Metformin for Antipsychotic-Induced Weight Gain in People with Severe Mental Illness
Antipsychotic induced weight gain in people with severe mental illness
Intervention: Film coated tablets of metformin XR, starting at 500 mg daily and titrating up to 2000 mg daily over a 6-week period, orally for a total of 26 weeks. Control: Placebo - identical-looking tablets titrated in the same way as the intervention over a period of three weeks and then continued for 26 weeks duration. Eligible participants will be randomised to metformin or placebo in a 1:1 ratio using a computer-generated randomisation table provided by an independent, non-blinded statistician. The randomisation table will be provided to an independent pharmacy team at each site. This pharmacy team, as well as the non-blinded statistician, will be the only services with the ability to unblind patients. Participants will be provided with a 24 hours contact number in case there is an emergent situation where it is crucial that medical staff know whether they are receiving metformin or placebo.
Current key inclusion criteria as of 13/08/2026: 1. Clinical diagnosis of SMI (i.e. schizophrenia, schizoaffective disorder, bipolar affective disorder, psychosis, severe depression with psychosis) 2. On antipsychotic medication 3. Able to, and willing to provide informed consent 4.≥18 years of age 5. BMI ≥18.5 kg/m² _____ Previous key inclusion criteria as of 17/10/2025: 1. Clinical diagnosis of SMI (i.e. schizophrenia, schizoaffective disorder, bipolar affective disorder, psychosis, severe depression with psychosis) 2. Antipsychotic naive 3. Able to, and willing to provide informed consent 4.=/ >18 years of age 5. BMI=/ > 18.5 kg/m² 6. Taking antipsychotic medication for < 28 days _____ Previous key inclusion criteria: 1. Clinical diagnosis of SMI (i.e. schizophrenia, schizoaffective disorder, bipolar affective disorder, psychosis, severe depression with psychosis) 2. Antipsychotic naive 3. Able to, and willing to provide informed consent 4. >18 years of age 5. BMI > 18.5 kg/m² 6. Taking antipsychotic medication for < 28 days
1. BMI < 18.5 kg/m² 2. Known allergies or contra-indications to metformin or any part of the formulation of the placebo or investigational product 3. Diagnosis of type 1 or type 2 diabetes, or already taking metformin 4. Found to have HbA1c within diabetes range from blood tests 5. Prior diagnosis of a condition which is directly associated with obesity (self-reported) 6. Obesity induced by other endocrine disorder 7. Chronic kidney disease (eGFR < 30 mL/min) 8. Concomitant disease or condition (neurodegenerative disease, cognitive impairment) that investigators consider makes the patient unsuitable for trial participation 9. Taking weight-lowering therapy including: pramlintide, sibutramine, orlistat, zonisamide, topiramate or phentermine (or part of a clinical trial of such treatments) 10. Previous surgical treatment of obesity 11. Women who are pregnant or breast-feeding, or of childbearing age and not using contraceptives 12. Unable to provide informed consent, or lacking capacity