AzTrials
AzTrials

DepressionNCT07654179

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

A study testing Metformin and Antidepressant Therapy in people with Depression and Depressive Disorder, run by Riphah International University at 2 sites in Pakistan.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Any ageHealthy volunteers can take part
What is being tested?
Metformin and Antidepressant Therapy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
2 sitesPakistan
Study dates
17 Jun 2026to 11 Jun 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Any age
  • All sexes
  • Healthy volunteers accepted
  • Child, Adult, Older adult

INCLUSION CRITERIA Group I: Normal Controls Group II: Depression Group III: Obesity

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)

EXCLUSION CRITERIA Groups I-III: Negative Controls (Normal: no depression and Obesity for SNP comparison only)

  • Age less than 18
  • Dementia/ Mentally impaired who can not fill self report performas for inclusion criteria

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
  • DM
  • Untreated hypothyroidism
  • History of myocardial infarction or stroke
  • Symptomatic peripheral arterial disease
  • Monogenic familial hypercholesterolemia

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

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

Pakistan2 sites, 2 recruiting
  • Pakistan Railway Hospital

    Rawalpindi, Punjab Province, 44000

    Siddique, MBBS, M.Phil, +923175441910, dr.afifa.siddique@gmail.com

    Farooq, MBBS, M.Phil, +92 333 5244374, drafifa.one@gmail.com

    Recruiting
  • Afifa Siddique

    Rawalpindi, Punjab Province

    AFIFA Siddique, PhD Scholar, MBBS, MPhil, +923175441910, Dr.afifa.siddique@gmail.com

    Afifa Siddique, MBBS, Mphil, +923448568632, drafifa.one@gmail.com

    Recruiting

Other trials in Pakistan

About this study

Official title: Efficacy of Metformin With Antidepressant Medication as Adjunct Therapy in Depression-obesity Ccomorbidity and Ssociation With NEGR1/RPL31P12 Variants Based on Genotyping

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.

Read the detailed description

There is a substantial percentage of the Pakistani population who are both overweight/obese and depressed, with estimates from clinical samples averaging 25%. So, the personalized treatment approach for depression and obesity needs to be explored.

Obesity and depression commonly coexist and are associated with poorer health outcomes. Metformin, widely used for metabolic disorders and obesity, has shown potential antidepressant effects. However, evidence on its use as an adjunct to antidepressant therapy in patients with depression-obesity comorbidity remains limited, and the influence of genetic variants on treatment response is not well understood. This study aims to evaluate the effectiveness of adjunctive metformin and its association with NEGR1 and RPL31P12 genetic variants in this population.

Being tested
Metformin, Antidepressant Therapy
Medical subject headings
Depression, Depressive Disorder, Overweight, Obesity

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

    Also called Trade names: Glucophage, Neodipar

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

  • Antidepressant TherapyDrug

    Also called Sertraline hydrochloride, Bupropion hydrochloride,

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

Study groups in NCT07654179
Study groupRoleWhat they receive
Antidepressant MonotherapyActive comparatorTab Sertraline 50 mg/day or Cap Duloxetine 60 mg/day or Tab Bupropion XL 150-300 mg/day
Receives: Drug: Antidepressant Therapy
Adjunctive Metformin TherapyExperimentalTab Sertraline 50 mg/day + Metformin or Cap Duloxetine 60 mg/day + Metformin or Tab Bupropion XL 150-300 mg/day + Metformin
Receives: Drug: Metformin; Drug: Antidepressant Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 1 month

  2. 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.

    Measured: 3 months

Secondary outcomes (6)
  1. Change in Blood Pressure

    Change in Blood Pressure: Blood pressure will be measured in mmHg at baseline, 14 days, 28 days, one month and 3 months.. The outcome will be assessed as the change in systolic and diastolic blood pressure from baseline. Normal blood pressure is <120/80 mmHg, elevated blood pressure is 120-129/<80 mmHg, and high blood pressure is ≥130/80 mmHg. A reduction in blood pressure values from baseline will indicate improvement in cardiovascular health status.

    Measured: 3 months

  2. Change in Blood Sugar Levels

    Change in Blood Sugar: Blood glucose levels will be measured at baseline, 14 days, 28 days, one month and 3 months. The outcome will be assessed as the change in blood glucose from baseline. Normal fasting blood glucose is 70-99 mg/dL, prediabetes is 100-125 mg/dL, and diabetes is ≥126 mg/dL. A reduction in blood glucose levels toward the normal range will indicate improvement in glycemic control, whereas increase will be monitored for safety

    Measured: 3 months

  3. Change in Renal Function tests

    Change in Renal Function Tests: Renal function will be monitored by measuring serum creatinine and blood urea levels at baseline and study completion. The outcome will be assessed as the change in these parameters from baseline. Normal serum creatinine is approximately 0.6-1.2 mg/dL, while values >1.2 mg/dL may indicate impaired renal function. Normal blood urea is approximately 15-40 mg/dL, while values >40 mg/dL may suggest reduced kidney function or impaired renal clearance. An increase in serum creatinine or blood urea from baseline will be considered indicative of deterioration in renal function, whereas stable values within the normal range will indicate preserved renal function.

    Measured: 3 months

  4. Change in Liver Function tests

    Change in Liver Function Tests (LFTs): Liver function will be monitored at baseline and study completion. The outcome will be assessed as the change in liver enzyme levels and bilirubin from baseline.

    Alanine Aminotransferase (ALT): Normal 7-56 U/L; elevated >56 U/L may indicate liver injury.

    Aspartate Aminotransferase (AST): Normal 10-40 U/L; elevated >40 U/L may indicate hepatic or muscle injury.

    Alkaline Phosphatase (ALP): Normal 44-147 U/L; elevated >147 U/L may suggest cholestatic liver disease or biliary obstruction.

    Total Bilirubin: Normal 0.2-1.2 mg/dL; elevated >1.2 mg/dL may indicate impaired liver function or biliary obstruction.

    Albumin: Normal 3.5-5.0 g/dL; decreased <3.5 g/dL may indicate impaired hepatic synthetic function.

    Measured: 3 months

  5. C - Reactive Proteins levels

    Change in C-Reactive Protein (CRP) Levels: CRP levels will be measured at baseline and study completion to assess systemic inflammation. The outcome will be assessed as the change in CRP levels from baseline.

    Normal: < 3 mg/L Mildly elevated: 3-10 mg/L Moderately elevated: 10-50 mg/L Markedly elevated: > 50 mg/L Severely elevated: > 100 mg/L

    Decrease in CRP level: Indicates reduction in systemic inflammation. Stable CRP within normal range (< 3 mg/L): Indicates absence of significant inflammation.

    Increase in CRP above normal range: Suggests worsening or persistent inflammatory activity.

    Measured: 3 months

  6. Lipid Profile

    It will be measured at baseline and study completion to monitor safety of combination therapy.

    Total Cholesterol (TC): Desirable: < 200 mg/dL, Borderline high: 200-239 mg/dL, High: ≥ 240 mg/dL Low-Density Lipoprotein Cholesterol (LDL-C): Optimal: < 100 mg/dL, Near optimal: 100-129 mg/dL, Borderline high: 130-159 mg/dL, High: 160-189 mg/dL, Very high: ≥ 190 mg/dL High-Density Lipoprotein Cholesterol (HDL-C): Low: < 40 mg/dL (men), < 50 mg/dL (women), Protective: ≥ 60 mg/dL Triglycerides (TG): Normal: < 150 mg/dL, Borderline high: 150-199 mg/dL, High: 200-499 mg/dL, Very high: ≥ 500 mg/dL

    Interpretation:

    Decrease in TC, LDL-C, and TG levels indicates improvement in lipid metabolism. Increase in HDL-C levels indicates a favorable cardiovascular risk profile. Lipid values remaining within the normal range throughout the study will be considered indicative of metabolic safety of the combination therapy.

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jun 2026
  2. Study start17 Jun 2026
  3. Primary completion11 Jun 2027 (estimated)
  4. Study completion11 Jun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07654179
Sponsor's protocol ID
Riphah/IIMC/ IRB/26/1049
Status last verified
Aug 2026
First submitted
13 Jun 2026
Last updated
7 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 40096719
  • 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.

    PubMed 27923415
  • 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.

    PubMed 39894309
  • 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.

    PubMed 41727810

Questions about this trial

What is this clinical trial studying?

A study testing Metformin and Antidepressant Therapy in people with Depression and Depressive Disorder, run by Riphah International University at 2 sites in Pakistan.

The full registered description is in the About this study section and the official record.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 7 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Afifa Siddique, PhD Scholar, MBBS, M.Phil (+923175441910, dr.afifa.siddique@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Severity of the depression (time frame: 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07654179, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Aug 2026.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in