From the Guidelines
Metformin can be used to mitigate weight gain related to antipsychotic use, as it has been shown to have a positive effect on weight management by reducing appetite and increasing insulin sensitivity.
- The use of metformin for this purpose is considered off-label, but its efficacy and safety profile make it a viable option for patients experiencing antipsychotic-induced weight gain, particularly those taking olanzapine and clozapine.
- Studies have demonstrated that metformin can lead to significant weight loss in patients who have gained weight due to antipsychotic medication, with doses of metformin greater than 1500 mg associated with the greatest weight loss 1.
- Metformin’s pleiotropic effects include decreased inflammation, increased insulin and leptin sensitivity, and decreased hunger and ghrelin levels, especially with twice-daily dosing 1.
- In patients with psychiatric diagnoses, lurasidone and ziprasidone appear to be the most weight-neutral antipsychotic options, while olanzapine, clozapine, quetiapine, and risperidone are consistently associated with weight gain 1.
- When prescribing medications that promote weight gain, clinicians should counsel patients on the risk of weight gain, discuss lifestyle modifications, and monitor weight trajectory 1.
The FDA Drug Labels for metformin (PO) do not address this question.
From the Research
Metformin and Antipsychotic-Induced Weight Gain
- Metformin has been shown to be effective in managing weight gain induced by antipsychotics, particularly in patients with schizophrenia 2, 3, 4.
- A retrospective cohort study found that patients on antipsychotics with metformin had a lower mean weight change (-0.04 kg) compared to those on antipsychotics alone (2.5 kg) 2.
- A meta-analysis of 20 studies with 1070 patients revealed that metformin significantly attenuated weight gain in patients receiving antipsychotics, with a mean weight change of -3.32 kg [95% CI: -4.57 to -2.07] 3.
- Another meta-analysis of 14 studies with 1126 participants found that metformin was superior to placebo in attenuating weight gain (-3.12 kg, 95% CI -4.22 to -2.01 kg) 4.
Effectiveness of Metformin in Different Populations
- Metformin has been shown to be effective in managing antipsychotic-induced weight gain in children and adolescents, with a greater reduction in BMI z score slope observed in non-obese individuals compared to those who were mildly-to-moderately obese or severely obese 5.
- The effectiveness of metformin in managing weight gain was not found to be influenced by the timing of metformin initiation or premorbid obesity in children and adolescents 5.
Metformin as a Potential Strategy for Weight Gain Prevention
- The concomitant use of metformin with antipsychotics may significantly reduce antipsychotic-induced weight gain, suggesting that metformin could be a useful strategy for preventing weight gain in patients initiating antipsychotic treatment 2, 3, 4.
- Metformin has been found to attenuate derangement of fasting glucose levels, total cholesterol, and total triglyceride levels, in addition to its effects on weight gain 4.