Semaglutide to improve mood in adults with major depression who are overweight or have obesity

Is the GLP-1 Receptor Agonist Semaglutide Able to Alleviate Mood in Patients With Major Depressive Disorder and Overweight or Obesity

This trial will test if a once-weekly semaglutide injection added to usual medication can improve mood in adults with major depressive disorder who are overweight or have obesity.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 116 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Nordsjaellands Hospital (Academic / other)
• Locations: 1 site (Hillerød, Denmark)
• Trial ID: NCT07136714 on ClinicalTrials.gov

What this trial studies

This is a 26-week, randomized, double-blind, placebo-controlled trial enrolling 116 adults with unipolar major depressive disorder and BMI ≥27 kg/m2. Participants continue their usual depression medication and are randomized to once-weekly semaglutide (titrated to 2.4 mg) or matching placebo with visits at weeks 0, 4, 8, 12, 16, 20, 24, and 26. The primary outcome is change in depressive symptoms measured by the 12-item Major Depression Inventory (MDI) from baseline to week 26, with additional assessments including HAM-D17, weight, vitals, and questionnaires on activity, cognition, stress, reward, quality of life, alcohol use, and sleep. Safety, adherence, and adverse events are monitored throughout the treatment period.

Who should consider this trial

Good fit: Adults aged 18–65 with diagnosed unipolar major depressive disorder, HDRS-17 score ≥14, BMI ≥27 kg/m2, able to speak Danish, and willing to continue their usual medication are the ideal candidates.

Not a fit: People who are not overweight, who are pregnant or planning pregnancy, who have a known allergy to GLP-1 receptor agonists, significant medical contraindications, ongoing substance abuse, or who cannot attend clinic visits are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, semaglutide could reduce depressive symptoms and also address excess weight in people with major depressive disorder and overweight or obesity.

How similar studies have performed: Using GLP-1 receptor agonists for mood symptoms is a relatively new approach with some preliminary signals of metabolic and mood benefit, but randomized controlled evidence in depression is still limited.

Eligibility criteria

Inclusion Criteria:

1. Informed oral and written consent.
2. 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
3. Hamilton Depression Rating Scale, 17-items (HDRS-17)47 score ≥14,
4. Age 18 years to 65 years (both included)
5. Body mass index (BMI) ≥27 kg/m2
6. Able to speak and understand Danish

Exclusion Criteria:

1. 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
2. Coercive measures
3. 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)
4. Patients treated with corticosteroids or other hormone therapy (except oestrogens).
5. Any active substance abuse or dependence (except for nicotine)
6. Impaired hepatic function (plasma liver transaminases \>2 times upper normal limit).
7. Impaired renal function (serum creatinine \>150 μmol/l)
8. Cardiac problems defined as decompensated heart failure (NYHA class III/IV), unstable angina pectoris, and/or myocardial infarction within the last 12 months
9. Hypertension with systolic blood pressure \>180 mmHg or diastolic blood pressure \>100 mmHg
10. 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
11. Use of diabetes medication or weight-lowering pharmacotherapy e.g. semagultid within the preceding 3 months
12. Known type 1 and 2 diabetes or HbA1c\>48mmol/l
13. 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.
14. Any condition that the investigator feels would interfere with trial participation.

Where this trial is running

Hillerød, Denmark

• Mental Health Centre North Zealand — Hillerød, Denmark, Denmark (Recruiting)

Study contacts

• Principal investigator: Maj Vinberg, MD, PhD, DMSc — Mental Health Centre Copenhagen, Bispebjerg and Frederiksberg Hospital
• Study coordinator: Maj Vinberg, MD, DMSc

Conditions Major Depressive Disorder; GLP-1; Glucagon-like peptide 1; Semaglutide; Depression