Metformin for Antipsychotic-Induced Weight Gain in Intellectual Disability

(METIDD Trial)

Overseen By Mahavir Agarwal, MD, PhD

Age: 18+

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

Trial Summary

What is the purpose of this trial?

People with IDD (intellectual and developmental disability) have very high rates of obesity and die prematurely from cardiometabolic disease. While antipsychotics contribute to this problem, their use is necessary and appropriate in a significant subgroup of individuals with IDD. Exercise and diet interventions have limitations and may not be sufficient, requiring effective adjunctive pharmacological approaches to target obesity and related comorbidities in IDD. However, persons with IDD treated with antipsychotics are systematically excluded from clinical trials hindering development of evidence to help guide safe and effective treatment of these comorbidities. Moreover, evidence from other disorders cannot be extrapolated to IDD given inherent biological differences between disorders. This trial will address the identified gaps, which extend beyond cardiovascular morbidity and negatively impact psychosocial outcomes, in a hugely underserviced population.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 antipsychotic-induced weight gain. By generating efficacy data for a very accessible and scalable intervention, allows for guideline and implementation strategies to address a recalcitrant health problem.

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 data supports the effectiveness of the drug Metformin for antipsychotic-induced weight gain in individuals with intellectual disability?

Research shows that Metformin can lead to weight loss in people experiencing weight gain from antipsychotic medications, with studies indicating an average weight loss of about 2.94 kg. Additionally, behavioral interventions like lifestyle changes and dietary counseling have been effective in managing weight gain associated with antipsychotic use. ^{1 2 3 4 5}

Is Metformin safe for managing weight gain in people taking antipsychotics?

Metformin has been studied as an add-on medication to help with weight loss in people taking antipsychotics, and it has the best evidence for safety and effectiveness among various options. However, the burden of side effects should be considered when prescribing it for weight reduction. ^{1 3 6 7 8}

How does the drug metformin differ from other treatments for antipsychotic-induced weight gain in individuals with intellectual disability?

Metformin is unique because it is primarily a diabetes medication that has shown effectiveness in reducing weight gain caused by antipsychotic medications, which is a common issue for individuals with intellectual disabilities. Unlike other treatments, metformin has the best evidence for weight loss in this context, although its effects are modest and it does not completely reverse the weight gain. ^{4 5 8 9 10}

Eligibility Criteria

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 am between 18 and 65 years old.

I have been diagnosed with an intellectual developmental disorder.

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

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2008]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy of behavioural interventions in managing atypical antipsychotic weight gain. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Weight gain from novel antipsychotic drugs: need for action. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Addressing Metabolic Comorbidity in Individuals With Intellectual and Developmental Disability on Antipsychotics: A Clinical Case Series. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Effectiveness of medications used to attenuate antipsychotic-related weight gain and metabolic abnormalities: a systematic review and meta-analysis. [2022]

6. Canada pubmed.ncbi.nlm.nih.gov

[Efficacy of behavioural lifestyle interventions for weight management of psychiatric patients]. [2019]

7. England 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. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

A 12-week weight reduction intervention for overweight individuals taking antipsychotic medications. [2021]

10. England pubmed.ncbi.nlm.nih.gov

A systematic review of metformin to limit weight-gain with atypical antipsychotics. [2018]