Metformin for Outpatients with Psychosis

Summary and Comment |
July 15, 2013

Metformin for Outpatients with Psychosis

  1. Joel Yager, MD

Metformin was modestly helpful in reducing weight and triglycerides in typical outpatients with schizophrenia and schizoaffective psychosis.

  1. Joel Yager, MD

Obesity and cardiovascular disease risks are elevated in patients with schizophrenia and contribute significantly to premature death in these patients. Previous studies of metformin in schizophrenia patients have involved highly selected populations and have yielded inconsistent results. In this first-ever, randomized, controlled trial of metformin added to ongoing psychiatric medication, 148 typical outpatients with schizophrenia or schizoaffective disorder (mean age, 43) were randomized to 16 weeks of metformin (increased as tolerated to 1000 mg twice daily) or placebo.

All patients were taking one or two antipsychotics and received diet and exercise counseling. Patients with diabetes mellitus were excluded. At entry, participants had a mean weight of 101.9 kg (mean body-mass index, 34.6) and averaged marginally high triglyceride levels (150.3 mg/dL). Mean total, low-density and high-density lipoprotein cholesterol, and hemoglobin A1C levels were within normal ranges.

Completers included 77% of metformin patients and 82% of placebo patients. Metformin was associated with greater weight loss (3.0 vs. 1.0 kg with placebo; reduction in weight, 2.8% vs. 1.0%) and improvement in triglyceride levels (–7.0 vs. +13.2 mg/dL). Adherence to metformin was excellent, with no major related adverse events.


This study did not standardize diet or extent of exercise. Still, in this population, add-on metformin was associated with modestly improved weight and triglyceride levels. The differences in triglyceride levels seem particularly noteworthy. Other research suggests that patients taking metformin for longer periods are likely to experience even greater weight loss and metabolic improvement. In this study, the differences in triglyceride levels seem particularly noteworthy. How much these modest changes might improve health outcomes in the long run remains to be seen, but with few other options and metformin's few adverse effects, psychiatric practitioners should become comfortable in prescribing this medication.

Editor Disclosures at Time of Publication

  • Disclosures for Joel Yager, MD at time of publication Editorial boards Bulletin of the Menninger Clinic; Eating Disorders: Journal of Treatment and Research; Eating Disorders Review (Editor-in-Chief); Harvard Review of Psychiatry; International Journal of Eating Disorders; UpToDate Leadership positions in professional societies American Psychiatric Association (Chair, Steering Committee and Executive Committee on Practice Guidelines; Co-Chair, DSM5 Clinical and Public Health Committee; Chair, Council on Research and Quality Care)


Reader Comments (5)


Thank you for sharing the info on Metformin. Very helpful. For me, I lost the most weight when I started making diet changes, instead of taking pills. Adding a green smoothie to my diet has been great and gives me a ton of energy. If you mix up your smoothie blend it is easy to keep going and even do a short green smoothie detox. You will lose weight and feel better than taking Metformin.


Bruce Relyea MD Other, Internal Medicine, Retired

A book entitled "Could It Be B-12? An Epidemic of Misdiagnoses" by Sally M Pacholok, R.N., B.S.N. and Jeffrey J. Stuart, D.O. makes the point that metformin interferes with the absorption of Vitamin B-12. The following article in the Southern Medical Journal entitled

Metformin-induced Vitamin B12 Deficiency Presenting as a Peripheral Neuropathy
David S.H. Bell, MD
South Med J. 2010;103(3):265-267.
So, Vitamin B-12 levels may have dropped, leading to peripheral neutopathy

Suzanne Markov Other, Other, Retired

Has Metformin been tried in treating patients diagnosed with Bipolar Disorder I ? If it were to be tried, could it be expected that it would have the same beneficial results it appears to have in treating their
frequently accompanying obesity and cardiovascular risks? Why do these trials never seem to include Bipolar Disorder?

Victor Olisah Physician, Psychiatry, Ahmadu Bello University Teaching Hospital, Zaria, Kaduna State, Nigeria

The study did not indicate what happened to the blood sugar levels of the participants. I am particularly concerned about non diabetic Schizophrenic patients receiving 1000mg of Metformin twice daily.

Barbara McGovern Other, Diasables ICU/Trauma RN

This article and those of this nature, are of great interest to me, personally. Thank you.

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