Dapagliflozin Versus Metformin for the Management of Antipsychotic-Induced Weight Gain: A Pragmatic Pilot Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 110
- 试验地点
- 1
- 主要终点
- Change in Body Weight
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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:
- •≥7% increase in body weight from baseline following initiation of antipsychotic treatment, or
- •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.
排除标准
- •Diabetes mellitus
- •Diagnosed patients of polycystic ovarian syndrome (PCOS)
- •Renal impairment defined as estimated glomerular filtration rate (eGFR <45 mL/min/1.73 m²)
- •Significant hepatic disease or other serious or unstable medical conditions that, in the opinion of the investigator, would make participation unsafe
- •Pregnant or breastfeeding females
- •Current use of metformin, dapagliflozin, or another sodium-glucose cotransporter 2 inhibitor.
- •Use of weight-loss medications or participation in structured weight-loss programs within the past 3 months
- •Recurrent genitourinary infections (if dapagliflozin is used)
- •Use of non-antipsychotic medications known to cause clinically significant weight gain, including but not limited to selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), mirtazapine, tricyclic antidepressants, valproate, lithium, corticosteroids, sedating antihistamines, or other medications as judged by the investigator
- •Unstable psychiatric condition or active substance use disorder that may impair the ability to adhere to study procedures, as judged by the investigator
研究组 & 干预措施
Metformin
干预措施: Metformin (Drug)
Metformin
干预措施: Common Lifestyle Program (Other)
Dapagliflozin
干预措施: Common Lifestyle Program (Other)
Dapagliflozin
干预措施: Dapagliflozin (Drug)
结局指标
主要结局
Change in Body Weight
时间窗: Baseline, Week 12, and Week 26 at the maximum tolerated dose
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.
Percent Change in Body Weight
时间窗: 26 weeks
Percentage change in body weight from baseline to week 26, measured using a calibrated digital scale. This assesses whether dapagliflozin or metformin combined with lifestyle modification reduces antipsychotic-induced weight gain compared to lifestyle modification alone.
次要结局
- Change in Body Mass Index (BMI)(Baseline, Week 12, and Week 26)
- Change in Waist Circumference(Baseline, Week 12, and Week 26)
- Change in Fasting Plasma Glucose(Baseline, Week 12, and Week 26)
- Change in Glycated Hemoglobin (HbA1c)(Baseline, Week 12, and Week 26)
- Change in Lipid Profile(Baseline, Week 12, and Week 26)
- Change in psychiatric symptom severity(Baseline, Week 12, and Week 26)
- Change in quality of life(Baseline, Week 12, and Week 26)
- Medication adherence(Week 2, Week 6, Week 12, Week 18, and Week 26)
- Adverse events and tolerability(Week 2, Week 6, Week 12, Week 18, and Week 26)
- Change in Body Mass Index (BMI)(26 weeks)
- Change in Waist Circumference(26 weeks)
- Change in Fasting Plasma Glucose(26 weeks)
- Change in Glycated Hemoglobin (HbA1c)(26 weeks)
- Change in Lipid Profile(26 weeks)
- Change in Psychiatric Symptom Severity (PANSS or BPRS)(26 weeks)
- Incidence of Adverse Events(26 weeks)
研究者
Mohammed Al Alawi MD PhD MRCPsych ARABpsych OMSBpsych
Consultant and Assistant Professor
Sultan Qaboos University