Comparative Effectiveness of Dapagliflozin, Metformin, and Lifestyle Modification for Antipsychotic-Induced Weight Gain: An Open-Label Pragmatic Trial

January 6, 2026 updated by: Mohammed Al Alawi MD PhD MRCPsych ARABpsych OMSBpsych, Sultan Qaboos University

A Three-Arm Open-Label Pragmatic Trial Comparing Dapagliflozin, Metformin, and Lifestyle Modification for Antipsychotic-Induced Weight Gain

Clinical trial:

The goal of this clinical trial is to learn if dapagliflozin can help reduce weight gain caused by antipsychotic medications in people with schizophrenia and related disorders. It will also assess the safety of dapagliflozin.

  • The main questions it aims to answer are:

    • Does dapagliflozin lower body weight compared to metformin or lifestyle changes alone?
    • Does it improve blood sugar, cholesterol, and overall health?

  • Researchers will compare three groups:

    • Dapagliflozin plus lifestyle changes
    • Metformin plus lifestyle changes
    • Lifestyle changes alone

  • Participants will:

    • Take the assigned medication daily for 26 weeks (or follow lifestyle guidance only)
    • Attend clinic visits at weeks 0, 4, 12, and 26 for measurements and blood tests
    • Receive phone calls for follow-up and side effect checks

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

The goal of this clinical trial is to learn whether a medication called dapagliflozin can help reduce weight gain caused by antipsychotic medicines. These medicines are important for treating conditions like schizophrenia, but they often lead to weight gain and other metabolic problems such as changes in blood sugar and cholesterol. This can make it harder for people to continue their treatment.

3 Researchers will compare three different approaches to see which works best to help with antipsychotic-related weight gain:

  • Metformin plus lifestyle changes (diet and exercise guidance)
  • Dapagliflozin plus lifestyle changes

  • Lifestyle changes alone

    # The main question the study aims to answer is:

  • Does dapagliflozin help people lose more weight or prevent further weight gain compared to lifestyle changes alone or metformin?

    # Other questions include:

  • How do these approaches affect blood sugar, cholesterol, and overall health?
  • How well do participants tolerate dapagliflozin compared to metformin?

  • Do these treatments improve quality of life and treatment satisfaction?

    • Study Design This is a 26-week randomized controlled trial taking place at Sultan Qaboos University Hospital in Muscat, Oman.

Participants will be randomly assigned to one of the three groups above. Neither the participants nor their doctors will be blinded, but the researchers who measure results and analyze the data will not know which group participants are in, to keep the results fair.

Who Can Take Part

People aged 16 years or older who:

  • Have a schizophrenia-spectrum disorder (as defined in DSM-5)
  • Are taking one antipsychotic medicine and have been stable for at least 3 months
  • Have gained 7% or more of their body weight since starting the medication, or have a BMI over 25 kg/m²

People cannot join if they:

  • Have diabetes, kidney, or liver disease
  • Are pregnant or breastfeeding
  • Have recently used weight-loss medications
  • Have unstable mental illness or substance use that affects study participation

What Participants Will Do All participants will receive lifestyle guidance, including diet, exercise, and behavioral support.

In addition:

  • One group will take metformin tablets twice daily
  • One group will take dapagliflozin once daily
  • One group will make lifestyle changes only

Participants will:

  • Visit the clinic at the start, and again at weeks 4, 12, and 26
  • Receive phone calls at weeks 2, 8, and 18 to check on progress and side effects
  • Have blood tests and measurements (weight, waist, glucose, cholesterol)
  • Fill out questionnaires about physical activity, mood, and quality of life

What the Study Will Measure

  • Main outcome: Change in body weight after 26 weeks
  • Other outcomes:

BMI and waist circumference Blood sugar, insulin, and cholesterol levels Percentage of people losing 5% or more of their weight Psychiatric symptom scores and quality of life Any side effects or treatment satisfaction

Why This Research Matters Many people who take antipsychotics struggle with weight gain, which can harm their health and make them stop treatment. Dapagliflozin is already used for diabetes and helps the body remove extra sugar through urine, which may also help reduce weight gain. However, no study has yet tested dapagliflozin specifically for antipsychotic-induced weight gain.

This research could identify a new, safe, and effective way to manage this problem, helping people stay healthy and continue their psychiatric treatment.

Study Type

Interventional

Enrollment (Estimated)

120

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Oman
      • Muscat, Oman
        • SQU
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age 16 years or older.
  • Diagnosis of a schizophrenia spectrum or other psychotic disorder according to DSM-5 (excluding substance/medication-induced or medical-condition-related psychoses, catatonia due to another disorder, or unspecified catatonia).
  • On stable antipsychotic monotherapy for at least 3 months before enrollment.

  • Evidence of antipsychotic-induced weight gain, defined as:

    • ≥7% increase in body weight from pre-treatment baseline, or
    • Body Mass Index (BMI) >25 kg/m² with documented antipsychotic-related weight gain.
  • Stable psychiatric symptoms, judged clinically able to give informed consent and participate in the study.

Exclusion Criteria:

  • Diabetes mellitus (type 1 or type 2).
  • Renal impairment (estimated glomerular filtration rate <45 mL/min/1.73 m²), hepatic disease, or other serious medical illness.
  • Pregnancy or breastfeeding.
  • Use of weight-loss medications or programs within the past 3 months.
  • Known hypersensitivity to metformin or dapagliflozin.
  • Unstable psychiatric condition or active substance use disorder likely to interfere with adherence or follow-up.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Arm A
Drug: Metformin (1000 mg Twice a day)
Metformin tablets starting at 500 mg twice daily and increased to 1000 mg twice daily as tolerated, taken with meals for 26 weeks.
Other: Lifestyle Modification Program
Participants receive a structured lifestyle program, including dietary counseling, physical-activity planning, and behavioral support at scheduled visits (weeks 0, 4, 12, and 26).
Experimental: Arm B
Other: Lifestyle Modification Program
Participants receive a structured lifestyle program, including dietary counseling, physical-activity planning, and behavioral support at scheduled visits (weeks 0, 4, 12, and 26).
Drug: Dapagliflozin 10 mg
Dapagliflozin 10 mg tablet taken once daily for 26 weeks. It increases glucose excretion through urine and may lower weight.
Other: Arm C
Control
Other: Lifestyle Modification Program
Participants receive a structured lifestyle program, including dietary counseling, physical-activity planning, and behavioral support at scheduled visits (weeks 0, 4, 12, and 26).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percent Change in Body Weight
Time Frame: 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.
26 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Body Mass Index (BMI)
Time Frame: 26 weeks
Change in BMI (kg/m²) from baseline to week 26 to evaluate overall body composition changes associated with each intervention.
26 weeks
Change in Waist Circumference
Time Frame: 26 weeks
Change in waist circumference (measured at the midpoint between the lowest rib and iliac crest) from baseline to week 26, assessing central fat distribution.
26 weeks
Change in Fasting Plasma Glucose
Time Frame: 26 weeks
Difference in fasting plasma glucose levels from baseline to week 26, reflecting glucose metabolism and glycemic control.
26 weeks
Change in Glycated Hemoglobin (HbA1c)
Time Frame: 26 weeks
Change in HbA1c (%) from baseline to week 26, assessing long-term glucose regulation.
26 weeks
Change in Lipid Profile
Time Frame: 26 weeks
Change in total cholesterol, LDL, HDL, and triglycerides from baseline to week 26, evaluating metabolic health and cardiovascular risk.
26 weeks
Change in Psychiatric Symptom Severity (PANSS or BPRS)
Time Frame: 26 weeks
Change in Positive and Negative Syndrome Scale (PANSS) or Brief Psychiatric Rating Scale (BPRS) total scores to evaluate the impact of interventions on psychiatric stability.
26 weeks
Incidence of Adverse Events
Time Frame: 26 weeks
Frequency and type of treatment-emergent adverse events recorded throughout the study period to evaluate safety and tolerability of each intervention.
26 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sultan Qaboos University

Investigators

  • Study Chair: Mohammed Al Alawi, MD, PhD, Sultan Qaboos University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

April 1, 2026

Primary Completion (Estimated)

November 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

January 6, 2026

First Submitted That Met QC Criteria

January 6, 2026

First Posted (Actual)

January 15, 2026

Study Record Updates

Last Update Posted (Actual)

January 15, 2026

Last Update Submitted That Met QC Criteria

January 6, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AIWG2025

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Schizophrenia Spectrum and Other Psychotic Disorders

Clinical Trials on Metformin (1000 mg Twice a day)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Austria

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe