Metformin for Antipsychotic-Induced Weight Gain in Intellectual Disability

(METIDD Trial)

Overseen By Mahavir Agarwal, MD, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: Centre for Addiction and Mental Health

Must be taking: Antipsychotics

Must not be taking: Weight-lowering agents

Disqualifiers: Pregnancy, Diabetes, Cardiovascular disease, others

Stay on Your Current Meds You can continue your current medications while participating

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if metformin, a common diabetes medication, can manage weight gain caused by antipsychotics in people with intellectual and developmental disabilities (IDD). Participants will receive either metformin or a placebo (a non-active treatment) alongside lifestyle changes, including dietary counseling and physical activity intervention, to assess its impact on weight reduction and related health issues. The trial targets adults with IDD who are on stable doses of antipsychotics and have experienced significant weight gain. It seeks to provide a new approach to addressing weight issues in this group, which often faces unique health challenges. As a Phase 4 trial, metformin is already FDA-approved and proven effective, and this research aims to understand how it benefits more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable dose of antipsychotics for at least 3 months. If you are taking weight-lowering agents or medications with significant renal impact, you may not be eligible to participate.

What is the safety track record for these treatments?

Research shows that metformin is usually easy for people to take. Studies have found that it rarely causes serious side effects. Many different groups, including those managing weight gain from antipsychotic medications, have used metformin safely. While all treatments can have side effects, metformin's history suggests that serious problems are uncommon. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about metformin for addressing antipsychotic-induced weight gain in individuals with intellectual disabilities because it offers a novel approach. Unlike typical weight management strategies, which often rely heavily on lifestyle changes alone, metformin acts by improving insulin sensitivity and altering how the body processes sugar and fat. This mechanism can potentially counteract the weight gain caused by antipsychotic medications, offering a pharmacological option that could complement lifestyle interventions. Additionally, metformin has an established safety profile from its long-standing use in managing type 2 diabetes, making it a promising candidate for this new application.

What evidence suggests that metformin might be an effective treatment for antipsychotic-induced weight gain in IDD?

Research has shown that metformin, which participants in this trial may receive, can aid weight loss for those taking antipsychotic medications. In some studies, individuals who took metformin lost weight; one study showed a decrease in body mass index (BMI) by about 0.70 kg/m². Another study found that starting metformin alongside antipsychotics reduced weight gain by about 4 kg. These findings suggest that metformin could effectively manage weight gain caused by antipsychotic medications. Since metformin is already approved for other uses, its safety is well understood. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

Adults aged 18-65 with intellectual and developmental disabilities (IDD) who are obese due to antipsychotic medications can join. They must have been on a stable dose of antipsychotics for at least 3 months, have a BMI ≥30 or ≥27 with weight-related health issues like high blood pressure. Participants should either abstain from sex or use reliable contraception during the trial.

Inclusion Criteria

I have been diagnosed with an intellectual developmental disorder.

I agree to use effective birth control or abstain from sex during the trial.

My BMI is over 30, or over 27 with a condition like high blood pressure or sleep apnea.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either metformin or placebo for 24 weeks to assess the efficacy of metformin in reducing antipsychotic-induced weight gain

24 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lifestyle Intervention
• Metformin

Trial Overview The study is testing if Metformin helps reduce weight gain caused by antipsychotic drugs in adults with IDD. It's the first study of its kind and will compare Metformin's effects against a placebo while participants also receive lifestyle advice.

How Is the Trial Designed?

Group I: Metformin (Oral) Experimental Treatment 2 Interventions

50 participants will be administered oral metformin titrated to a maximum dose of 2000mg/day for 24 weeks.

Group II: Placebo Placebo Group 2 Interventions

50 participants will be administered an identical oral placebo for 24 weeks.

Who Is Running the Clinical Trial?

Centre for Addiction and Mental Health

Lead Sponsor

Trials

388

Recruited

84,200+

Published Research Related to This Trial

Individuals with schizophrenia or schizoaffective disorders have a significantly higher prevalence of type II diabetes, prompting the need for effective treatment strategies.

The review found that diabetes education programs that include diet and exercise components, while addressing cognitive and motivational challenges, are effective in managing type II diabetes in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective lifestyle interventions to improve type II diabetes self-management for those with schizophrenia or schizoaffective disorder: a systematic review. Cimo, A., Stergiopoulos, E., Cheng, C., et al.[2021]

Behavioral weight management programs can significantly reduce weight gain in psychiatric patients taking medications, with 12 out of 17 studies showing positive results compared to usual care.

Implementing these weight management programs in outpatient settings is crucial, as psychiatric patients are at a higher risk for obesity and metabolic syndrome due to their medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy of behavioural lifestyle interventions for weight management of psychiatric patients]. Bélanger, MÈ., Provencher, MD., Shriqui, C.[2019]

Weight gain from atypical antipsychotic medications is a significant risk factor for diabetes and cardiovascular diseases, highlighting the need for effective weight management strategies in this population.

A systematic review identified 19 relevant studies, with eight selected for detailed analysis, focusing on psychoeducational, exercise, and dietary interventions to improve weight profiles in individuals with serious mental illness on these medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of weight management interventions for people with serious mental illness who receive treatment with atypical antipsychotic medications. A literature review. Lowe, T., Lubos, E.[2008]

A 12-week weight loss intervention using the DASH diet was effective for individuals on antipsychotic medications, resulting in an average weight loss from 213.3 to 206.6 pounds, while those receiving usual care did not lose weight.

The study demonstrated that it is feasible to recruit and retain participants taking antipsychotic medications for lifestyle change trials, with high satisfaction reported among participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 12-week weight reduction intervention for overweight individuals taking antipsychotic medications. Green, CA., Janoff, SL., Yarborough, BJ., et al.[2021]

In a review of 32 studies involving 1482 subjects, metformin was found to be the most effective medication for reducing weight gain associated with antipsychotic use, resulting in an average weight loss of 2.94 kg compared to placebo.

While five out of fifteen medications tested showed some efficacy in reducing weight gain, none were able to completely reverse the weight gain caused by antipsychotics, highlighting the need for better treatment options with minimal metabolic side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. Maayan, L., Vakhrusheva, J., Correll, CU.[2022]

A systematic review of 13 trials, including eight randomized, double-blind, placebo-controlled studies, found that metformin is well tolerated but has limited evidence for effectively reducing weight gain caused by atypical antipsychotic medications.

The current evidence is weak, indicating a need for more robust studies with larger sample sizes and longer durations to better assess metformin's potential in managing weight gain in patients taking atypical antipsychotics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of metformin to limit weight-gain with atypical antipsychotics. Lee, YJ., Jeong, JH.[2018]

Behavioral weight loss interventions, when started at the beginning of atypical antipsychotic treatment, can significantly reduce weight gain associated with these medications, while interventions started later can lead to weight loss.

Across various studies, participants experienced average weight losses of 2.63 kg for 12- to 16-week interventions, 4.24 kg for 6-month interventions, and 3.05 kg for 12- to 18-month interventions, along with improvements in insulin regulation and HbA1c levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of behavioural interventions in managing atypical antipsychotic weight gain. Gabriele, JM., Dubbert, PM., Reeves, RR.[2018]

Most antipsychotics lead to weight gain, with olanzapine and clozapine being the most likely to cause significant increases, particularly in children who are especially vulnerable.

While switching to antipsychotics with lower weight gain potential is an option, it may risk relapse; nonpharmacologic strategies like diet and exercise show modest effectiveness, and metformin has the best evidence as an add-on for weight loss, though routine use of such medications is not strongly supported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Dayabandara, M., Hanwella, R., Ratnatunga, S., et al.[2022]

In a case series of 11 adults with intellectual and developmental disabilities (IDD) on antipsychotics, metformin treatment resulted in an average weight loss of 11.1 kg, with over 50% of patients achieving clinically significant weight loss of more than 7%.

Metformin also led to improvements in metabolic markers such as fasting glucose and cholesterol levels, suggesting it may be a safe and effective option for managing antipsychotic-induced metabolic issues in individuals with IDD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Addressing Metabolic Comorbidity in Individuals With Intellectual and Developmental Disability on Antipsychotics: A Clinical Case Series. Stogios, N., Hahn, MK., Lunsky, Y., et al.[2023]

People with schizophrenia often experience obesity and related health issues, such as type 2 diabetes and cardiovascular disease, largely due to weight gain from antipsychotic medications.

While short-term behavior therapy programs have shown promise for weight control in schizophrenia, there is a need for long-term studies and the adaptation of lifestyle change programs to help manage weight effectively in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight gain from novel antipsychotic drugs: need for action. Green, AI., Patel, JK., Goisman, RM., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05744479

Metformin for Antipsychotic-induced Weight Gain in Adults ... This is the the first RCT (randomized control trial) to examine the efficacy of metformin in overweight or obese adults with IDD who have experienced ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8788031/

Metformin in the management of antipsychotic-induced ... Those assigned to both metformin groups reported significant reductions in BMI, with a mean decrease of 0.70 kg/m2 (p=0.021) and 0.50 kg/m2 (p= ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05744479/metformin-for-antipsychotic-induced-weight-gain-in-adults-with-intellectual-disability

Metformin for Antipsychotic-induced Weight Gain in Adults ... This is the the first RCT (randomized control trial) to examine the efficacy of metformin in overweight or obese adults with IDD who have ...

4. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2024.1491417/full

Metformin in the management of antipsychotic-induced ... Clinically significant weight gain (≥7% increase in weight) has been linked to almost all antipsychotics (2). Adjunctive metformin treatment has been ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12414565/

Metformin for the Prevention of Antipsychotic-Induced ... Co-commencement with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg (95% CI −5.78 kg to −2.28 kg) compared to controls.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10019321/

Metformin for the treatment of antipsychotic-induced ... The patient gained more than 23 kg (50 lb) in the 6 months after starting antipsychotic treatment, positioning her in the class I level of ...

7. academic.oup.com academic.oup.com/schizophreniabulletin/article/51/5/1193/7919241

Metformin for the Prevention of Antipsychotic-Induced Weight ... Co-commencement with antipsychotic medicines can reduce the extent of weight gain by 4.03 kg (95% CI −5.78 kg to −2.28 kg) compared to controls.