HISTORI

CompletedPhase 2

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

Lead sponsor

Jan Frystyk

Asset

Semaglutide

GLP-1 agonist

Listed sites

Recruiting sites

Actual enrollment

154

Study population

Obesity / overweight, Prediabetes / glucose intolerance, Psychiatric (schizophrenia / bipolar / depression)

Eligibility highlights

•BMI ≥27

Primary endpoint

•HbA1c, change

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT05193578

Org study IDEudra CT 2020-004374-22

Timeline

Milestones

Study start2022-01-01actual

Study first posted2022-01-18actual

Primary completion2024-03-18actual

Study completion2024-05-01actual

Last update posted2024-07-08actual

Assets

Investigational agents

Semaglutide

Who this study enrolls

Obesity / overweightPrediabetes / glucose intolerancePsychiatric (schizophrenia / bipolar / depression)

Who can enroll

Minimum age18 Years

Maximum age60 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Diagnosed with schizophrenia spectrum disorder (ICD10 codes DF20, DF21 or DF25)

•Age between 18 and 60 years (both included)

•Approved contraception for female participants

•Treated by one of the OPUS clinics and or community psychiatry centers teams and community psychiatry in the Region of Southern Denmark or Zealand

•Antipsychotic SGA treatment for at least 6 months

•Stable co-medication for at least 1 month

•HbA1c between 39-47 mmol/mol (both included). Two measurements with ≥3 month interval are required to confirm prediabetes. The first measurement is identified and obtained from patient journals, the second prior to enrolment

•BMI ≥27 kg/m2. Two weights with ≥3 month interval are required to confirm obesity

•Capable of providing informed oral and written consent

Exclusion criteria

•Diagnosis of diabetes (T1D or T2D) or a HbA1c >47 mmol/mol

•Active malignant disease within the last 5 years

•Pregnancy or breast feeding

•Exceeding high risk consumption limit (>21 / 14 units of alcohol for men / women, respectively) or severe substance abuse

•Unwillingness to allow home visits by a study nurse

•Significant somatic disease: 1) end-stage renal failure (eGFR <15 ml/min); 2) elevated liver function tests (liver transaminases >2 times upper normal limit); 3) history of acute or chronic pancreatitis; 4) heart failure (NYHA class IV) or unstable angina pectoris or myocardial infarction with the last 6 months; 5) uncontrolled hypertension (systolic blood pressure >180 mm Hg, diastolic blood pressure >100 mm Hg)

•Previous treatment with study drug or use of other weight reducing drugs within the last 6 month

•Participation in other drug trials

•Treatment with drugs approved for overt diabetes type 2. (Metformin not included)

•Circumstances that the investigator believes will interfere with the trial

Endpoints (17)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Cardiometabolic biomarkers

Patient-reported / QoL

Weight & body composition

Glycemic / diabetes

Other clinical outcomes

Weight & body composition

4 endpoints

Secondary/protocol endpoint

Weight

Time frame:30 weeks

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Height

Time frame:30 weeks

change from baseline, descriptive

Secondary/protocol endpoint

Chaneges in body mass index (BMI)

Time frame:30 weeks

BMI, change

change from baseline, improvement

Secondary/protocol endpoint

Waist circumference (cm)

Time frame:30 weeks

Waist circumference, change

change from baseline, improvement

Glycemic / diabetes

2 endpoints

Primary/protocol endpoint

HbA1c (mmol/mol)

Time frame:30 weeks

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Secondary/protocol endpoint

Glycemic status (blood sampling)

Time frame:30 weeks

HOMA-IR (insulin sensitivity)

change from baseline, improvement

Cardiometabolic biomarkers

5 endpoints

Secondary/protocol endpoint

Plasma triglyceride

Time frame:30 weeks

Triglycerides, change

change from baseline, improvement

LOINC 2571-8

Secondary/protocol endpoint

Cholesterol concentrations

Time frame:30 weeks

Total cholesterol, change

change from baseline, improvement

LOINC 2093-3

Secondary/protocol endpoint

Absolute change in systolic and diastolic blood pressure (mmHg)

Time frame:30 weeks

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Cardiovascular risk markers

Time frame:30 Weeks

descriptive

Secondary/protocol endpoint/low confidence

Pro-atherosclerotic changes

Time frame:30 Weeks

change from baseline, improvement

Patient-reported / QoL

5 endpoints

Secondary/protocol endpoint

Impact of Weight on Quality of Life-Lite

Time frame:30 Weeks

IWQOL-Lite total

change from baseline, improvement

Secondary/protocol endpoint

Short Form Survey version 2 (SF-36v2)

Time frame:30 Weeks

SF-36 total

change from baseline, improvement

Secondary/protocol endpoint

Medication Adherence Rating Scale

Time frame:30 Weeks

change from baseline, improvement

Secondary/protocol endpoint

The Simple Physical Activity Questionnaire

Time frame:30 Weeks

descriptive

Secondary/protocol endpoint

EQ-5D-3L

Time frame:30 Weeks

EQ-5D index

change from baseline, improvement

Other clinical outcomes

1 endpoint

Secondary/protocol endpoint

Positive and Negative Symptom Scale 6

Time frame:30 Weeks

change from baseline, improvement

Publications (3)

Bibliography

Records linked to this trial through ClinicalTrials.gov references, PubMed NCT search, and curated study seeds. 'Canonical' marks design/result papers; others are registry references or candidates.

Registry references + supporting bibliography

Cardiac autonomic neuropathy in patients with SGA-treated schizophrenia: a randomized controlled trial of 30 weeks' treatment with semaglutide.
Cardiovascular diabetology. Endocrinology reports2026 Jan 20PMID41555458doi:10.1186/s40842-025-00258-0via pubmed nct search
Semaglutide Treatment of Antipsychotic-Treated Patients With Schizophrenia, Prediabetes, and Obesity: The HISTORI Randomized Clinical Trial.
JAMA psychiatry2025 Nov 1PMID40900607doi:10.1001/jamapsychiatry.2025.2332via clinicaltrials gov reference derived + pubmed nct search
Home-based Intervention with Semaglutide Treatment of Neuroleptic-Related Prediabetes (HISTORI): protocol describing a prospective, randomised, placebo controlled and double-blinded multicentre trial.
BMJ open2024 Mar 18PMID38503415doi:10.1136/bmjopen-2023-077173via clinicaltrials gov reference derived + pubmed nct search

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateJuly 6, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 6, 2026 snapshot.