Evidence mapPaperPMID 41778920Full record

Trial reportDiabetes care2026

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.

Ashok A Ganeshalingam, Nicolai Uhrenholt, Sidse Arnfred, Peter Gæde, Andreas K Pedersen, Niels Bilenberg, Jan Frystyk

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed, 1 pooled it
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Ashok A GaneshalingamEndocrine Research Unit, Department of Endocrinology, Odense University Hospital, Odense, Denmark.ORCID 0000-0003-2218-5045
Nicolai UhrenholtDepartment of Clinical Research, Faculty of Health Science, University of Southern Denmark, Odense, Denmark.
Sidse ArnfredPsychiatric Research Unit, Copenhagen University Hospital-Psychiatry Region Zealand, Slagelse, Denmark.
Peter GædeDepartment of Internal Medicine, Geriatrics and Neurology, Næstved, Slagelse og Ringsted Sygehuse, Slagelse, Denmark.
Andreas K PedersenOUH, OPEN-Open Patient Data Explorative Network (Odense), Odense, Denmark.
Niels BilenbergDepartment of Clinical Research, Faculty of Health Science, University of Southern Denmark, Odense, Denmark.
Jan FrystykEndocrine Research Unit, Department of Endocrinology, Odense University Hospital, Odense, Denmark.

Funding

Aase og Ejnar Danielsens FondNovo Nordisk Fonden NNF19OC0058155Region SjællandSteno Diabetes Center OdenseSteno Diabetes Center Zealand
6 · The paper itself

Abstract

objectiveTo examine the effects of semaglutide on insulin sensitivity, insulin resistance, and β-cell function and explore whether these changes were mediated by weight loss in overweight or obese individuals with schizophrenia and prediabetes receiving second-generation antipsychotics. RESEARCH DESIGN AND

methodsIn this 30-week, double-blind trial, 154 participants were randomized to semaglutide (n = 77) or placebo (n = 77); 141 (91.5%) completed the study. Baseline and end-of-study assessments included fasting glucose, insulin, C-peptide, HOMA2 of β-cell function, HOMA2 of insulin sensitivity, HOMA of insulin resistance, and body weight.

resultsParticipants (56% women, mean age 38.3 years) provided complete insulin data in 131 cases. 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). 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). 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), with a modest, nonsignificant increase in β-cell function (8.10; P = 0.19).

conclusionsSemaglutide significantly improved insulin sensitivity, reduced insulin resistance, lowered fasting glucose, and promoted substantial weight loss in patients with antipsychotic-induced metabolic disturbances. Weight loss partly mediated the metabolic improvements, while β-cell function remained largely unchanged. These findings support semaglutide as a potential strategy for mitigating metabolic dysfunction in this high-risk population.

Indexed as

Antipsychotic AgentsGlucagon-Like PeptidesInsulin ResistanceInsulin-Secreting CellsObesityPrediabetic StateSchizophreniaAdultBlood GlucoseC-PeptideDouble-Blind MethodFemaleHumansInsulinMaleMiddle AgedAntipsychotic AgentsBlood GlucoseC-PeptideGlucagon-Like PeptidesInsulinSemaglutide

Identifiers

PMID41778920
PMCPMC13094869

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.