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

What Was Tested

The trial (phase 4) is built around Semaglutide.

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.

It had two arms (groups): Semaglutide (experimental) and Placebo (placebo comparator).

Saline s.c. once-weekly.

The registry classes the interventions as drug.

More on the Plan

This 26 week, randomized, double-blinded, placebo-controlled clinical trial investigate effects of semaglutide once-weekly vs. placebo on depressive symptoms in patients with unipolar disorder and comorbid obesity or overweight aged 18 years to 65 years.

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 week 0 to week 26.

Participants will be randomized to receive once-weekly injection of either semaglutide or placebo.

Assessments will be conducted at weeks 0, 4, 8, 12, 16, 20, 24, and 26.

Who Took Part

116 planned participants were the target.

It was open to people of any sex aged from 18 years up to 65 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Informed oral and written consent. 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.

The full record lists 6 inclusion and 14 exclusion criteria; among the exclusions: coercive measures; patients treated with corticosteroids or other hormone therapy (except oestrogens); any active substance abuse or dependence (except for nicotine).

How the Study Was Run

The set-up was randomized, parallel-group and quadruple-blind.

Random assignment meant chance, not the researchers, decided who got Semaglutide and who got the comparison, which limits bias.

The Semaglutide group and the comparison group ran side by side rather than switching.

Blinding on both sides kept the participants and researchers unaware of who received Semaglutide.

Those kept unaware of assignments: participant, care provider, investigator and outcomes assessor.

It started in 2025-09-11 with completion listed for 2027-09.

It ran at 1 site in Denmark.

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Change in depressive symptoms (time frame: From baseline to 26 weeks of treatment).

It also tracked 5 secondary outcomes, for example Glycaemic control parameters (blood sampling), Body weight, Waist circumference, Hamilton Depression Rating Scale, 17-items (HDRS-17) score and Functioning assessment short test (FAST) score.

What This Means in Plain Language

Put simply, this is a phase 4, randomized trial of Semaglutide in 116 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Semaglutide compound page, all human trials.