From the Research
Metformin is recommended at a dose of 500-1000 mg twice daily to manage clozapine-induced weight gain, with treatment typically beginning with 500 mg once daily with a meal, then gradually increasing to 500 mg twice daily after one week to minimize gastrointestinal side effects. The dose can be further increased to 1000 mg twice daily if needed and tolerated, as supported by a study published in 2022 1. This medication works by improving insulin sensitivity, reducing hepatic glucose production, and potentially decreasing appetite. Some key points to consider when prescribing metformin for clozapine-induced weight gain include:
- Metformin should be taken with meals to reduce stomach upset
- Patients should be monitored for vitamin B12 deficiency with long-term use
- Kidney function should be assessed before starting treatment, as dose adjustments are necessary for patients with renal impairment
- Patients should be aware that metformin may take several weeks to show noticeable effects on weight
- Metformin works best when combined with lifestyle modifications like diet and exercise, as shown in a study published in 2016 2 A study published in 2022 1 demonstrated that co-prescription of clozapine and metformin was associated with less weight gain and related metabolic dysfunction at 6 and 12 months after initiation versus clozapine alone. Another study published in 2016 3 found that metformin was superior to placebo in terms of weight loss and improvement in metabolic parameters, including waist circumference, fasting glucose, and triglycerides. Overall, the current evidence supports the use of metformin at a dose of 500-1000 mg twice daily to manage clozapine-induced weight gain, with careful monitoring and lifestyle modifications to optimize treatment outcomes.