Can metformin (metformin hydrochloride) aid in weight loss?

From the Guidelines

Metformin can help with weight loss, as evidenced by the most recent and highest quality study 1, which suggests that metformin is effective in reducing body weight and improving plasma lipid profiles.

Key Points

• Metformin is typically used as a first-line medication for type 2 diabetes and often leads to modest weight loss of about 2-3% of body weight 1.
• The standard dosing starts at 500 mg once or twice daily with meals, potentially increasing to a maximum of 2000-2500 mg daily divided into two doses.
• The weight loss effect occurs through several mechanisms: metformin reduces appetite by affecting hunger hormones, decreases sugar absorption in the intestines, improves insulin sensitivity, and may alter gut bacteria in ways that support weight management 1.
• Side effects can include gastrointestinal issues like diarrhea, nausea, and stomach pain, which typically improve over time 1.
• While metformin is sometimes prescribed off-label for weight management in non-diabetic patients with obesity or insulin resistance, lifestyle modifications including diet and exercise remain essential components of any weight loss plan involving this medication 1.

Mechanism of Action

• Metformin reduces appetite by affecting hunger hormones 1.
• Metformin decreases sugar absorption in the intestines 1.
• Metformin improves insulin sensitivity 1.
• Metformin may alter gut bacteria in ways that support weight management 1.

Important Considerations

• Metformin is contraindicated in patients with impaired kidney function, decreased tissue perfusion or hemodynamic instability, liver disease, alcohol abuse, heart failure, and any condition that might lead to lactic acidosis 1.
• The occurrence of lactic acidosis is now known to be very rare, and metformin may be safely used in patients with reduced estimated glomerular filtration rates (eGFR) 1.

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 and Weight Loss:

• In some studies, metformin was associated with a mean change in body weight of -1.4 lbs, -8.4 lbs, and -3.3 lbs compared to placebo or other treatments.
• However, the mean change in body weight was not always significant, and in some cases, the change was small or not statistically significant.
• The evidence suggests that metformin may be associated with weight loss in some patients, but the effect is not consistent across all studies.
• It is essential to note that metformin is not approved for weight loss, and its primary indication is for the treatment of type 2 diabetes mellitus.
• Patients should consult their healthcare provider to discuss the potential benefits and risks of metformin treatment, including its effects on body weight 2, 2, 2.

From the Research

Metformin and Weight Loss

• Metformin has been shown to have multiple benefits for health beyond its anti-hyperglycemic properties, including weight loss benefits associated with metformin therapy 3.
• The mechanisms underlying metformin's effects on obesity 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 3.
• Emerging evidence suggests that metformin-associated weight loss is due to decreased food intake, which is the primary weight loss mechanism, and changes in hypothalamic physiology, including leptin and insulin sensitivity 4.
• Metformin induces modest weight loss in overweight and obese individuals at risk for diabetes, and a more detailed understanding of how metformin induces weight loss may lead to optimal co-prescription of lifestyle modification with pharmacology for the treatment of obesity independent of diabetes 4.

Metformin's Effects on Insulin Sensitivity and Glucose Metabolism

• Metformin enhances insulin sensitivity, and its mechanism of action remains elusive, but it is used to prevent and treat diabetes 5.
• Metformin reduces post-prandial plasma glucose, suggesting that the drug facilitates glucose storage as hepatic glycogen after meals, and replenishment of glycogen store attenuates the accelerated rate of gluconeogenesis and reduces both glycogen cycling and hepatic glucose output 5.
• Metformin also reduces fasting hyperglycemia due to declining hepatic glucose production, and decreases the amount of insulin required for metabolic control in patients with diabetes, reflecting improvement of insulin activity 5.
• Metformin increases insulin sensitivity and basal glucose clearance in type 2 (non-insulin dependent) diabetes mellitus, and improves efficiency of glucose utilisation, both basally and under conditions of euglycaemic hyperinsulinaemia 6.

Clinical Use of Metformin

• Metformin is one of the oldest antidiabetic medications, commonly used in the management of type 2 diabetes, and its mechanism of action is based on reducing glucose production in the liver, decreasing insulin resistance, and increasing insulin sensitivity 7.
• According to current guidelines, metformin can be used as the first‑line agent in the management of diabetes, but in individuals with type 2 diabetes who would benefit from cardio‑renal protection, newer agents are favored as the first‑line therapy 7.