglobin A1c, renal function and B12 levels are recommended at intervals.

Metformin, by several interactions but mainly by activating AMP-activated protein kinase (AMPK) causes:

  • Decreases glucose intestinal absorption
  • Decreases hepatic gluconeogenesis
  • Opposes glucagon
  • Increases whole-body insulin sensitivity though increased insulin activity

Patients (50-70%) with PCOS have insulin resistance and metformin is a common medication used for this. Additionally metformin also has favorable effects on sex hormones and sex-hormone binding globulin which also helps treat the oligomenorrhea of PCOS. A review of PCOS and its potential health problems can be found here.

Learning Point
Indications and common off label uses of metformin include:

  • Type 2 diabetes mellitus (T2DM) – first line therapy
  • Prediabetes
  • Type 1 diabetes mellitus – not for treatment but sometimes is used as adjuvant therapy
  • Gestational diabetes
  • PCOS
  • Weight gain issues due to antipsychotic medications

Other potential uses:

  • Anti-cancer properties for decreased risk of cancer overall and particular gastointestinal and genital cancers
  • Anti-aging
  • Cardiovascular protective agent
  • Neuroprotective agent – uses with dementia and psychiatric disease
  • Liver disease – metabolic dysfunction-associated steatotic

Use of metformin for obesity and weight reduction has positive effect but data only shows small effects. A 2016 Cochrane systematic review concluded “…that pharmacological interventions (metformin, sibutramine, orlistat and fluoxetine) may have small effects in reduction in BMI and obesity in obese children and adolescents. The review notes that many of the drugs are not licensed for this indication, some of the drugs have been withdrawn, and many of the studies are of low quality.” A 2021 systematic review concluded “…that metformin has modest but favorable effects on weight and insulin resistance and a tolerable safety profile among children and adolescents with obesity.” The authors note that the “”…evidence is of varying quality, with high heterogeneity between trials….”

Questions for Further Discussion
1. What counseling do you emphasize for patients with obesity?
2. When do you prescribe metformin in your practice and why?
3. What are indications of insulin resistance?

Related Cases

To Learn More
To view pediatric review articles on this topic from the past year check PubMed.

Evidence-based medicine information on this topic can be found at SearchingPediatrics.com and the Cochrane Database of Systematic Reviews.

Information prescriptions for patients can be found at MedlinePlus for these topics: Metabolic Syndrome and PCOS.

To view current news articles on this topic check Google News.

To view images related to this topic check Google Images.

To view videos related to this topic check YouTube Videos.

Mead E, Atkinson G, Richter B, et al. Drug interventions for the treatment of obesity in children and adolescents. Cochrane Database Syst Rev. 2016. Accessed April 15, 2025.

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

Masarwa R, Brunetti VC, Aloe S, Henderson M, Platt RW, Filion KB. Efficacy and Safety of Metformin for Obesity: A Systematic Review. Pediatrics. 2021;147(3):e20201610. doi:10.1542/peds.2020-1610

Karavanaki K, Paschou SA, Tentolouris N, Karachaliou F, Soldatou A. Type 2 diabetes in children and adolescents: distinct characteristics and evidence-based management. Endocrine. 2022;78(2):280-295. doi:10.1007/s12020-022-03172-y

Corcoran C, Jacobs TF. Metformin. In: StatPearls. StatPearls Publishing; 2025. Accessed April 15, 2025. http://www.ncbi.nlm.nih.gov/books/NBK518983/

Petrie JR. Metformin beyond type 2 diabetes: Emerging and potential new indications. Diabetes Obes Metab. 2024;26 Suppl 3:31-41. doi:10.1111/dom.15756

Author
Donna M. D’Alessandro, MD
Professor of Pediatrics, University of Iowa