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.
This is an open-label, pragmatic, parallel-group pilot randomized controlled trial comparing dapagliflozin with metformin for the management of antipsychotic-induced weight gain. The study will be conducted at the Department of Behavioral Medicine, Sultan Qaboos University Hospital, University Medical City, Muscat, Oman. Antipsychotic-induced weight gain is a common and clinically important adverse effect of antipsychotic treatment. It may contribute to reduced treatment adherence, poorer quality of life, and increased cardiometabolic risk. Metformin is commonly used to manage antipsychotic-associated weight gain, but its use may be limited by gastrointestinal adverse effects, dose titration, and pill burden. Dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, has demonstrated weight-reducing and metabolic benefits in other clinical populations, but its role in antipsychotic-induced weight gain remains insufficiently studied. Participants will be randomized in a 1:1 ratio to receive either dapagliflozin plus a common lifestyle program or metformin plus a common lifestyle program. The trial will use a pragmatic PROBE-style design, with open-label treatment allocation and blinded outcome assessment and statistical analysis where feasible. Randomization will use a computer-generated sequence with allocation concealment. The study is designed as a pilot trial to assess feasibility, tolerability, adherence, safety, and preliminary estimates of treatment effect to inform a future definitive trial. Standardized procedures will be used for participant follow-up, medication review, safety monitoring, and data collection. Adverse events and treatment tolerability will be monitored throughout the study, and serious adverse events will be reported according to institutional and ethics committee procedures. Data will be collected by trained study personnel and entered into an electronic database with procedures to support completeness and accuracy. Analyses will be primarily descriptive and exploratory, consistent with the pilot nature of the trial, and will be used to refine assumptions for a future larger randomized controlled trial.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
110
Dapagliflozin will be administered orally at a dose of 10 mg once daily. Treatment will continue for 26 weeks. Participants will be monitored for adherence, tolerability, and adverse events, including genitourinary symptoms, dehydration, sick-day events, and symptoms suggestive of ketoacidosis.
Metformin will be administered orally. Participants will start with 500 mg twice daily, taken with meals, and will be titrated to 1000 mg twice daily by the second week as tolerated. Slower titration may be used if gastrointestinal side effects occur. Treatment will continue for the study period, with the primary endpoint assessed after 26 weeks at the maximum tolerated dose.
All participants will receive a standardized common lifestyle program. This will include dietary counselling, physical activity counselling, and behavioural support delivered at baseline and reinforced during scheduled in-person visits and telephone follow-up. Physical activity will be assessed using the International Physical Activity Questionnaire.
SQU
Muscat, Oman
Change in Body Weight
Change in body weight from baseline to the primary endpoint. Body weight will be measured using standardized procedures and compared between the dapagliflozin plus common lifestyle program arm and the metformin plus common lifestyle program arm.
Time frame: Baseline, Week 12, and Week 26 at the maximum tolerated dose
Change in Body Mass Index (BMI)
Change in BMI (kg/m²) from baseline to week 26 to evaluate overall body composition changes associated with each intervention.
Time frame: Baseline, Week 12, and Week 26
Change in Waist Circumference
Change in waist circumference (measured at the midpoint between the lowest rib and iliac crest) from baseline to week 26, assessing central fat distribution.
Time frame: Baseline, Week 12, and Week 26
Change in Fasting Plasma Glucose
Difference in fasting plasma glucose levels from baseline to week 26, reflecting glucose metabolism and glycemic control.
Time frame: Baseline, Week 12, and Week 26
Change in Glycated Hemoglobin (HbA1c)
Change in HbA1c (%) from baseline to week 26, assessing long-term glucose regulation.
Time frame: Baseline, Week 12, and Week 26
Change in Lipid Profile
Change in total cholesterol, LDL, HDL, and triglycerides from baseline to week 26, evaluating metabolic health and cardiovascular risk.
Time frame: Baseline, Week 12, and Week 26
Change in psychiatric symptom severity
* Psychotic symptom severity will be assessed using the Brief Psychiatric Rating Scale, an 18-item clinician-rated scale. Total scores range from 18 to 126, with higher scores indicating greater psychotic symptom severity. * Depressive symptom severity will be assessed using the 17-item Hamilton Depression Rating Scale. Total scores range from 0 to 52, with higher scores indicating greater depressive symptom severity. * Manic symptom severity will be assessed using the Young Mania Rating Scale, an 11-item clinician-rated scale. Total scores range from 0 to 60, with higher scores indicating greater manic symptom severity. * Obsessive-compulsive symptom severity will be assessed using the Yale-Brown Obsessive Compulsive Scale. Total scores range from 0 to 40, with higher scores indicating greater obsessive-compulsive symptom severity.
Time frame: Baseline, Week 12, and Week 26
Change in quality of life
Change in health-related quality of life assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L).
Time frame: Baseline, Week 12, and Week 26
Medication adherence
Assessment of participant adherence to the assigned intervention during scheduled visits and telephone follow-up.
Time frame: Week 2, Week 6, Week 12, Week 18, and Week 26
Adverse events and tolerability
Frequency, severity, duration, action taken, and outcome of adverse events and tolerability issues reported during the study period.
Time frame: Week 2, Week 6, Week 12, Week 18, and Week 26
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