Metformin Emerges as a Promising Option to Manage Weight Gain in Young People Taking Bipolar Medications

A major new study has brought encouraging news for young people dealing with bipolar disorder and the difficult side effects that can come with treatment. Researchers have found that metformin, a widely used medication for Type 2 diabetes, can meaningfully reduce or prevent weight gain caused by second-generation antipsychotics (SGAs) in children and teens. This finding is important because SGAs—though often highly effective for treating bipolar disorder—can lead to elevated appetite, rapid weight gain, and long-term health risks. These side effects frequently cause patients to stop taking their medications, which can destabilize mental health.

This newly published study, called MOBILITY, is the largest and longest trial ever conducted to test metformin for this purpose in young people. The results support adopting metformin as a new standard of care for overweight or obese youth who are being treated with SGAs.

What Exactly Was Studied?

The trial, funded and led by researchers at the University of Cincinnati and Cincinnati Children’s Hospital, enrolled 1,565 young participants aged 8–19 years. All of them had a bipolar spectrum disorder and were currently taking an SGA—medications such as quetiapine, risperidone, aripiprazole, and others.

Every participant received a brief healthy lifestyle intervention, which included guidance on nutrition, physical activity, and sustainable habits. After that, half of the participants were randomly assigned to also take metformin, while the other half continued with only the lifestyle guidance.

The study used a pragmatic design, meaning it focused on real-world clinics instead of only academic research settings. This included many community mental health clinics that had never participated in clinical research. This design makes the findings much more useful in practical day-to-day psychiatric care, because it reflects how patients are actually treated outside of research environments.

Key Results at 6 Months and 24 Months

When researchers checked in at 6 months and again at 24 months, a consistent pattern emerged:

• Youth who received metformin + lifestyle intervention showed greater decreases in BMI z-scores than youth who only received lifestyle support.
• The difference was modest but clinically meaningful, according to the research team.
• Metformin was well tolerated, with no major adverse events reported over the course of the study.
• The most common side effects were gastrointestinal issues, such as stomach discomfort or nausea, but these were usually manageable through simple strategies like taking the medication with food or switching to an extended-release version.

Because even small reductions in weight gain can significantly reduce long-term health risks, the researchers concluded that the benefits outweigh the risks for most patients.

Why This Matters for Mental Health Treatment

SGAs are powerful mood-stabilizing medications, but they come with challenges. They can increase appetite and make it easier to gain weight quickly. In youth, this issue is especially serious because:

• Early weight gain increases the chance of developing insulin resistance, high cholesterol, high blood pressure, and type 2 diabetes later in life.
• These risks can stay with a person for decades.
• Weight changes often cause young patients to stop taking their psychiatric medications, leading to relapses or worsening symptoms.

By helping manage this side effect, metformin could make it easier for patients to stay on their prescribed treatments while protecting their physical health.

Growing Support in Medical Guidelines

Coinciding with the publication of the trial’s results, several national and international medical guidelines have started recommending metformin as a preventive option for patients—both youth and adults—who are at risk of gaining weight from SGAs.

According to the lead investigators, clinicians should consider starting metformin at the same time an SGA is prescribed for a young patient who is already overweight or obese. This proactive approach may help prevent rapid weight gain early on, instead of trying to treat it years later.

How Metformin Compares to Newer Weight-Loss Drugs

Over the past few years, GLP-1 agonists like Ozempic and Wegovy have become extremely popular for weight management. However:

• They have not been studied enough for long-term safety in young people with mental health disorders.
• Some concerns exist about their impact on appetite, mood, and psychiatric stability.
• They are far more expensive and often inaccessible for many families.
• Metformin, on the other hand, has decades of safety data, is affordable, and is widely available.

This makes metformin a practical and realistic option for most clinics and families.

Conducting the Study During the Pandemic

A remarkable aspect of the MOBILITY trial is that much of it took place during the COVID-19 pandemic, when clinical research worldwide faced disruptions. Despite this challenge, the trial remained successful due to:

• Strong collaboration between multiple major health institutions.
• Support from dedicated clinicians (“champions”) at every trial site.
• Involvement of patients and caregivers in the trial planning and execution.

The study was carried out across a wide network of community and academic mental-health clinics throughout the United States, making the findings broadly relevant.

Additional Background: How Metformin Works

Though metformin is best known as a diabetes medication, its effects on weight regulation are well understood. Metformin can:

• Improve how the body uses insulin.
• Reduce excess sugar produced by the liver.
• Help lessen hunger or appetite spikes.
• Support better metabolic stability.

Because SGAs can disrupt metabolism and appetite, these actions make metformin a good fit for counteracting the physical side effects of psychiatric treatment.

Additional Background: Why SGAs Cause Weight Gain

Second-generation antipsychotics affect several neurotransmitter systems, including:

• Serotonin
• Dopamine
• Histamine

These changes can lead to:

• Increased appetite
• Slower metabolism
• Altered glucose processing
• Greater fat storage

This combination can produce surprisingly rapid weight gain—sometimes within just a few weeks of starting treatment. Young people are especially vulnerable because their bodies are still developing.

What This Study Means Moving Forward

With more than 1,500 participants and two full years of follow-up, the MOBILITY trial adds a significant amount of solid evidence to support a simple message:

Metformin may help protect the physical health of young people who need SGAs to manage bipolar disorder.

The researchers hope that these findings will encourage more clinicians to include metformin as part of a comprehensive treatment plan when appropriate. For patients and families, this could mean better mental-health outcomes, fewer long-term health risks, and improved quality of life.

Research Paper

Metformin for overweight and obese children and adolescents with bipolar spectrum and related mood disorders treated with second-generation antipsychotics: a randomised, pragmatic trial
https://doi.org/10.1016/s2215-0366(25)00273-1