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Study · Randomized controlled trial · n = 72 · 2026

4 results

Semaglutide and Effort-Based Decision-Making in Major Depressive Disorder: A Randomized Clinical Trial.

Gill H, Badulescu S, Shah H, Brudner RM, Phan L, Di Vincenzo JD, Tabassum A, Thanarajah SE, Llach CD, Rosenblat JD, McIntyre RS, Mansur RB

JAMA psychiatry1 Jul 2026

PMID42054055 (opens in a new tab)DOI10.1001/jamapsychiatry.2026.0594 (opens in a new tab)PepBankPUB-42054055
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Summary

The text of this summary is not shown here, because the article license does not allow reuse. Read it at the source (opens in a new tab)

Text rights: Publisher copyright. Results still quote short attributed sentences.

Results from this study4

4 results from studies that gave the peptide. 4 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with major depressive disorder, oral semaglutide increased willingness to exert physical effort at higher expected reward values compared with placebo.

    In plain wordsIn adults with depression, oral semaglutide made people more willing to put in effort for larger rewards than placebo did.

    Peptide
    Semaglutide
    Outcome
    IncreaseWillingness to exert effort for higher expected reward value (EEfRT)
    Study

    n = 72

    Comparator
    Placebo
    Analysis
    Secondary
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    14 mg · oral · 16 weeksAs given in this study (human).

    Source sentences

    Summary
    Semaglutide-treated participants exhibited a pattern of increased willingness to exert physical efforts with higher expected values of reward (treatment × visit × expected value interaction: χ2 = 12.024; P = .02).
    3 context sentences
    Summary · context
    This study was a 16-week, double-blind, placebo-controlled, parallel-group randomized clinical trial.
    Summary · context
    A total of 72 participants with a diagnosis of MDD and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or higher were randomized to oral semaglutide (n = 35) or placebo (n = 37).
    Summary · context
    Patients were randomized 1:1 to receive placebo or oral semaglutide, 14 mg (initiated at 4 mg and titrated using a 4-week dose-escalation regimen), adjunctive to their treatment as usual.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In adults with major depressive disorder, oral semaglutide significantly reduced sensitivity to effort compared with placebo.

    In plain wordsIn adults with depression, oral semaglutide reduced how costly effort felt compared with placebo.

    Peptide
    Semaglutide
    Outcome
    DecreaseSensitivity to effort
    Study

    n = 72

    Comparator
    Placebo
    Analysis
    Secondary
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    14 mg · oral · 16 weeksAs given in this study (human).

    Measurements

    Beta, sensitivity to effort
    −1.737
    semaglutide vs placebo

    Source sentences

    Summary
    Sensitivity to effort was significantly reduced by treatment with semaglutide (β = -1.737; P = .03), whereas there was no treatment effect on sensitivity to probability (β = -0.776; P = .51).
    3 context sentences
    Summary · context
    This study was a 16-week, double-blind, placebo-controlled, parallel-group randomized clinical trial.
    Summary · context
    A total of 72 participants with a diagnosis of MDD and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or higher were randomized to oral semaglutide (n = 35) or placebo (n = 37).
    Summary · context
    Patients were randomized 1:1 to receive placebo or oral semaglutide, 14 mg (initiated at 4 mg and titrated using a 4-week dose-escalation regimen), adjunctive to their treatment as usual.
  3. 03HumanRandomized controlled trialEfficacy outcome

    In adults with major depressive disorder, oral semaglutide had no treatment effect on sensitivity to probability compared with placebo.

    In plain wordsIn adults with depression, oral semaglutide did not change sensitivity to probability compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeSensitivity to probability
    Study

    n = 72

    Comparator
    Placebo
    Analysis
    Secondary
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    14 mg · oral · 16 weeksAs given in this study (human).

    Measurements

    Beta, sensitivity to probability
    −0.776
    semaglutide vs placebo

    Source sentences

    Summary
    whereas there was no treatment effect on sensitivity to probability (β = -0.776; P = .51).
    3 context sentences
    Summary · context
    This study was a 16-week, double-blind, placebo-controlled, parallel-group randomized clinical trial.
    Summary · context
    A total of 72 participants with a diagnosis of MDD and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or higher were randomized to oral semaglutide (n = 35) or placebo (n = 37).
    Summary · context
    Patients were randomized 1:1 to receive placebo or oral semaglutide, 14 mg (initiated at 4 mg and titrated using a 4-week dose-escalation regimen), adjunctive to their treatment as usual.
  4. 04HumanRandomized controlled trialMechanism

    In adults with major depressive disorder, computational modelling indicated that semaglutide changed choice behavior through reduced effort discounting.

    In plain wordsIn adults with depression, modelling suggested semaglutide changed choices by making effort feel less costly.

    Peptide
    Semaglutide
    Outcome
    DecreaseEffort discounting in computational modelling
    Study

    n = 72

    Comparator
    Placebo
    Analysis
    Secondary
    Outcome group
    Anxiety and mood · Mental health and mood
    Studied dose
    14 mg · oral · 16 weeksAs given in this study (human).

    Source sentences

    Summary
    Computational modeling indicated that semaglutide's effects on choice behavior were a result of reduced effort discounting.
    3 context sentences
    Summary · context
    This study was a 16-week, double-blind, placebo-controlled, parallel-group randomized clinical trial.
    Summary · context
    A total of 72 participants with a diagnosis of MDD and a body mass index (calculated as weight in kilograms divided by height in meters squared) of 25 or higher were randomized to oral semaglutide (n = 35) or placebo (n = 37).
    Summary · context
    Patients were randomized 1:1 to receive placebo or oral semaglutide, 14 mg (initiated at 4 mg and titrated using a 4-week dose-escalation regimen), adjunctive to their treatment as usual.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Registered trials1

Trials this study reports on, or that list this study as a reference. Registry data from ClinicalTrials.gov.

1 trial · 1 completed · source ClinicalTrials.gov (opens in a new tab)

CompletedPhase 2NCT04466345

Semaglutide for the Treatment of Cognitive Dysfunction in Major Depressive Disorder

University Health Network, Toronton = 726 Oct 2021 to 27 Dec 2024

Major Depressive Disorder

Trial pageClinicalTrials.govUpdated 2 Oct 2025

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 2Current

    11 Oct 2026, 00:04 UTC

    Study results updated

  2. Version 1

    9 Oct 2026, 03:06 UTC

    First added · source update from Europe PMC

Subjects

Terms as the source lists them.

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