From the Guidelines
Metformin should be prescribed off-label for weight loss at doses greater than 1500 mg, as this is associated with the greatest weight loss, with approximately 3% weight loss and 25-50% of participants achieving at least 5% weight loss, as seen in recent studies 1. When prescribing metformin for weight loss, it's essential to consider the potential benefits and risks. The medication can be started at a low dose, such as 500 mg once daily with a meal, and gradually increased to 500 mg twice daily if tolerated, with a maximum of 2000 mg daily divided into two doses. Some key points to consider when prescribing metformin for weight loss include:
- The medication should be taken with meals to minimize gastrointestinal side effects like nausea, diarrhea, and abdominal discomfort.
- Weight loss results are modest, typically 2-5% of body weight over 6-12 months.
- Metformin works by reducing glucose production in the liver, improving insulin sensitivity, and potentially decreasing appetite and caloric intake.
- It's most effective when combined with lifestyle modifications including diet and exercise.
- Patients should be aware that metformin takes time to show results, requires medical supervision, and may not be suitable for everyone, particularly those with kidney disease, liver disease, or alcohol use disorder.
- Regular monitoring of kidney function is necessary while taking this medication, as metformin is contraindicated in patients with severe renal impairment 1. The most recent and highest quality study on this topic, published in 2023 in the Journal of the American Medical Association (JAMA), found that metformin was associated with significant weight loss, particularly at doses greater than 1500 mg 1.
From the FDA Drug Label
2 DOSAGE AND ADMINISTRATION
- 1 Adult Dosage Metformin Hydrochloride Tablets The recommended starting dose of metformin hydrochloride tablets are 500 mg orally twice a day or 850 mg once a day, given with meals. Increase the dose in increments of 500 mg weekly or 850 mg every 2 weeks on the basis of glycemic control and tolerability, up to a maximum dose of 2550 mg per day, given in divided doses.
The dose of metformin for weight loss is not explicitly stated in the drug label. The label only provides dosage information for glycemic control.
- The recommended starting dose is 500 mg orally twice a day or 850 mg once a day.
- The maximum dose is 2550 mg per day, given in divided doses. However, since the label does not directly address weight loss, no conclusion can be drawn about the dose for this specific indication 2.
From the Research
Metformin Dosage for Weight Loss
- The dosage of metformin for weight loss is not explicitly stated in the provided studies, but the effective dosage for weight loss in non-diabetic individuals with obesity was up to 2,500 mg per day 3.
- In the study of women with polycystic ovary syndrome (PCOS), metformin was administered at a dosage of 500 mg three times daily 4.
- Another study used metformin 850 mg twice daily for 6 months in normal weight patients with PCOS 5.
Weight Loss Outcomes with Metformin
- Metformin has been shown to be effective in reducing weight in non-diabetic individuals with obesity, with a mean weight loss of 5.8 ± 7.0 kg (5.6 ± 6.5%) over 6 months 3.
- In women with PCOS, metformin was associated with lower BMI and subcutaneous adipose tissue, and improved menstruation compared to lifestyle modification alone 6.
- Metformin has also been shown to reduce insulin resistance and improve metabolic outcomes in individuals with PCOS 4.
Mechanisms of Metformin-Induced Weight Loss
- Metformin's effects on weight loss are thought to be due to multiple mechanisms, including reduction in hepatic gluconeogenesis, reduction in insulin production, modulation of hypothalamic appetite regulatory centers, alteration in the gut microbiome, and reversal of consequences of aging 7.
- Metformin may also have benefits beyond weight loss, including improvement in hepatic steatosis, obstructive sleep apnea, and osteoarthritis 7.