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

Sultan Qaboos University

Status and phase: Begins enrollment in 1 month; Phase 4

Conditions: Schizophrenia Spectrum and Other Psychotic Disorders; Antipsychotic-induced Weight Gain; Antipsychotic-induced Weight Gain (AIWG)

Treatments: Drug: Metformin (1000 mg Twice a day); Drug: Dapagliflozin 10 mg; Other: Lifestyle Modification Program

Study type: Interventional

Funder types: Other

Identifiers

NCT07342764

AIWG2025

Details and patient eligibility

About

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

Full 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.

Enrollment: 120 estimated patients

Sex: All

Ages: 16 to 60 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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120 participants in 3 patient groups

Arm A

Active Comparator group

Treatment:

Other: Lifestyle Modification Program

Drug: Metformin (1000 mg Twice a day)

Arm B

Experimental group

Treatment:

Other: Lifestyle Modification Program

Drug: Dapagliflozin 10 mg

Arm C

Other group

Description:

Control

Treatment:

Other: Lifestyle Modification Program