Metformin as Adjunct Therapy in Depression-obesity Comorbidity: Clinical and Genetic Evaluation

NCT07654179 | Recruiting

• 1 other identifier: Riphah/IIMC/ IRB/26/1049
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

The patients with depression and obesity will receive add-on metformin with antidepressant therapy, which may result in greater improvement in depressive symptoms and BMI reduction compared to antidepressant monotherapy. NEGR1/RPL31P12 gene polymorphisms may influence the comparative efficacy of antidepressant monotherapy versus combination therapy (antidepressant + metformin) in Pakistani patients. Patients with certain variants may respond better or worse to antidepressants and may have different weight outcomes.

Conditions

Depression; Depressive Disorder; Overweight or Obesity; Depressive Symptoms

Outcome Measures

Primary Outcomes (2)

• Change in Severity of the depression

  The change in the total PHQ-9 score between baseline and 4-weeks follow-up is the primary outcome measure. This measure is a patient-rated inventory of depressive symptoms. All items are scored on scales ranging from 0-3 and the sum of the scores provides the total score for the measure. On this scale, higher scores indicate poorer outcomes. Scores 9-19 and 20-27 are considered moderate and severe depression respectively.

  1 month

• Change in BMI

  Change in Body Mass Index (BMI): BMI will be measured at baseline and study completion and calculated as weight in kilograms divided by height in meters squared (kg/m²). The outcome will be assessed as the change in BMI from baseline. Asian BMI Classification: Underweight: \< 18.5 kg/m² Normal weight: 18.5-22.9 kg/m² Overweight: 23.0-24.9 kg/m² Obesity Class I: 25.0-29.9 kg/m² Obesity Class II: ≥ 30.0 kg/m² BMI reduction \< 1 kg/m²: Minimal change BMI reduction ≥ 1 kg/m²: Clinically meaningful improvement Weight loss ≥ 5% of baseline body weight: Clinically significant weight reduction associated with metabolic health benefits. A decrease in BMI from baseline and/or movement to a lower BMI category will be considered indicative of improvement in obesity-related outcomes.

  3 months

Secondary Outcomes (6)

• Change in Blood Pressure

  3 months

• Change in Blood Sugar Levels

  3 months

• Change in Renal Function tests

  3 months

• Change in Liver Function tests

  3 months

• C - Reactive Proteins levels

  3 months

Other Outcomes (2)

• NEGR1 Polymorphism

  1 month

• RPL31P12

  1 month

Study Arms (2)

Antidepressant Monotherapy

ACTIVE COMPARATOR

Tab Sertraline 50 mg/day or Cap Duloxetine 60 mg/day or Tab Bupropion XL 150-300 mg/day

Drug: Antidepressant Therapy

Adjunctive Metformin Therapy

EXPERIMENTAL

Tab Sertraline 50 mg/day + Metformin or Cap Duloxetine 60 mg/day + Metformin or Tab Bupropion XL 150-300 mg/day + Metformin

Drug: Metformin; Drug: Antidepressant Therapy

Interventions

Antidepressant Therapy DRUG

Sertraline 50 mg/day or Duloxetine 60 mg/day or Bupropion XL 150-300 mg/day

Also known as: Sertraline hydrochloride, Bupropion hydrochloride,

Adjunctive Metformin Therapy; Antidepressant Monotherapy

Metformin DRUG

Tab 500-2000 mg/day (500 mg BD to 1000 mg BD)

Also known as: Trade names: Glucophage, Neodipar

Adjunctive Metformin Therapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Group IV and V:
• Age ≥ 18 years
• Both males and females
• Recurrent depressive disorder (6A71) according to ICD-11,
• Asian cut off: Obese and overweight (BMI \< 23)
• BDI score ≥ 13 or PHQ score ≥ 4
• Either medication-naïve or medication-free for at least 2 weeks before enrollment, or the patient did not take antidepressants during the last 7 days before study entry (discontinuation of effective medication to enable study participation is prohibited)
• In case of non-psychotropic medication: The patient received stable pharmacological medication for at least 14 days before study entry (any changes in medication dose or frequency of therapy must be answered with no)

You may not qualify if:

• Age less than 18
• Group IV: Positive Control (RCT patients)
• Patients with comorbid conditions (HTN, CKD) if taking any drug for that condition.
• The patient is not an employee of the investigator study site, or a family member of the employees or the investigator, or otherwise dependent on the sponsor, the investigator, or the investigator study site.
• The patient did not participate in other interventional trials during the 6 months before and at the time of this trial. The patient does not have a history of non-response to antidepressants included in the study.
• The patient has not given birth within the 6 months before study entry and is not breastfeeding
• The patient did not receive treatment with ketamine, irreversible MAO inhibitor (e.g. tranylcypromine), electroconvulsive therapy (ECT) or other stimulatory treatments in the index episode.
• The patient is not diagnosed with dementia and does not have moderate or severe impairment of general cognitive function according to clinical impression.
• The patient does not meet the criteria for alcohol use disorder (DSM-5: 303.90; ICD-10: F10.20) or substance use disorder (DSM-5: 304; ICD-10: F11.20 - F19.20) in DSM-5, and a urine/serum drug screening is negative (except for benzodiazepines and opiates).
• The patient does not have:
• A known allergy or contraindication against antidepressants included in the study
• History of suicidal tendencies
• Uncontrolled hepatic disorder, renal or cardiovascular disease
• Untreated hypothyroidism
• History of myocardial infarction or stroke

Sponsors & Collaborators

• Riphah International University: lead

Study Sites (2)

Pakistan Railway Hospital

Rawalpindi, Punjab Province, 44000, Pakistan

RECRUITING

Afifa Siddique

Rawalpindi, Punjab Province, Pakistan

RECRUITING

Related Publications (4)

• Siddique A, Naeem U, Masood Khokhar M, Waheed Syed A, Iftikhar J, Amjad A. Impact of Demographic Factors on the Treatment Response of Antidepressant Therapy: A Descriptive Cohort Study from Pakistan. Tunis Med. 2025 Feb 5;103(2):201-205. doi: 10.62438/tunismed.v103i2.5280.

  PMID: 40096719 RESULT

• Ninomiya-Baba M, Matsuo J, Sasayama D, Hori H, Teraishi T, Ota M, Hattori K, Noda T, Ishida I, Shibata S, Kunugi H. Association of body mass index-related single nucleotide polymorphisms with psychiatric disease and memory performance in a Japanese population. Acta Neuropsychiatr. 2017 Oct;29(5):299-308. doi: 10.1017/neu.2016.66. Epub 2016 Dec 7.

  PMID: 27923415 RESULT

• Cheng YY, Yao Q, Miao Y, Guan W. Metformin as a potential antidepressant: Mechanisms and therapeutic insights in depression. Biochem Pharmacol. 2025 Mar;233:116773. doi: 10.1016/j.bcp.2025.116773. Epub 2025 Jan 31.

  PMID: 39894309 RESULT

• Choi WS, Song MK, Seo M, Woo YS, Bahk WM. Comparative efficacy and safety of liraglutide versus metformin, naltrexone/bupropion, and phentermine-topiramate in psychiatric patients. Ther Adv Psychopharmacol. 2026 Feb 18;16:20451253261419609. doi: 10.1177/20451253261419609. eCollection 2026.

  PMID: 41727810 RESULT

MeSH Terms

Conditions

Depression; Depressive Disorder; Overweight; Obesity

Interventions

Metformin; Sertraline; Bupropion

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Mood Disorders; Mental Disorders; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; 1-Naphthylamine; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Propiophenones; Ketones

Study Officials

• Afifa,Siddique, PhD Scholar, MBBS, M.Phil

  Islamic International Medical College, Riphah International University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Afifa Siddique, PhD Scholar, MBBS, M.Phil

CONTACT

+923175441910; dr.afifa.siddique@gmail.com

Tayaba Farooq, MBBS, M.Phil

CONTACT

+92 333 5244374; drafifa.one@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Total 5 groups: 1. Three groups will be negative control, assessed for genetic variants only, and not included in RCT. normal subjects, depression, or obesity (each n=90). 2. Comorbid depression-obesity will be positive control. RCT will be conducted on this group (n=180), and they will be divided into two main groups. Group 1 (n = 90) will receive sertraline, duloxetine, or bupropion monotherapy (groups A, B, and C - 30 patients each). Group 2 (n = 90) will similarly be subdivided into three groups A', B', and C' (30 patients each). They will receive sertraline, duloxetine, or bupropion in combination with metformin. Group 2 combinations: Tab Metformin + Tab sertraline Tab Metformin + Cap. duloxetine Tab Metformin + Tab bupropion

Study Record Dates

• First Submitted: June 13, 2026
• First Posted: June 17, 2026
• Study Start: June 17, 2026
• Primary Completion (Estimated): June 11, 2027
• Study Completion (Estimated): June 11, 2027
• Last Updated: August 7, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

PA (2)