Is metformin (metformin hydrochloride) used for weight loss?

From the Guidelines

Metformin is associated with approximately 3% weight loss and can be used off-label for weight management, particularly in patients with insulin resistance, prediabetes, or polycystic ovary syndrome (PCOS), as evidenced by a recent study published in JAMA in 2023 1.

Key Points

• Metformin is not officially approved for weight loss, but it may cause modest weight reduction as a side effect when used for its primary purpose of treating type 2 diabetes.
• The weight loss effect of metformin is generally modest, with approximately 25% to 50% of participants achieving at least 5% weight loss, and doses greater than 1500 mg are associated with the greatest weight loss 1.
• Metformin works by reducing glucose production in the liver, improving insulin sensitivity, and decreasing intestinal absorption of carbohydrates.
• Some healthcare providers may prescribe metformin "off-label" for weight management, particularly in patients with insulin resistance, prediabetes, or polycystic ovary syndrome (PCOS).
• Metformin should only be used under medical supervision as it can cause side effects including gastrointestinal issues like diarrhea, nausea, and abdominal discomfort.

Considerations

• For dedicated weight loss, lifestyle modifications including diet and exercise remain the first-line approach, with FDA-approved weight loss medications being more appropriate options when pharmacological intervention is needed.
• The American College of Physicians recommends metformin as the initial pharmacologic therapy for type 2 diabetes due to its effectiveness in reducing glycemic levels, aiding in weight loss, and reducing LDL cholesterol and triglyceride levels 1.
• A study published in Diabetes Care in 2002 found that metformin reduced the risk of developing type 2 diabetes by 31% in individuals with impaired glucose tolerance 1.

Recommendations

• Metformin can be considered for off-label use in weight management, particularly in patients with insulin resistance, prediabetes, or polycystic ovary syndrome (PCOS), under medical supervision and with careful monitoring of side effects.
• Lifestyle modifications, including diet and exercise, should remain the first-line approach for dedicated weight loss.
• FDA-approved weight loss medications should be considered when pharmacological intervention is needed for weight loss.

From the FDA Drug Label

Mean baseline body weight was 201 lbs and 206 lbs in the metformin hydrochloride tablets and placebo arms, respectively. Mean change in body weight from baseline to week 29 was -1.4 lbs and -2. 4 lbs in the metformin hydrochloride tablets and placebo arms, respectively. Mean baseline body weight was 202 lbs, 203 lbs, and 204 lbs in the metformin hydrochloride tablets /glyburide, glyburide, and metformin hydrochloride tablets arms, respectively. Mean change in body weight from baseline to week 29 was 0.9 lbs, -0.7 lbs, and -8. 4 lbs in the metformin hydrochloride tablets /glyburide, glyburide, and metformin hydrochloride tablets arms, respectively. Mean baseline body weight was 205 lbs and 189 lbs in the metformin hydrochloride tablets and placebo arms, respectively. Mean change in body weight from baseline to week 16 was -3.3 lbs and -2. 0 lbs in the metformin hydrochloride tablets and placebo arms, respectively.

Metformin is not primarily used for weight loss. Although some studies show a mean change in body weight, the primary indication of metformin is for the treatment of type 2 diabetes mellitus. The changes in body weight observed in the studies are likely secondary effects and not the primary intention of the treatment. Therefore, metformin should not be used solely for weight loss purposes without considering its primary indication and potential side effects 222.

From the Research

Metformin and Weight Loss

• Metformin is used for weight loss in various contexts, including obesity and polycystic ovarian syndrome 3
• A systematic review found that metformin treatment for ≥6 months resulted in significant weight loss in adults with obesity, with an average reduction in weight/BMI 4
• Studies have shown that metformin is 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 5
• A double-blind, randomized, controlled trial found that metformin resulted in statistically significant reductions in BMI and insulin resistance in obese women at midlife 6
• A retrospective cohort study found that metformin-induced weight loss was similar in patients with or without type 2 diabetes/prediabetes, with average weight loss of 6.5% and 7.3% at 6 and 12 months, respectively 7

Key Findings

• Metformin has been shown to be effective in reducing weight in various populations, including adults and children with obesity 4, 5
• The degree of weight loss achieved with metformin varies, but average reductions in weight/BMI range from 5-10% 4, 5, 6, 7
• Metformin has been found to improve insulin sensitivity and reduce the progression to type 2 diabetes in adults with obesity 4, 6