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Metformin for Managing Weight Gain in Patients Taking Antipsychotic Medications

By Dr. Eappen

There is no sugar-coating the fact that antipsychotic medications can cause side effects. Antipsychotics (including clozapine, olanzapine, risperidone, or sulpiride) are prescribed to treat bipolar disorder, major depression, anxiety, delirium, and all psychotic disorders.

While these medications can greatly improve the quality of life for people with debilitating symptoms, it is always important to weigh the benefits against the risks for each individual patient.

One common side effect of taking an antipsychotic is increased risk of weight gain, as well as increased risk of metabolic syndrome.  Metabolic syndrome is an accumulation of several disorders, which together raise the risk of developing heart disease, diabetes, and stroke.  The metabolic syndrome is diagnosed if a patient has any 3 of the following:

  • High blood sugar levels (glucose of 100mg/dL or greater)
  • Low levels of HDL (“good”) cholesterol in the blood (less than 40 mg/dL in men, less than 50mg/dL in women)
  • High levels of triglycerides (a type of fat) in the blood (150 mg/DL or higher)
  • Large waist circumference (more than 40 inches in men, more than 35 inches in women)
  • High blood pressure (130/85 or higher)

While metabolic syndrome and weight gain are serious health concerns, these problems also increase risk of other serious medical diseases such as heart disease and stroke.  In one study, the risk of coronary artery disease and stroke was found to be tripled among subjects with metabolic syndrome as compared with those who did not have metabolic syndrome.  For this reason, clinicians and patients need to work together to manage this challenge.

Various lifestyle interventions (e.g., dietary counseling, exercise programs, and cognitive and behavioral strategies) can counteract antipsychotic-induced weight gain and metabolic syndrome risk, but in cases where these interventions are not being done or are minimally effective, adding on medication specifically to target this works best. One medication that has a high evidence base for reducing risk of weight gain and metabolic syndrome is metformin. Let’s look at the evidence base for prescribing metformin for the purpose of weight management in patients taking antipsychotics.

Understanding How Metformin Works

Many of my patients are familiar with metformin as a drug approved for treatment of type 2 diabetes. Metformin lowers your blood sugar levels by improving how your body processes insulin. It’s typically prescribed for those with diabetes for whom diet and exercise alone have not been enough to control blood sugar levels.

One reason that many of my patients feel good about taking metformin is that it has a long history. In 1918, a scientist discovered that guanidine (one of metformin’s main ingredients) could lower blood sugar. Metformin was then developed and approved to treat diabetes in Europe in the 1950s. The FDA first approved it for use in the US in 1995. Since then, metformin has become the most widely prescribed medication for treatment of type 2 diabetes.

Metformin has also been studied for treatment of weight gain in the absence of diabetes in children who are taking antipsychotics. It has been shown to significantly reduce body mass index (BMI), with few to no adverse effects, in a randomized clinical trial of 39 children aged 10 to 17 who were taking antipsychotic medications. In adults, the use of metformin can stop or reverse weight gain associated with taking antipsychotics.

Despite these positive findings, some patients who experience weight gain prefer to try lifestyle interventions first. This may be because these patients are reluctant to take what they see as a “diabetes medicine” when they themselves might not have been diagnosed with diabetes, or because they are worried about taking too many pills. However, most of my patients dealing with weight gain come around to the idea of taking metformin if lifestyle interventions fail to work for them.

healthy habits like healthy eating are essential for weight reduction while on an atypical antipsychotic

While lifestyle changes have been found to reduce obesity or prevent weight gain induced by antipsychotic medications, metformin has also been found to do the same.  Until 2008, there were no double-blind, placebo controlled trials that compared lifestyle intervention and metformin alone or in combination for weight gain induced by antipsychotics, until this study was published.

Lifestyle Intervention and Metformin for Treatment of Antipsychotic-Induced Weight Gain: The Study

Because weight gain and metabolic syndrome are common side effects of taking antipsychotic medications, doctors and their patients have been in serious need of a solution to this problem. Recognizing this need, a group of scientists working in China collaborated with psychiatrists at the University of California, San Diego to conduct this study

The Hypothesis

Researchers set out to test the efficacy of lifestyle changes and metformin alone and in combination for the treatment of antipsychotic-induced weight gain. Prior to this study, no double-blind, placebo-controlled studies had directly compared lifestyle intervention and metformin alone or in combination for weight gain associated with antipsychotic medications.

Methods Used

To be eligible to participate, patients were aged 18 to 45 who had been diagnosed with schizophrenia, which is a type of psychotic disorder. Although all participants were diagnosed with schizophrenia, the study results have relevance for any patient taking antipsychotics. 

Other enrollment criteria included that participants had gained more than 10% of their body weight within the first year of treatment with an antipsychotic (i.e., clozapine, olanzapine, risperidone, or sulpiride) and had been taking only one antipsychotic medication, whose dosage had been relatively stable.

woman reading a weight loss book on lifestyle modifications, physical activity, gut bacteria, energy intake, lipid metabolism and amp activated protein kinase

All participants were under the care of a caregiver who monitored their food intake, exercise activity, and medication each day during the trial. 128 adult participants were recruited from the schizophrenia outpatient clinic of the Mental Health Institute of the Second Xiangya Hospital, Central South University, China, between October 2004 and December 2006.

During the trial, patients continued their antipsychotic medication and were randomly assigned to 12 weeks of placebo, 750 milligrams per day of metformin alone, 750 milligrams per day of metformin and lifestyle intervention, or lifestyle intervention only.

Results

All 128 patients maintained relatively stable psychiatric improvement. The lifestyle-plus-metformin group had mean decreases in body mass index (BMI) of 1.8, insulin resistance index of 3.6, and waist circumference of 2.0 centimeters. The metformin-alone group had mean decreases in BMI of 1.2, insulin resistance index of 3.5, and waist circumference of 1.3 centimeters. The lifestyle-plus-placebo group had mean decreases in BMI of 0.5 and insulin resistance index of 1.0. However, the placebo group had mean increases in BMI of 1.2, insulin resistance index of 0.4, and waist circumference of 2.2 centimeters. 

The bottomline: The lifestyle-plus-metformin treatment was significantly superior to metformin alone and to lifestyle plus placebo for weight, BMI, and waist circumference reduction. Also, metformin alone was more effective in weight loss and improving insulin sensitivity than lifestyle intervention alone.

Conclusion

No one wants to gain weight, but everyone wants to be mentally healthy. When the medication you’re prescribed improves your mental health, but causes you to gain weight, it can feel as if you’re trapped between a rock and a hard place – feeling good mentally vs. feeling good physically. Fortunately, metformin can be a way out for many patients who feel this way.

If you’re concerned about weight gain associated with antipsychotic medication, contact us for a consultation. Lifestyle changes can help, but if you’re not seeing the results you want, remember that you have other options.

About the Author

Seth Eappen, MD, is a board-certified adult, child and adolescent psychiatrist. Dr. Eappen completed medical school at the University of Illinois at Chicago and a residency at the University of Michigan, Ann Arbor. He completed his child psychiatry fellowship at MUSC in Charleston, SC, where he served as chief fellow. He is the founder of the Eappen Clinic, a private outpatient mental health practice with locations in Chicago and Oak Brook, IL.