Does Semaglutide Improve Depressive Symptoms in Patients With Major Depressive Disorder and Overweight or Obesity

NCT07136714 | Recruiting Phase 4 DMC

• 1 other identifier: 2024-511734-13-04
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

This 26-week long, double-blinded randomized clinical trial aims to investigate the effects of semaglutide once-weekly vs. placebo on depressive symptoms in 116 patients with Major Depressive Disorder (MDD) and co-existing overweight or obesity. The treatment will be an add-on treatment to the patient's usual medication. The investigators hypothesize that adjunctive treatment with semaglutide, will lead to a significant improvement in mood compared to placebo in patients with MDD and overweight or obesity. The primary endpoint is the change in depressive symptoms measured as difference in the 12-item self-report mood questionnaire Major Depression Inventory (MDI) from start to follow-up after 26 weeks. The MDI measures the extent to which symptoms of depression have been present in the past two weeks.

Conditions

Major Depressive Disorder

Keywords

GLP-1; Glucagon-like peptide 1; Semaglutide; Depression

Outcome Measures

Primary Outcomes (1)

• Change in depressive symptoms

  Change in depressive symptoms measured by the Major Depression Inventory (MDI; 12-item self-report mood questionnaire). The scale ranges from 0 to 50, with higher scores indicating worse outcome.

  From baseline to 26 weeks of treatment

Secondary Outcomes (5)

• Glycaemic control parameters (blood sampling)

  From baseline to 26 weeks of treatment

• Body weight

  From baseline to 26 weeks

• Waist circumference

  From baseline to 26 weeks of treatment

• Hamilton Depression Rating Scale, 17-items (HDRS-17) score

  From baseline to 26 weeks of treatment

• Functioning assessment short test (FAST) score

  From baseline to 26 weeks of treatment

Study Arms (2)

Semaglutide

EXPERIMENTAL

Wegovy once--weekly s.c titrated to max dose of 2.4 mg

Drug: Semaglutide Injectable Product

Placebo

PLACEBO COMPARATOR

Saline s.c. once-weekly

Drug: Placebo

Interventions

Semaglutide Injectable Product DRUG

Semaglutide (Wegovy) once-weekly injection s.c

Semaglutide

Placebo DRUG

Placebo (BD Posiflush) once-weekly injection s.c

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed oral and written consent.
• Diagnosed with unipolar disorder according to the criteria of ICD10 (International Classification of Diseases, World Health Organization (WHO)) or the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the American Psychiatric Association
• Hamilton Depression Rating Scale, 17-items (HDRS-17)47 score ≥14,
• Age 18 years to 65 years (both included)
• Body mass index (BMI) ≥27 kg/m2
• Able to speak and understand Danish

You may not qualify if:

• Any significant medical disorder or conditions that contraindicate the investigational drug, e.g., pregnancy, presence of known allergy GLP-1 receptor agonists, severe neurological disorder, on-going drug, or alcohol abuse
• Coercive measures
• Females of childbearing potential who are pregnant, breast-feeding or have the intention of becoming pregnant within the next 9 months (26 weeks plus two months after discontinuation of semaglutide), or are not using contraceptives (during the whole study period) considered as highly effective (combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device - IUD, IUS, bilateral tubal occlusion, vasectomised partner, sexual abstinence)
• Patients treated with corticosteroids or other hormone therapy (except oestrogens).
• Any active substance abuse or dependence (except for nicotine)
• Impaired hepatic function (plasma liver transaminases \>2 times upper normal limit).
• Impaired renal function (serum creatinine \>150 μmol/l)
• Cardiac problems defined as decompensated heart failure (NYHA class III/IV), unstable angina pectoris, and/or myocardial infarction within the last 12 months
• Hypertension with systolic blood pressure \>180 mmHg or diastolic blood pressure \>100 mmHg
• Impaired pancreatic function (acute or chronic pancreatitis and/or plasma amylase \>2 times upper normal limit). Receiving any experimental or pre-marketing drug within the last 3 months
• Use of diabetes medication or weight-lowering pharmacotherapy e.g. semagultid within the preceding 3 months
• Known type 1 and 2 diabetes or HbA1c\>48mmol/l
• Suicidal behaviour as judged by the investigator and based on clinical evaluation. At all contact with patient attendance (please see Table 1) possible suicidality will be evaluatedaccording to the guidelines. If the patient is evaluated as suicidal, the person will be excluded from the study and evaluated by a senior consultant in psychiatry, who will take further action.
• Any condition that the investigator feels would interfere with trial participation.

Sponsors & Collaborators

• Nordsjaellands Hospital: lead

Study Sites (1)

Mental Health Centre North Zealand

Hillerød, Denmark, 3400, Denmark

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Maj Vinberg, MD, PhD, DMSc

  Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Maj Vinberg, MD, DMSc

CONTACT

+ 45 38 64 32 27; maj.vinberg@regionh.dk

Christoffer Stanislaus, MD, ph.d.-student

CONTACT

Christoffer.stanislaus@regionh.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, DMSc, Professor

Study Record Dates

• First Submitted: August 7, 2025
• First Posted: August 22, 2025
• Study Start: September 11, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027
• Last Updated: February 6, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

DK (1)