Is metformin (biguanide oral hypoglycemic agent) used for weight loss?

From the Guidelines

Metformin can be used for weight loss, particularly in patients with insulin resistance, prediabetes, or polycystic ovary syndrome (PCOS), with approximately 3% weight loss and 25% to 50% of participants achieving at least 5% weight loss, as seen in a 2023 study published in JAMA 1. The use of metformin for weight loss is not FDA-approved, but it may cause modest weight reduction as a side effect when used for its primary indication of treating type 2 diabetes. Some key points to consider when using metformin for weight loss include:

• Typical weight loss with metformin averages 2-3% of body weight
• Dosing typically starts at 500mg once daily with meals, potentially increasing to 1000-2000mg daily divided into two doses
• Metformin works by reducing hepatic glucose production, improving insulin sensitivity, and decreasing intestinal glucose absorption
• The weight loss effect may result from reduced appetite, improved insulin function, and changes in gut microbiota
• Common side effects include gastrointestinal disturbances like diarrhea and nausea
• Metformin should not replace lifestyle modifications such as diet and exercise, which remain the cornerstone of weight management
• Patients should only use metformin for weight loss under medical supervision, as it's not appropriate for everyone and requires monitoring for potential side effects and contraindications, as noted in a 2023 review of obesity management in adults 1. Additionally, metformin has been shown to have beneficial effects on A1C, weight, and cardiovascular mortality compared to sulfonylureas, as seen in a 2020 study published in Diabetes Care 1. It's also important to note that metformin is effective and safe, is inexpensive, and may reduce risk of cardiovascular events and death, as stated in a 2023 study published in Diabetes Care 1. However, the principal side effects of metformin are gastrointestinal intolerance due to bloating, abdominal discomfort, and diarrhea, which can be mitigated by gradual dose titration, as noted in a 2020 study published in Diabetes Care 1. Overall, metformin can be a useful tool for weight loss in certain patients, but it should be used under medical supervision and in conjunction with lifestyle modifications.

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.

Metformin may be associated with weight loss in some patients, as evidenced by the mean change in body weight in the clinical trials. However, the weight loss is generally mild and may not be significant in all cases. In one study, the metformin arm had a mean change in body weight of -8.4 lbs, while in another study, the mean change was -1.4 lbs and -3.3 lbs, respectively. The placebo arm also had a mean change in body weight of -2.4 lbs and -2.0 lbs, respectively. Therefore, while metformin may be associated with some weight loss, it is not a primary indication for the medication, and the weight loss effects may be variable 2.

• Key points:
  • Metformin may be associated with mild weight loss
  • Weight loss effects may be variable
  • Not a primary indication for metformin

From the Research

Metformin and Weight Loss

• Metformin, a biguanide oral hypoglycemic agent, has been found to have multiple benefits for health beyond its anti-hyperglycemic properties, including weight loss 3.
• Large cohort studies have shown weight loss benefits associated with metformin therapy, with mechanisms underlying this effect 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 3.
• Metformin has been used for the treatment of obesity, with studies showing that it can induce weight loss by mitigating insulin resistance in the hypothalamic pro-opiomelanocortin neurons, stimulating the enteral release of glucagon-like peptide 1, and inducing favorable changes to enteric microbiota 4.

Clinical Use of Metformin for Weight Loss

• Metformin is widely considered to be the optimal initial therapy for patients with type 2 diabetes mellitus, and has been found to have a weight-neutral effect, with some studies showing improvements in weight loss 5.
• A retrospective cohort study found that metformin monotherapy resulted in similar weight loss outcomes 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 6.
• Metformin's effects on weight loss are thought to be due to its ability to reduce hunger, enhance satiety, and induce favorable changes to enteric microbiota, making it a potential treatment option for obesity 4.

Benefits of Metformin for Weight Loss

• Metformin has been found to have several benefits for weight loss, including reducing insulin resistance, improving glucose metabolism, and inducing weight loss without increasing the risk of hypoglycemia 7.
• Metformin's weight loss effects are also thought to be due to its ability to activate adenosine monophosphate-activated kinase (AMPK), which enhances cellular energy production and endothelial nitric oxide synthase-mediated vascular relaxation 4.
• Overall, metformin has been found to be a safe and effective treatment option for weight loss, with several studies showing its potential benefits for obesity and related metabolic disorders 3, 4, 6.