Dapagliflozin Versus Metformin for the Management of Antipsychotic-Induced Weight Gain: A Pragmatic Pilot Randomized Controlled Trial

The goal of this clinical trial is to learn whether dapagliflozin can help manage weight gain caused by antipsychotic medications in people aged 16 years or older who are receiving antipsychotic treatment and have developed antipsychotic-induced weight gain. The main questions it aims to answer are: Can dapagliflozin reduce body weight as effectively and safely as metformin over the study period? How do dapagliflozin and metformin compare in their effects on body weight, body mass index, waist circumference, blood sugar, HbA1c, lipid profile, psychiatric symptoms, quality of life, medication adherence, and side effects? Researchers will compare dapagliflozin plus a common lifestyle program with metformin plus a common lifestyle program to see which treatment is more effective, better tolerated, and more acceptable for managing antipsychotic-induced weight gain. Participants will: Be randomly assigned to receive either dapagliflozin or metformin. Receive lifestyle advice, including dietary counselling, physical activity counselling, and behavioural support. Attend clinic visits at baseline, Week 12, and Week 26 for weight, waist circumference, blood tests, medication review, and other assessments. Receive telephone follow-up at Week 2, Week 6, and Week 18 to check medication adherence, side effects, tolerability, and lifestyle progress. Complete questionnaires and clinical assessments related to physical activity, quality of life, psychiatric symptoms, and treatment tolerability.

Inclusion criteria: * Patients aged ≥16 years * Diagnosis according to DSM-5 criteria, including: Schizophrenia spectrum and other psychotic disorders, as summarized in the DSM-5 chapter Schizophrenia Spectrum and Other Psychotic Disorders, excluding: Substance/medication-induced psychotic disorder Psychotic disorder due to another medical condition Catatonia associated with another mental disorder Catatonic disorder due to another medical condition Unspecified catatonia Bipolar and related disorders, as summarized in the DSM-5 chapter Bipolar and Related Disorders Depressive disorders, as summarized in the DSM-5 chapter Depressive Disorders Obsessive-compulsive and related disorders, as summarized in the DSM-5 chapter Obsessive-Compulsive and Related Disorders Other psychiatric conditions for which antipsychotic treatment is clinically indicated, as judged by the investigator Other conditions where antipsychotics are indicated * Receiving stable antipsychotic treatment for ≥3 months prior to enrollment * Evidence of antipsychotic-induced weight gain (AiWG), defined as: 1. ≥7% increase in body weight from baseline following initiation of antipsychotic treatment, or 2. BMI \>25 kg/m² with clinically established antipsychotic-associated weight gain * Able to understand and comply with study procedures, as judged by the investigator * Able to provide written informed consent. For participants aged 16-17 years, assent and/or guardian consent will be obtained according to local ethics committee requirements. Exclusion criteria: * Diabetes mellitus * Diagnosed patients of polycystic ovarian syndrome (PCOS) * Renal impairment defined as estimated glomerular filtration rate (eGFR \