Does metformin (metformin hydrochloride) aid in weight loss?

From the Guidelines

Metformin can help with weight loss, with approximately 3% weight loss and 25-50% of participants achieving at least 5% weight loss, as seen in recent studies 1. The weight loss effect of metformin is thought to be due to its mechanisms of reducing glucose production in the liver, improving insulin sensitivity, and decreasing intestinal absorption of carbohydrates.

• The standard dosing of metformin starts at 500 mg once or twice daily with meals, potentially increasing to a maximum of 2,000-2,500 mg daily divided into two or three doses.
• Doses of metformin greater than 1500 mg are associated with the greatest weight loss, as noted in a recent review 1.
• Metformin’s pleiotropic effects include decreased inflammation, increased insulin and leptin sensitivity, and decreased hunger and ghrelin levels, especially with twice-daily dosing.
• While metformin may support weight loss efforts, it works best when combined with healthy eating habits and regular physical activity rather than as a standalone weight loss solution.
• Common side effects of metformin include gastrointestinal issues like diarrhea, nausea, and abdominal discomfort, which typically improve over time.
• Recent studies have consistently shown that metformin is effective in preventing or delaying the onset of type 2 diabetes, particularly in individuals with prediabetes or a history of gestational diabetes mellitus 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 with Metformin:

• The studies show that metformin can lead to a small decrease in body weight compared to placebo or other treatments.
• However, the magnitude of weight loss varies across studies, and in some cases, the difference between metformin and placebo or other treatments is not significant.
• Overall, metformin may help with weight loss, but the effect is generally modest and may not be consistent across all studies 2.

From the Research

Metformin and Weight Loss

• Metformin has been shown to be effective in reducing weight in both children and adults with obesity, with studies indicating a greater reduction in weight/BMI with metformin compared to placebo 3, 4.
• The effects of metformin on weight/BMI vary, with smaller reductions in children than in adults, which may be due to differences in adherence, daily dosage, and insulin status 3.
• Metformin-induced weight loss is not limited to patients with type 2 diabetes, as studies have shown comparable weight loss outcomes in patients with obesity with or without type 2 diabetes/prediabetes 5.
• The mechanisms underlying metformin's effects on obesity and weight loss are complex and multifaceted, involving modulation of hypothalamic appetite regulatory centers, alteration in the gut microbiome, and reversal of consequences of aging 6.

Studies on Metformin and Weight Loss

• A systematic review of 15 pediatric and 14 adult studies found that metformin significantly reduced weight/BMI in both children and adults, with a greater reduction in weight/BMI observed in adults 3.
• A retrospective cohort study of 222 patients with obesity found that metformin monotherapy resulted in similar weight loss outcomes in patients with or without type 2 diabetes/prediabetes 5.
• A study of 154 consecutive patients with a body mass index ≥27 kg/m2 found that metformin treatment resulted in a mean weight loss of 5.8±7.0 kg (5.6±6.5%) over 6 months, with patients with severe insulin resistance losing significantly more weight than insulin-sensitive patients 4.

Metformin's Role in Obesity Management

• Metformin is considered a first-line therapy for type 2 diabetes and has been shown to be effective in reducing weight and improving insulin sensitivity in patients with obesity 3, 7.
• Metformin's effects on weight loss and obesity management are thought to be due to its ability to reduce hepatic gluconeogenesis, decrease insulin resistance, and increase insulin sensitivity 6, 7.