What is the effect of Metformin (metformin hydrochloride) on weight loss?

From the Guidelines

Metformin can promote modest weight loss in some individuals, particularly those with insulin resistance or type 2 diabetes, with a typical weight loss of approximately 3% of body weight over 6-12 months, as seen in a recent study published in 2023 1. The weight loss effect of metformin is thought to be due to its ability to reduce glucose production in the liver, improve insulin sensitivity, and potentially decrease appetite and caloric intake.

• The typical weight loss dose ranges from 1000-2000mg daily, usually divided into two doses with meals.
• Metformin may also alter gut microbiota in ways that support weight management.
• Side effects can include gastrointestinal issues like diarrhea, nausea, and abdominal discomfort, which typically improve over time.
• Starting with a low dose (500mg daily) and gradually increasing can help minimize these effects.
• While metformin is FDA-approved for diabetes treatment, its use for weight loss alone is considered off-label.
• It's most effective when combined with lifestyle modifications including diet and exercise, and works best in those with insulin resistance.
• Patients should maintain adequate hydration and vitamin B12 levels while taking metformin, as the medication can affect B12 absorption with long-term use, as noted in a study published in 2023 1.
• A meta-analysis of 5 studies that used metformin in children and adolescents reported a placebo-subtracted reduction in BMI of 1.42 kg/m², as seen in a study published in 2013 1.
• Doses of metformin greater than 1500 mg are associated with the greatest weight loss, as reported in a study published in 2023 1.

From the FDA Drug Label

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 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 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. Mean change in body weight from baseline to week 24 was 0.9 lbs, 1.1 lbs and 0.9 lbs, respectively.

Weight Loss Effect of Metformin

• The studies show a variable effect of metformin on weight loss, with some studies showing a slight decrease in body weight and others showing little to no change.
• In one study, the mean change in body weight from baseline to week 29 was -1.4 lbs in the metformin arm, compared to -2.4 lbs in the placebo arm 2.
• Another study showed a mean change in body weight of -8.4 lbs in the metformin arm, compared to 0.9 lbs in the metformin/glyburide arm and -0.7 lbs in the glyburide arm 2.
• A pediatric study showed a mean change in body weight of -3.3 lbs in the metformin arm, compared to -2.0 lbs in the placebo arm 2.
• Overall, the evidence suggests that metformin may have a slight weight loss effect, but the results are inconsistent and not always statistically significant.

From the Research

Effect of Metformin on Weight Loss

• Metformin has been found to have a positive effect on weight loss in patients with or without type 2 diabetes 3, 4, 5.
• Studies have shown that metformin can lead to significant weight reduction in overweight or obese individuals, although the trials were often limited by small patient populations and weak design 3.
• The weight loss effects of metformin appear to be similar in patients with or without type 2 diabetes/prediabetes, with average weight loss ranging from 6.5% to 7.4% of baseline weight over 6-12 months 4.
• Metformin's mechanisms for inducing weight loss are thought to include 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 6.
• Metformin is considered a weight-neutral or weight-sparing treatment, which constitutes a therapeutic advantage in diabetes management where other first-line oral antidiabetic treatments often promote clinically significant weight gain 7, 5.

Metformin's Weight Loss Outcomes

• Categorical weight losses (≥5% and ≥10% of baseline weight) were found to be similar in patients with or without type 2 diabetes/prediabetes treated with metformin monotherapy 4.
• Metformin has been shown to mitigate the adverse effects of insulin on body weight, and its use is associated with a lower cardiovascular mortality compared with sulfonylurea therapy 7, 5.
• Large cohort studies have demonstrated weight loss benefits associated with metformin therapy, and metformin is being explored in the management of obesity's sequelae such as hepatic steatosis, obstructive sleep apnea, and osteoarthritis 6.