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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Metformin
  Tab 500-2000 mg/day (500 mg BD to 1000 mg BD)
• Препарат Antidepressant Therapy
  Sertraline 50 mg/day or Duloxetine 60 mg/day or Bupropion XL 150-300 mg/day

Первичные конечные точки

• Change in Severity of the depression [Срок оценки: 1 month]
• Change in BMI [Срок оценки: 3 months]

Вторичные конечные точки (6)

• Change in Blood Pressure [Срок оценки: 3 months]
• Change in Blood Sugar Levels [Срок оценки: 3 months]
• Change in Renal Function tests [Срок оценки: 3 months]
• Change in Liver Function tests [Срок оценки: 3 months]
• C - Reactive Proteins levels [Срок оценки: 3 months]
• Lipid Profile [Срок оценки: 3 months]

Критерии участия

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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Пакистан · 2 центра

• Pakistan Railway Hospital — Rawalpindi
• Afifa Siddique — Rawalpindi

Публикации

• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT07654179 · Riphah/IIMC/ IRB/26/1049

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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