Semaglutide Effects on Insulin Sensitivity and β-Cell Function in Patients With Schizophrenia, Prediabetes, and Obesity Treated With Second-Generation Antipsychotics: Findings From the HISTORI Trial, a 30-Week Randomized, Placebo-Controlled Trial With Semaglutide 1.0 mg Weekly.

Ganeshalingam AA, Uhrenholt N, Arnfred S, Gæde P, Pedersen AK, Bilenberg N, Frystyk J

Diabetes care1 May 2026Cited by 2 (Europe PMC)

PMID41778920PMCIDPMC13094869DOI10.2337/dc25-2041PepBankPUB-41778920

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 study9

9 results from studies that gave the peptide. 9 results from people.

01HumanRandomized controlled trialEfficacy outcome
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, semaglutide reduced fasting glucose versus placebo (-0.87 mmol/L).
In plain wordsIn people with schizophrenia, prediabetes and obesity, semaglutide lowered fasting blood sugar more than placebo.
Peptide
Semaglutide
Outcome
DecreaseFasting glucose
Study
n = 131
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Measurements
fasting glucose difference
−0.87 mmol/L
semaglutide minus placebo
Source sentences
Summary
Compared with placebo, semaglutide significantly reduced fasting glucose (-0.87 mmol/L [95% CI -1.15, -0.59]; P < 0.001)
1 context sentence(design, population, supporting numbers)
Summary · context
In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study.
Report a problemFND-4177892001
02HumanRandomized controlled trialEfficacy outcome
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, semaglutide improved insulin sensitivity versus placebo.
In plain wordsIn people with schizophrenia, prediabetes and obesity, semaglutide improved insulin sensitivity more than placebo.
Peptide
Semaglutide
Outcome
IncreaseInsulin sensitivity (HOMA2 of insulin sensitivity)
Study
n = 131
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Source sentences
Summary
Compared with placebo, semaglutide significantly reduced fasting glucose (-0.87 mmol/L [95% CI -1.15, -0.59]; P < 0.001), improved insulin sensitivity (8.60 [5.82, 13.65]; P = 0.001)
1 context sentence(design, population, supporting numbers)
Summary · context
In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study.
Report a problemFND-4177892002
03HumanRandomized controlled trialEfficacy outcome
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, semaglutide lowered insulin resistance versus placebo.
In plain wordsIn people with schizophrenia, prediabetes and obesity, semaglutide lowered insulin resistance more than placebo.
Peptide
Semaglutide
Outcome
DecreaseInsulin resistance (HOMA of insulin resistance)
Study
n = 131
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Measurements
insulin resistance difference
−0.69
semaglutide minus placebo
Source sentences
Summary
Compared with placebo, semaglutide significantly reduced fasting glucose (-0.87 mmol/L [95% CI -1.15, -0.59]; P < 0.001), improved insulin sensitivity (8.60 [5.82, 13.65]; P = 0.001), and lowered insulin resistance (-0.69 [-1.00, -0.20]; P = 0.006).
Report a problemFND-4177892003
04HumanRandomized controlled trialEfficacy outcome
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, semaglutide showed a nonsignificant trend toward reduced fasting insulin (-52.3 pmol/L).
In plain wordsIn people with schizophrenia, prediabetes and obesity, semaglutide did not clearly change fasting insulin compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeFasting insulin
Study
n = 131
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Measurements
fasting insulin difference
−52.3 pmol/L
semaglutide minus placebo
Source sentences
Summary
Nonsignificant trends were observed toward reduced fasting insulin (-52.3 pmol/L; P = 0.11)
1 context sentence(design, population, supporting numbers)
Summary · context
In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study.
Report a problemFND-4177892004
05HumanRandomized controlled trialEfficacy outcome
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, semaglutide showed a nonsignificant trend toward reduced C-peptide (-182.9 pmol/L).
In plain wordsIn people with schizophrenia, prediabetes and obesity, semaglutide did not clearly change C-peptide compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeC-peptide
Study
n = 131
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Measurements
C-peptide difference
−182.9 pmol/L
semaglutide minus placebo
Source sentences
Summary
Nonsignificant trends were observed toward reduced fasting insulin (-52.3 pmol/L; P = 0.11) and C-peptide (-182.9 pmol/L; P = 0.096)
1 context sentence(design, population, supporting numbers)
Summary · context
In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study.
Report a problemFND-4177892005
06HumanRandomized controlled trialEfficacy outcome
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, semaglutide produced a modest, nonsignificant increase in beta-cell function.
In plain wordsIn people with schizophrenia, prediabetes and obesity, semaglutide did not clearly change beta-cell function compared with placebo.
Peptide
Semaglutide
Outcome
No significant changeBeta-cell function (HOMA2 of beta-cell function)
Study
n = 131
Comparator
Placebo
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Source sentences
Summary
with a modest, nonsignificant increase in β-cell function (8.10; P = 0.19).
1 context sentence(design, population, supporting numbers)
Summary · context
In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study.
Report a problemFND-4177892006
07HumanRandomized controlled trialEfficacy outcome
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, mean weight loss with semaglutide was 9.2 kg.
In plain wordsIn people with schizophrenia, prediabetes and obesity, semaglutide was linked to a mean weight loss of 9.2 kg.
Peptide
Semaglutide
Outcome
DecreaseWeight loss
Study
n: not reported in source
Outcome group
Body weight · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Measurements
mean weight loss
9.2 kg
semaglutide
Source sentences
Summary
Mean weight loss was 9.2 kg and mediated improvements in insulin sensitivity (estimate 7.82; P = 0.01) and insulin resistance (estimate -0.75; P = 0.01).
1 context sentence(design, population, supporting numbers)
Summary · context
In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study.
Report a problemFND-4177892007
08HumanRandomized controlled trialMechanism
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, weight loss mediated the semaglutide improvement in insulin sensitivity (estimate 7.82).
In plain wordsIn people with schizophrenia, prediabetes and obesity, part of the semaglutide gain in insulin sensitivity was explained by weight loss.
Peptide
Semaglutide
Outcome
IncreaseMediation of insulin sensitivity improvement by weight loss
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Measurements
mediation estimate
7.82
insulin sensitivity
Source sentences
Summary
mediated improvements in insulin sensitivity (estimate 7.82; P = 0.01)
1 context sentence(design, population, supporting numbers)
Summary · context
In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study.
Report a problemFND-4177892008
09HumanRandomized controlled trialMechanism
In people with schizophrenia, prediabetes and obesity on second-generation antipsychotics, weight loss mediated the semaglutide reduction in insulin resistance (estimate -0.75).
In plain wordsIn people with schizophrenia, prediabetes and obesity, part of the semaglutide drop in insulin resistance was explained by weight loss.
Peptide
Semaglutide
Outcome
DecreaseMediation of insulin resistance reduction by weight loss
Study
n: not reported in source
Outcome group
Glycemic control · Metabolic and weight
Studied dose
1.0 mg weekly · 30 weeksAs given in this study (human).
Measurements
mediation estimate
−0.75
insulin resistance
Source sentences
Summary
and insulin resistance (estimate -0.75; P = 0.01).
1 context sentence(design, population, supporting numbers)
Summary · context
In this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study.
Report a problemFND-4177892009

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.

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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