Semaglutide and Early-Stage Metabolic Abnormalities in Individuals With Schizophrenia Spectrum Disorders: A Randomized Clinical Trial.

Sass MR, Klausen MK, Schwarz CR, Rasmussen L, Giver MEB, Hviid M, Schilling C, Zamorski A, Jensen A, Gefke M, Storgaard H, Oturai PS and 8 more

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Kjaer A, Hartmann B, Holst JJ, Ekstrøm CT, Vinberg M, Correll CU, Vilsbøll T, Fink-Jensen A

JAMA psychiatry1 Feb 2026Cited by 13 (Europe PMC)

PMID41335431DOI10.1001/jamapsychiatry.2025.3639PepBankPUB-41335431

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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 study11

11 results from studies that gave the peptide. 11 results from people.

01HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine and early glycemic abnormalities, semaglutide reduced HbA1c more than placebo at week 26.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, semaglutide lowered HbA1c more than placebo after 26 weeks.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change at week 26
Study
n = 73
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Measurements
HbA1c mean difference
−0.25%
semaglutide minus placebo
Source sentences
Summary
At week 26, semaglutide significantly reduced HbA1c level compared with placebo (mean difference, -0.25%; 95% CI, -0.33 to -0.16; P < .001)
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543101
02HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, more semaglutide recipients than placebo recipients reached low-risk HbA1c levels below 5.4%.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, far more people on semaglutide than on placebo reached a low-risk HbA1c level.
Peptide
Semaglutide
Outcome
IncreaseParticipants reaching low-risk HbA1c below 5.4%
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Measurements
Participants with HbA1c <5.4%
43%
semaglutide
Participants with HbA1c <5.4%
3%
placebo
Source sentences
Summary
43% of participants (12 of 28) treated with semaglutide achieved low-risk HbA1c levels (<5.4%) vs 3% with placebo
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543102
03HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, semaglutide reduced body weight more than placebo.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, semaglutide lowered body weight more than placebo.
Peptide
Semaglutide
Outcome
DecreaseBody weight change
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Body weight · Metabolic and weight
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Measurements
Body weight difference
−9.2 kg
semaglutide minus placebo
Source sentences
Summary
Greater reductions in body weight (-9.2 kg; 95% CI, -13.3 to -5.1 kg; P < .001)
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543103
04HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, semaglutide reduced waist circumference more than placebo.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, semaglutide reduced waist size more than placebo.
Peptide
Semaglutide
Outcome
DecreaseWaist circumference change
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Body weight · Metabolic and weight
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Measurements
Waist circumference difference
−7 cm
semaglutide minus placebo
Source sentences
Summary
waist circumference (-7.0 cm; 95% CI, -10.6 to -3.3 cm; P < .001)
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543104
05HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, semaglutide reduced fat mass more than placebo.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, semaglutide reduced body fat more than placebo.
Peptide
Semaglutide
Outcome
DecreaseFat mass change
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Body weight · Metabolic and weight
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Measurements
Fat mass difference
−6.1 kg
semaglutide minus placebo
Source sentences
Summary
fat mass (-6.1 kg; 95% CI, -10.2 to -1.9 kg; P = .006)
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543105
06HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, semaglutide did not change lipid levels versus placebo.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, semaglutide did not change blood fat levels compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeLipid levels
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Lipids · Cardiovascular
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
No differences in lipid levels, liver function, blood pressure, or psychiatric symptoms were observed.
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543106
07HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, semaglutide did not change liver function versus placebo.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, semaglutide did not change liver function compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeLiver function
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Liver fat and liver function · Liver
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
No differences in lipid levels, liver function, blood pressure, or psychiatric symptoms were observed.
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543107
08HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, semaglutide did not change blood pressure versus placebo.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, semaglutide did not change blood pressure compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeBlood pressure
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Blood pressure · Cardiovascular
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
No differences in lipid levels, liver function, blood pressure, or psychiatric symptoms were observed.
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543108
09HumanRandomized controlled trialEfficacy outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, semaglutide did not change psychiatric symptoms versus placebo.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, semaglutide did not change psychiatric symptoms compared with placebo.
Peptide
Semaglutide
Outcome
No significant changePsychiatric symptoms
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
No differences in lipid levels, liver function, blood pressure, or psychiatric symptoms were observed.
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543109
10HumanRandomized controlled trialSafety outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, gastrointestinal adverse events with semaglutide were common but mild and transient.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, stomach and bowel side effects with semaglutide were common but mild and short-lived.
Peptide
Semaglutide
Outcome
Not applicableGastrointestinal adverse events
Study
n: not reported in source
Analysis
Exploratory
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
Gastrointestinal adverse events were common but mild and transient
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543110
11HumanRandomized controlled trialSafety outcome
In adults with schizophrenia spectrum disorders on clozapine or olanzapine, psychiatric adverse events were similar across the semaglutide and placebo groups.
In plain wordsIn adults with schizophrenia on clozapine or olanzapine, psychiatric side effects were similar with semaglutide and with placebo.
Peptide
Semaglutide
Outcome
No significant changePsychiatric adverse events
Study
n: not reported in source
Comparator
Placebo
Analysis
Exploratory
Outcome group
Adverse events · Mental health and mood
Studied dose
1 mg · subcutaneous · 26 weeksAs given in this study (human).
Source sentences
Summary
psychiatric adverse events were similar across groups.
3 context sentences(design, population, supporting numbers)
Summary · context
To evaluate the efficacy of adjunctive semaglutide on glycemic control, weight-associated outcomes, and cardiometabolic risk factors in individuals with schizophrenia spectrum disorders receiving clozapine or olanzapine and exhibiting early glycemic abnormalities.
Summary · context
Screening individuals were aged 18 to 65 years with schizophrenia spectrum disorders and clozapine or olanzapine treatment initiated within the past 5 years.
Summary · context
Participants received once-weekly subcutaneous semaglutide (1 mg) or a matching placebo, administered adjunctively to SGA therapy for 26 weeks.
Report a problemFND-4133543111

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

Status unknownPhase 4NCT04892199

Does GLP-1RA Prevent Deterioration of Metabolic State in Prediabetic and Diabetic Patients Treated With Antipsychotic Medication?

Anders Fink-Jensen, MD, DMScin = 1041 Sept 2021 to est. 1 Aug 2026

Metabolic Disturbance · Schizophrenia · Type 2 Diabetes · Clozapine · GLP-1 · Olanzapine

Trial page ClinicalTrials.govUpdated 25 Sept 2024

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.

Version 2Current
11 Oct 2026, 00:04 UTC
Study results updated
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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