Is metformin (Metformin Hydrochloride) effective for weight gain associated with antipsychotic medication use?

From the Guidelines

Metformin should be considered as an adjunctive therapy for managing weight gain associated with antipsychotic use, with a typical dose of 1000 mg total daily dose, as it has been shown to counteract the effects of weight gain-promoting agents, particularly antipsychotics, with a mean difference of −3.27 kg (95% CI, −4.66 kg to −1.89 kg) 1. When prescribing metformin for this purpose, it's essential to counsel patients on the risk of weight gain, discuss lifestyle modifications, and monitor weight trajectory, as well as metabolic parameters and vitamin B12 levels.

• Metformin works by reducing hepatic glucose production, improving insulin sensitivity, and potentially decreasing food intake through effects on gut hormones.
• It's most effective when combined with lifestyle modifications like diet and exercise.
• Common side effects include gastrointestinal disturbances (nausea, diarrhea), which can be minimized by starting with a low dose and taking with food.
• Metformin is contraindicated in patients with significant renal impairment (eGFR <30 mL/min), severe liver disease, or acute conditions that may affect kidney function.
• Before starting treatment, baseline kidney function, liver function, and vitamin B12 levels should be assessed, with regular monitoring throughout therapy, as supported by recent studies 1. Key considerations for metformin use in this context include:
• Doses greater than 1500 mg may be associated with greater weight loss, but the typical dose of 1000 mg total daily dose has been shown to be effective in counteracting weight gain associated with antipsychotic use 1.
• Metformin's pleiotropic effects, including decreased inflammation, increased insulin and leptin sensitivity, and decreased hunger and ghrelin levels, especially with twice-daily dosing, may also contribute to its effectiveness in managing weight gain associated with antipsychotic use 1.

From the Research

Metformin for Weight Gain Related to Antipsychotic Use

• Metformin has been studied as a potential treatment for weight gain related to antipsychotic use, with some studies suggesting its effectiveness in preventing and treating antipsychotic-induced weight gain 2, 3, 4.
• The mechanism of metformin in causing weight loss is peripheral, and it has been shown to be generally well-tolerated, with some studies suggesting its use in pediatric patients 2.
• A network meta-analysis of pharmacological interventions for antipsychotic-induced weight gain found that metformin 750 mg with lifestyle modification was the most effective treatment, followed by topiramate 200 mg, metformin 750 mg, and topiramate 100 mg 5.
• Another study suggested that initiating metformin early in the course of antipsychotic treatment, particularly in young and healthy patients, may help minimize weight gain 4.
• The use of metformin for weight gain related to antipsychotic use is supported by several studies, which suggest that it may be an effective option for patients who have failed lifestyle and dietary changes 2, 3, 4, 5.

Comparison with Other Treatments

• Metformin has been compared to other treatments for antipsychotic-induced weight gain, including topiramate, sibutramine, and liraglutide, with varying results 5.
• A systematic review and meta-analysis found that all antipsychotics led to significantly more weight gain, and most antipsychotics led to a significantly higher risk for a clinically relevant weight gain of ≥7% compared to placebo 6.
• The choice of treatment for antipsychotic-induced weight gain should be based on individual patient needs and circumstances, taking into account the potential benefits and risks of each treatment option 3, 5.

Clinical Implications

• The use of metformin for weight gain related to antipsychotic use has important clinical implications, including the potential to improve treatment adherence and reduce the risk of metabolic and cardiovascular complications 2, 3, 4.
• Clinicians should consider the potential for weight gain when prescribing antipsychotics and monitor patients regularly for changes in weight and metabolic parameters 6.
• Early intervention with metformin or other treatments may be necessary to prevent or minimize weight gain in patients at high risk 4, 5.