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Trial · Interventional

Status unknownPhase 4Registry data

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

Overview

Status
Status unknown
Phase
Phase 4
Enrollment
104 participants (estimated)
Sponsor
Anders Fink-Jensen, MD, DMSci · Other
Design
Randomized · Triple masking
Countries
1 country

Denmark

Start
1 Sept 2021
Primary completion
1 Mar 2026 (estimated)
Completion
1 Aug 2026 (estimated)
First posted
19 May 2021
Last update posted
25 Sept 2024
Conditions
Metabolic Disturbance · Schizophrenia · Type 2 Diabetes · Clozapine · GLP-1 · Olanzapine

Timeline

1 trial

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2021202220232024202520262027
  1. Ph 4

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

    NCT04892199

    1 Sept 2021 to est. 1 Aug 2026

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

Background and objective: Clozapine and olanzapine are some of the most effective antipsychotic drugs, but unfortunately, both drugs induce weight gain and conveys a high degree of metabolic disturbances. The antipsychotic-induced side-effects cause a major clinical problem among patients diagnosed with schizophrenia receiving antipsychotic treatment. Limited effects have been demonstrated for counteracting the side-effects by the switch of antipsychotic therapy, non-pharmacological/behavioural interventions or adjunct pharmacological treatments. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA,) is approved for the treatment of type 2 diabetes worldwide. The objective of the study is to investigate effects of semaglutide once-weekly vs. semaglutide placebo once-weekly on the metabolic state in prediabetic or diabetic patients with schizophrenia, who have initiated treatment with clozapine or olanzapine. Methods and analysis: Trial design, intervention and participants: The study is a 26-week, double-blinded, randomized, parallel-group, placebo-controlled, good clinical practice (GCP)-monitored, clinical trial. 104 prediabetic or diabetic patients diagnosed with a schizophrenia, age 18 years and 65 years, who have initiated of clozapine- or olanzapine-treatment within 5 years will be included in the study. The patients will be randomized to receive blinded treatment in one of the two study arms; semaglutide once-weekly vs. semaglutide placebo. All participants who complete the 26 weeks of intervention, will be invited for a follow up visit 1.5 yeras after study completion. The primary endpoint is the change from baseline in glycated haemoglobin A1c (HbA1c). Secondary endpoints include change in body weight, hip and waist circumference, vitals, and plasma levels of insulin, glucose, C-peptid, insulin sensitivity, beta cell function, glucagon, liver function, lipid profile, incretin hormones, lipid profile, bone makers, body composition, bone density and proteomic analyses. Additional endpoints include alcohol, tobacco and drug use, food preferences, psychopathology, activity and quality of life.

Interventions

  • Semaglutide, 1.34 mg/mLDrug
  • Semaglutide-placeboDrug

Arms2

  • Active comparator

    Semaglutide injection once-weekly

  • Placebo comparator

    Semaglutide-Placebo injection once-weekly

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. The primary endpoint is the change from baseline in glycated haemoglobin A1c (HbA1c).

    Time frame · 26 weeks

Secondary outcomes(20)
  1. Body weight (Kg)

    Time frame · 26 weeks

  2. Hip and Waist circumference (Cm)

    Time frame · 26 weeks

  3. Incretin hormones (Blood sampling)

    Time frame · 26 weeks

    Registry description

    GLP-1, GLP-2 and GIP

  4. Bone Markers (Blood sampling)

    Time frame · 26 weeks

    Registry description

    Calcitonin, Vit-D, Ca, Phosphate, Mg, PTH, PINP, CTX, OC

  5. Lipid Profile (Blood sampling)

    Time frame · 26 weeks

    Registry description

    LDL, HDL, triglycerider, total kolesterol,

  6. Hormones (blood sampling)

    Time frame · 26 weeks

    Registry description

    Insulin, glucagon and C-peptide

  7. Visceral fat

    Time frame · 26 weeks

    Registry description

    DXA scanning

  8. Android to Gynoid fat ratio

    Time frame · 26 weeks

    Registry description

    DXA scanning

  9. Total body fat

    Time frame · 26 weeks

    Registry description

    DXA scanning

  10. Bone density

    Time frame · 26 weeks

    Registry description

    DXA scanning

  11. Psychopathology

    Time frame · 26 weeks

    Registry description

    PANSS-6 interview

  12. Registration of body movements/level of activity with a sensor

    Time frame · 26 weeks

    Registry description

    Activity measurements (approximate for sleep, inactivity, energy expenditure and steps taken by the patient) will be collected continuously by the use of a wearable activity device worn by the patient for 1 week from inclusion day and 1 week at the end of the study

  13. Reward value of sweet and fatty candy

    Time frame · 26 weeks

    Registry description

    Clicker test

  14. Alcohol use

    Time frame · 26 weeks

    Registry description

    Questionnaires: AUDIT

  15. Tobacco use

    Time frame · 26 weeks

    Registry description

    Questionnaires: FNTD

  16. Drug use

    Time frame · 26 weeks

    Registry description

    Questionnaires: DUDIT

  17. Schizophrenia quality of life scale

    Time frame · 26 weeks

    Registry description

    Questionnaire: SQLS

  18. Psychosocial disability

    Time frame · 26 weeks

    Registry description

    Rating GAPD

  19. Liver function (blood sampling)

    Time frame · 26 weeks

    Registry description

    ALT, ALP, AST, trombocytes and bilirubin

  20. Proteomic analyses (Blood sampling)

    Time frame · 26 weeks

    Registry description

    Inflammatory biomarkers and cytokines: IFN-γ, TNF-α, IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, MDA, plasma antioxidants uric acid and, vitaminC

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

No results are posted for this trial.

A trial that is still running, or that stopped early, may post results later.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

Studies with results

1 study on this page

Indexing hint: Randomized controlled trial · 2026

11 results

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

Sass et al. 2026JAMA psychiatrycited by 13

PMID 41335431DOI 10.1001/jamapsychiatry.2025.3639PUB-41335431

Full text at the publisher11 results

Indexing hint: Clinical trial · 2023

Effect of the GLP-1 receptor agonist semaglutide on metabolic disturbances in clozapine-treated or olanzapine-treated patients with a schizophrenia spectrum disorder: study protocol of a placebo-controlled, randomised clinical trial (SemaPsychiatry).

Sass et al. 2023BMJ opencited by 33

PMID 36720576PMC9890830DOI 10.1136/bmjopen-2022-068652PUB-36720576

Free to read · publisher termsCC BY-NC
Read at source

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: 1. Informed oral and written consent 2. Diagnosed with schizophrenia according to the criteria of ICD-10 (International Classification of Diseases, World Health Organization (WHO)) or the DSM-V (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, the American Psychiatric Association) 3. Initiating current treatment with clozapine or olanzapine within 60 months (not PRN ordinations) 4. Age 18 years to 65 years (both included) 5. Body mass index (BMI) ≥25 kg/m2 6. Diagnosed with prediabetes or type 2 diabetes, after initiation of current treatment with clozapine- or olanzapine, with the following plasma levels: Prediabetes: HbA1c 35-47 mmol/mol or fasting plasma glucose (FPG) 5.6-6.9 mM or 2-h during 75 mg OGGT 7.8-11.0 mM. The test result has to be confirmed on a different day. Type 2 diabetes: HbA1c 48-57 mmol/mol or fasting plasma glucose (FPG) 6.9-9.9 mM or 2h OGTT \> 11 mM (although FPG and HbA1c might still be under the diagnostic range). The test result has to be confirmed on a different day. Exclusion Criteria: 1. Acute worsening of psychosis based on a clinical evaluation (score of 6 or 7 on the CGI-S scale) 2. Coercive measures 3. Females of child-bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant. 4. Women who are not willing to use adequate contraceptive during the full length of the study 5. Patients treated with corticosteroids or other hormone therapy (except oestrogens) 6. Any active substance abuse or dependence for the past six months (except for nicotine) 7. Impaired hepatic function (plasma liver transaminases \>3 times upper normal limit) 8. Impaired renal function (serum creatinine \>150 μmol/l and/or macroalbuminuria) 9. Impaired pancreatic function (acute or chronic pancreatitis and/or plasma amylase \>2 times upper normal limit) 10. Cardiac problems defined as decompensated heart failure (NYHA class III/IV), unstable angina pectoris and/or myocardial infarction within the last 12 months 11. Hypertension with systolic blood pressure \>180 mmHg or diastolic blood pressure \>100 mmHg 12. Any condition that the investigator feels would interfere with trial participation 13. Receiving any experimental or pre-marketing drug within the last 3 months 14. Use of weight-lowering pharmacotherapy within the preceding 3 month 15. Known type 1 diabetes 16. Suicidal behavior as judged by the investigator and based on clinical evaluation. At all contact with patient attendance possible suicidality will be evaluated according to the guidelines. If the patient is evaluated as suicidal, the person will be excluded from the study and evaluated by a senior consultant in psychiatry, who will take further action. 17. Plasma HbA1c \> 57 mmol/mol (tested twice) in which case the patient will be excluded from the study and transferred to general practitioner or hospital for diabetic treatment. No diabetic medication is allowed except for the trial medicin. 18. Any known contraindication towards the treatment with semaglutide.

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