Metformin for the Prevention of Antipsychotic-Induced Weight Gain: The Optimal Strategy

See letter by Mulsant et al and article by Daggolu and Chen

To the Editor: I read Mulsant and colleagues’ letter¹ commenting on Daggolu and Chen’s article,² which discussed improved adherence to, and potentially effectiveness of, second-generation antipsychotics (SGAs) coprescribed with metformin. They called attention to an important safety consideration: the association between metformin and vitamin B₁₂ deficiency based on the evidence that the prevalence of B₁₂ deficiency has been reported in 6%–50% of patients with diabetes receiving long-term treatment with metformin.

Indeed, the data concerning the prevalence of B₁₂ deficiency in patients coprescribed antipsychotics and metformin have not been well-studied. However, there is an article researching the influence of SGAs on one-carbon metabolism markers, including vitamin B₁₂, in schizophrenia.³ The authors found that SGA, including olanzapine and risperidone, may decrease vitamin B₁₂ level after 12 weeks of SGA treatment of first-episode schizophrenia patients. This information may provide readers with a fuller grasp of the relevant issue.

In conclusion, I agree with Mulsant and colleagues’ suggestion that clinicians who decide to coprescribe antipsychotics and metformin need to consider the associated risk of B₁₂ deficiency and its neuropsychiatric sequelae. Based on the relevant expert consensus,⁴ prophylactic oral supplementation should be considered in clinical practice to mitigate this risk. Furthermore, I encourage clinicians to use a shared decision-making approach based on individual risk factors and preferences, with the help of the latest guidelines,⁵ including explaining the benefits and drawbacks of concurrent metformin with patients, when initiating antipsychotics.

Article Information

Published Online: April 6, 2026. https://doi.org/10.4088/JCP.25lr16260b
© 2026 Physicians Postgraduate Press, Inc.
J Clin Psychiatry 2026;87(2):25lr16260b
To Cite: Huang CLC. Metformin for the prevention of antipsychotic-induced weight gain: the optimal strategy. J Clin Psychiatry. 2026;87(2):25lr16260b.
Author Affiliations: Department of Psychiatry, Chi Mei Medical Center, Tainan, Taiwan; and Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung, Taiwan.
Corresponding Author: Charles Lung-Cheng Huang, MD, PhD, Department of Psychiatry, Chi Mei Medical Center, 901, Chung Hwa Rd Yung Kang, Tainan, 710, Taiwan ([email protected]).
Financial Disclosure: None.
Funding/Support: None.
ORCID: Charles Lung-Cheng Huang: https://orcid.org/0000-0002-7898-1641