Semaglutide Treatment of Antipsychotic-Treated Patients With Schizophrenia, Prediabetes, and Obesity: The HISTORI Randomized Clinical Trial.

Ganeshalingam AA, Uhrenholt N, Arnfred S, Gæde P, Düring S, Stenager EN, Bünger N, Pedersen AK, Bilenberg N, Frystyk J

JAMA psychiatry1 Nov 2025Cited by 35 (Europe PMC)

PMID40900607PMCIDPMC12409653DOI10.1001/jamapsychiatry.2025.2332PepBankPUB-40900607

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 study12

12 results from studies that gave the peptide. 12 results from people.

01HumanRandomized controlled trialEfficacy outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, semaglutide reduced HbA1c by 0.46% of total hemoglobin versus placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, semaglutide lowered blood sugar (HbA1c) more than placebo.
Peptide
Semaglutide
Outcome
DecreaseHbA1c change
Study
n = 154
Comparator
Placebo
Analysis
Primary
Outcome group
Glycemic control · Metabolic and weight
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Measurements
HbA1c change
−0.46 % of total hemoglobin
semaglutide
Source sentences
Summary
Semaglutide reduced HbA1c by 0.46% of total hemoglobin (95% CI, -0.56% to -0.36%)
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060701
02HumanRandomized controlled trialEfficacy outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, semaglutide reduced body weight by 9.21 kg versus placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, semaglutide lowered body weight more than placebo.
Peptide
Semaglutide
Outcome
DecreaseBody weight change
Study
n = 154
Comparator
Placebo
Analysis
Secondary
Outcome group
Body weight · Metabolic and weight
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Body weight change
−9.21 kg
semaglutide
Source sentences
Summary
body weight by 9.21 kg (95% CI, -11.68 to -6.75).
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060702
03HumanRandomized controlled trialEfficacy outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, semaglutide improved physical quality of life by 3.75 points on the SF-36v2 versus placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, semaglutide improved physical quality of life more than placebo.
Peptide
Semaglutide
Outcome
IncreasePhysical quality of life (SF-36v2)
Study
n = 154
Comparator
Placebo
Analysis
Secondary
Outcome group
Exercise and physical function · Mental health and mood
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Physical QoL change
3.75 points
semaglutide
Source sentences
Summary
semaglutide improved physical QoL by 3.75 points on the SF-36v2 (95% CI, 1.52-5.98; P = .001)
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060706
04HumanRandomized controlled trialEfficacy outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, semaglutide had no significant effect on mental quality of life scores versus placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, semaglutide did not change mental quality of life scores compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeMental quality of life
Study
n = 154
Comparator
Placebo
Analysis
Secondary
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
but had no significant effect on mental QoL scores or PANSS-6 score.
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060707
05HumanRandomized controlled trialEfficacy outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, semaglutide had no significant effect on the PANSS-6 symptom score versus placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, semaglutide did not change schizophrenia symptom scores compared with placebo.
Peptide
Semaglutide
Outcome
No significant changePANSS-6 score
Study
n = 154
Comparator
Placebo
Analysis
Secondary
Outcome group
Anxiety and mood · Mental health and mood
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
but had no significant effect on mental QoL scores or PANSS-6 score.
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060708
06HumanRandomized controlled trialEfficacy outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, more patients reached HbA1c below 5.7% with semaglutide (81%) than with placebo (19%).
In plain wordsIn adults with schizophrenia, prediabetes and overweight, far more people on semaglutide than on placebo reached a normal blood sugar level (HbA1c).
Peptide
Semaglutide
Outcome
IncreaseHbA1c below 5.7% of total hemoglobin
Study
n = 154
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Proportion with HbA1c below 5.7%
81%
semaglutide
Proportion with HbA1c below 5.7%
19%
placebo
Source sentences
Summary
An HbA1c less than 5.7% of total hemoglobin was achieved in 81% vs 19% of patients treated with semaglutide and placebo, respectively (P < .001)
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060703
07HumanRandomized controlled trialEfficacy outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, semaglutide improved high-density cholesterol by 10.81 mg/dL versus placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, semaglutide raised HDL (good) cholesterol more than placebo.
Peptide
Semaglutide
Outcome
IncreaseHigh-density cholesterol change
Study
n = 154
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Measurements
HDL cholesterol change
10.81 mg/dL
semaglutide
Source sentences
Summary
improvements in high-density cholesterol by 10.81 mg/dL (95% CI, 2.70-18.53; P = .007)
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060704
08HumanRandomized controlled trialEfficacy outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, semaglutide lowered triglycerides by 29.20 mg/dL versus placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, semaglutide lowered triglycerides more than placebo.
Peptide
Semaglutide
Outcome
DecreaseTriglycerides change
Study
n = 154
Comparator
Placebo
Outcome group
Lipids · Metabolic and weight
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Triglycerides change
−29.2 mg/dL
semaglutide
Source sentences
Summary
triglycerides by -29.20 mg/dL (95% CI, -55.75 to 2.65; P = .03)
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060705
09HumanRandomized controlled trialSafety outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, gastrointestinal symptoms were more frequent with semaglutide than with placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, stomach and bowel symptoms were more common with semaglutide than with placebo.
Peptide
Semaglutide
Outcome
IncreaseGastrointestinal symptoms
Study
n = 154
Comparator
Placebo
Outcome group
Gastrointestinal adverse events · Gastrointestinal
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
Gastrointestinal symptoms were more frequent in semaglutide-treated patients.
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060709
10HumanRandomized controlled trialSafety outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, a few semaglutide-treated patients were hospitalized more frequently than the placebo group.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, a few people on semaglutide were in hospital more often than people on placebo.
Peptide
Semaglutide
Outcome
IncreaseHospitalizations
Study
n = 154
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
A few semaglutide-treated patients were hospitalized more frequently than observed in the placebo-treated group
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060710
11HumanRandomized controlled trialSafety outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, the number of serious adverse effects did not differ between semaglutide and placebo.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, serious side effects were not more common with semaglutide than with placebo.
Peptide
Semaglutide
Outcome
No significant changeSerious adverse effects
Study
n = 154
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Source sentences
Summary
but the number of serious adverse effects did not differ between groups.
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060711
12HumanRandomized controlled trialSafety outcome
In antipsychotic-treated adults with schizophrenia, prediabetes and overweight or obesity, 74 of 77 patients (96%) on semaglutide and 67 of 77 (87%) on placebo completed the trial.
In plain wordsIn adults with schizophrenia, prediabetes and overweight, 96% of people on semaglutide and 87% on placebo finished the trial; no test is reported.
Peptide
Semaglutide
Outcome
IncreaseTrial completion
Study
n = 154
Comparator
Placebo
Outcome group
Adverse events · Whole body
Studied dose
up to 1.0 mg/week · subcutaneous · 30 weeksAs given in this study (human).
Measurements
Completed trial
96%
semaglutide
Completed trial
87%
placebo
Source sentences
Summary
Of 154 randomized patients, 141 (91.5%) completed the trial-74 of 77 patients randomized to semaglutide (96%) and 67 of 77 randomized to placebo (87%).
2 context sentences(design, population, supporting numbers)
Summary · context
SGA-treated patients with schizophrenia, prediabetes, and overweight or obesity were randomized to semaglutide or placebo.
Summary · context
Once-weekly subcutaneous semaglutide or placebo for 30 weeks; semaglutide was titrated up to 1.0 mg/week over 8 weeks.
Report a problemFND-4090060712

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 2NCT05193578

Home-based Intervention With Semaglutide Treatment Of Neuroleptica-Related Prediabetes

Jan Frystykn = 1541 Jan 2022 to 1 May 2024

Schizophrenia · Prediabetic State

Trial page ClinicalTrials.govUpdated 8 Jul 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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