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

NCT07342764 | Not Yet Recruiting Phase 4

• 1 other identifier: AIWG2025
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Antipsychotic-induced Weight Gain (AIWG); Antipsychotic-induced Weight Gain

Keywords

Dapagliflozin; Metformin; Antipsychotic-induced weight gain; Psychotic disorders; Randomized controlled trial; Weight management; Metabolic side effects; Lifestyle intervention; SGLT2 inhibitor

Outcome Measures

Primary Outcomes (1)

• 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.

  Baseline, Week 12, and Week 26 at the maximum tolerated dose

Secondary Outcomes (9)

• 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

Other Outcomes (1)

• Physical activity assessed using the International Physical Activity Questionnaire-Short Form (IPAQ-SF)

  Baseline, Week 12, and Week 26

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Drug: Metformin; Other: Common Lifestyle Program

Dapagliflozin

EXPERIMENTAL

Drug: Dapagliflozin; Other: Common Lifestyle Program

Interventions

Dapagliflozin DRUG

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.

Dapagliflozin

Metformin DRUG

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.

Metformin

Common Lifestyle Program OTHER

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.

Dapagliflozin; Metformin

Eligibility Criteria

• Age: 16 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Sultan Qaboos University: lead

Study Sites (1)

SQU

Muscat, Oman

Location

Related Publications (9)

• Ferreira-Hermosillo A, Molina-Ayala MA, Molina-Guerrero D, Garrido-Mendoza AP, Ramirez-Renteria C, Mendoza-Zubieta V, Espinosa E, Mercado M. Efficacy of the treatment with dapagliflozin and metformin compared to metformin monotherapy for weight loss in patients with class III obesity: a randomized controlled trial. Trials. 2020 Feb 14;21(1):186. doi: 10.1186/s13063-020-4121-x.

  PMID: 32059692 BACKGROUND

• Bolinder J, Ljunggren O, Johansson L, Wilding J, Langkilde AM, Sjostrom CD, Sugg J, Parikh S. Dapagliflozin maintains glycaemic control while reducing weight and body fat mass over 2 years in patients with type 2 diabetes mellitus inadequately controlled on metformin. Diabetes Obes Metab. 2014 Feb;16(2):159-69. doi: 10.1111/dom.12189. Epub 2013 Aug 29.

  PMID: 23906445 BACKGROUND

• Bolinder J, Ljunggren O, Kullberg J, Johansson L, Wilding J, Langkilde AM, Sugg J, Parikh S. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab. 2012 Mar;97(3):1020-31. doi: 10.1210/jc.2011-2260. Epub 2012 Jan 11.

  PMID: 22238392 BACKGROUND

• Mansuri Z, Makani R, Trivedi C, Adnan M, Vadukapuram R, Rafael J, Lodhi A, Reddy A. The role of metformin in treatment of weight gain associated with atypical antipsychotic treatment in children and adolescents: A systematic review and meta-analysis of randomized controlled trials. Front Psychiatry. 2022 Nov 15;13:933570. doi: 10.3389/fpsyt.2022.933570. eCollection 2022.

  PMID: 36458118 BACKGROUND

• Hegde NC, Mishra A, Maiti R, Mishra BR, Mohapatra D, Srinivasan A. Pharmacological interventions for antipsychotic-induced weight gain in schizophrenia: A network meta-analysis. Gen Hosp Psychiatry. 2024 Sep-Oct;90:12-21. doi: 10.1016/j.genhosppsych.2024.06.003. Epub 2024 Jun 11.

  PMID: 38878592 BACKGROUND

• de Silva VA, Suraweera C, Ratnatunga SS, Dayabandara M, Wanniarachchi N, Hanwella R. Metformin in prevention and treatment of antipsychotic induced weight gain: a systematic review and meta-analysis. BMC Psychiatry. 2016 Oct 3;16(1):341. doi: 10.1186/s12888-016-1049-5.

  PMID: 27716110 BACKGROUND

• Dayabandara M, Hanwella R, Ratnatunga S, Seneviratne S, Suraweera C, de Silva VA. Antipsychotic-associated weight gain: management strategies and impact on treatment adherence. Neuropsychiatr Dis Treat. 2017 Aug 22;13:2231-2241. doi: 10.2147/NDT.S113099. eCollection 2017.

  PMID: 28883731 BACKGROUND

• Musil R, Obermeier M, Russ P, Hamerle M. Weight gain and antipsychotics: a drug safety review. Expert Opin Drug Saf. 2015 Jan;14(1):73-96. doi: 10.1517/14740338.2015.974549. Epub 2014 Nov 15.

  PMID: 25400109 BACKGROUND

• Barton BB, Segger F, Fischer K, Obermeier M, Musil R. Update on weight-gain caused by antipsychotics: a systematic review and meta-analysis. Expert Opin Drug Saf. 2020 Mar;19(3):295-314. doi: 10.1080/14740338.2020.1713091. Epub 2020 Mar 12.

  PMID: 31952459 BACKGROUND

MeSH Terms

Conditions

Psychotic Disorders

Interventions

dapagliflozin; Metformin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Mohammed Al Alawi, MD, PhD

  Sultan Qaboos University

  STUDY CHAIR

Central Study Contacts

Said A Al Farsi, MD

CONTACT

00968 95783006; said.alfarsi96@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant and Assistant Professor

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 15, 2026
• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: June 10, 2026

Record last verified: 2026-06

Locations

OM (1)