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Study · Randomized controlled trial · n = 154 · 2026

7 results

Improved quality of life with semaglutide in schizophrenia: Secondary analyses from a randomized controlled trial.

Uhrenholt N, Ganeshalingam A, Arnfred S, Gæde P, Pedersen AK, Larsen PV, Frystyk J, Bilenberg N

Schizophrenia research16 Feb 2026

PMID41702353 (opens in a new tab)DOI10.1016/j.schres.2026.02.009 (opens in a new tab)PepBankPUB-41702353
Publisher pagePubMedAsk about this study
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Summary

BackgroundPeople with schizophrenia experience markedly reduced health-related quality of life (QoL), partly driven by obesity and metabolic dysregulation. Glucagon-like peptide-1 receptor agonists such as semaglutide induce substantial weight loss in the general population and in patients receiving antipsychotic medication. However, the extent to which semaglutide-associated weight loss mediates changes in QoL and symptom severity in schizophrenia remains unclear.MethodsThis secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity. Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks. Outcomes were the SF-36v2 Physical and Mental Component Summary scores (PCS, MCS) and the Positive and Negative Syndrome Scale, 6-item version (PANSS-6). Causal mediation analyses estimated natural direct and indirect effects of semaglutide via weight loss at weeks 15 and 30.ResultsSemaglutide improved PCS at weeks 15 and 30, with effect sizes exceeding the minimally important difference. Indirect effects via weight loss were positive but not statistically significant, although at week 30 approximately half of the total PCS effect was estimated to be mediated through weight change. No total or mediated effects were found for MCS. For PANSS-6, no meaningful mediation was observed.ConclusionsSemaglutide improved physical QoL in patients with schizophrenia, and weight loss may partially contribute to this effect. Longer-term studies are needed to determine whether mental QoL or symptom effects emerge beyond 30 weeks.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. 7 results from people.

  1. 01HumanRandomized controlled trialEfficacy outcome

    In adults with schizophrenia spectrum disorder, prediabetes and overweight or obesity, semaglutide improved the physical component summary score at week 15 versus placebo, with an effect size above the minimally important difference.

    In plain wordsIn adults with schizophrenia and overweight, semaglutide improved physical quality of life at week 15 more than placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseSF-36v2 Physical Component Summary at week 15
    Study

    n = 154

    Comparator
    Placebo
    Outcome group
    Quality of life · Whole body
    Studied dose
    Dose not stated · 30 weeksAs given in this study (human).

    Source sentences

    Summary
    Semaglutide improved PCS at weeks 15 and 30, with effect sizes exceeding the minimally important difference.
    2 context sentences
    Summary · context
    This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity.
    Summary · context
    Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks.
  2. 02HumanRandomized controlled trialEfficacy outcome

    In adults with schizophrenia spectrum disorder, prediabetes and overweight or obesity, semaglutide improved the physical component summary score at week 30 versus placebo, with an effect size above the minimally important difference.

    In plain wordsIn adults with schizophrenia and overweight, semaglutide improved physical quality of life at week 30 more than placebo.

    Peptide
    Semaglutide
    Outcome
    IncreaseSF-36v2 Physical Component Summary at week 30
    Study

    n = 154

    Comparator
    Placebo
    Outcome group
    Quality of life · Whole body
    Studied dose
    Dose not stated · 30 weeksAs given in this study (human).

    Source sentences

    Summary
    Semaglutide improved PCS at weeks 15 and 30, with effect sizes exceeding the minimally important difference.
    2 context sentences
    Summary · context
    This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity.
    Summary · context
    Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks.
  3. 03HumanRandomized controlled trialMechanism

    Indirect effects of semaglutide on the physical component summary score via weight loss were positive but not statistically significant.

    In plain wordsIn adults with schizophrenia, weight loss did not clearly explain the physical quality of life gain with semaglutide.

    Peptide
    Semaglutide
    Outcome
    No significant changeIndirect effect of semaglutide on PCS via weight loss
    Study

    n = 154

    Comparator
    Placebo
    Outcome group
    Quality of life · Whole body
    Studied dose
    Dose not stated · 30 weeksAs given in this study (human).

    Source sentences

    Summary
    Indirect effects via weight loss were positive but not statistically significant
    2 context sentences
    Summary · context
    This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity.
    Summary · context
    Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks.
  4. 04HumanRandomized controlled trialMechanism

    At week 30, approximately half of the total semaglutide effect on the physical component summary score was estimated to be mediated through weight change.

    In plain wordsIn adults with schizophrenia, about half of the physical quality of life gain with semaglutide was estimated to come through weight change.

    Peptide
    Semaglutide
    Outcome
    Not applicableShare of PCS effect mediated by weight change at week 30
    Study

    n = 154

    Comparator
    Placebo
    Outcome group
    Quality of life · Whole body
    Studied dose
    Dose not stated · 30 weeksAs given in this study (human).

    Source sentences

    Summary
    although at week 30 approximately half of the total PCS effect was estimated to be mediated through weight change
    2 context sentences
    Summary · context
    This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity.
    Summary · context
    Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks.
  5. 05HumanRandomized controlled trialEfficacy outcome

    Semaglutide had no total effect on the mental component summary score versus placebo.

    In plain wordsIn adults with schizophrenia, semaglutide did not change mental quality of life compared with placebo.

    Peptide
    Semaglutide
    Outcome
    No significant changeSF-36v2 Mental Component Summary, total effect
    Study

    n = 154

    Comparator
    Placebo
    Outcome group
    Quality of life · Mental health and mood
    Studied dose
    Dose not stated · 30 weeksAs given in this study (human).

    Source sentences

    Summary
    No total or mediated effects were found for MCS.
    2 context sentences
    Summary · context
    This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity.
    Summary · context
    Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks.
  6. 06HumanRandomized controlled trialMechanism

    No effect of semaglutide on the mental component summary score was mediated through weight loss.

    In plain wordsIn adults with schizophrenia, weight loss did not explain any mental quality of life change with semaglutide.

    Peptide
    Semaglutide
    Outcome
    No significant changeSF-36v2 Mental Component Summary, mediated effect via weight loss
    Study

    n = 154

    Comparator
    Placebo
    Outcome group
    Quality of life · Mental health and mood
    Studied dose
    Dose not stated · 30 weeksAs given in this study (human).

    Source sentences

    Summary
    No total or mediated effects were found for MCS.
    2 context sentences
    Summary · context
    This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity.
    Summary · context
    Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks.
  7. 07HumanRandomized controlled trialMechanism

    For PANSS-6, no meaningful mediation of the semaglutide effect through weight loss was observed.

    In plain wordsIn adults with schizophrenia, weight loss did not explain any change in symptom severity with semaglutide.

    Peptide
    Semaglutide
    Outcome
    No significant changePANSS-6 symptom severity, mediation via weight loss
    Study

    n = 154

    Comparator
    Placebo
    Outcome group
    Psychiatric symptoms · Mental health and mood
    Studied dose
    Dose not stated · 30 weeksAs given in this study (human).

    Source sentences

    Summary
    For PANSS-6, no meaningful mediation was observed.
    2 context sentences
    Summary · context
    This secondary analysis of a randomized, double-blind, placebo-controlled trial included 154 adults with schizophrenia spectrum disorder, prediabetes, and overweight or obesity.
    Summary · context
    Participants were randomized 1:1 to once-weekly semaglutide or placebo for 30 weeks.

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

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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