Patients with schizophrenia on second-generation antipsychotics have a high burden of metabolic syndrome and elevated cardiovascular risk, with few effective treatment options. This multicentre, double-blind, placebo-controlled randomised trial evaluates whether adjunctive oral semaglutide 3 mg once daily, added to treatment as usual, reduces 10-year cardiovascular risk (QRISK3) and improves insulin resistance, lipids, weight and metabolic biomarkers over 24 weeks compared with placebo, while confirming psychiatric safety and tolerability.
Clinically diagnosed schizophrenia (ICD-11) on a second-generation antipsychotic (SGA) for more than 6 months.
Metabolic syndrome per NCEP ATP III definition.
Aged above 25 years, any gender.
Patient / Legally Authorised Representative (LAR) provides voluntary written informed consent.
● On clozapine, aripiprazole, or a combination of SGAs.
Any contraindication to semaglutide.
Comorbid severe psychiatric, medical or neurological disorder.
History of organicity or significant head injury.
Parallel
Semaglutide + TAU
DrugSemaglutide - oral tablet 3 mg once daily in the morning (titrated up from a low starting dose over 5 days), added to ongoing second-generation antipsychotic (TAU), for 24 weeks.
Placebo + TAU
DrugPlacebo - matching oral tablet once daily in the morning, added to ongoing second-generation antipsychotic (TAU), for 24 weeks
Change in QRISK3 (QResearch Cardiovascular Risk Prediction Algorithm Version 3),10-year cardiovascular risk score
QRISK3 is a cardiovascular risk prediction tool that calculates the 10-year absolute risk of developing cardiovascular disease (heart attack or stroke). The scale produces a percentage score ranging from 0% to 100%, where 0% represents minimum cardiovascular risk and 100% represents maximum theoretical risk. Risk stratification is typically classified as: \<5% = low risk, 5-10% = intermediate risk, 10-20% = high risk, and \>20% = very high risk. A score of \>20% (or approaching 100%) represents the worst clinical situation, indicating substantially elevated 10-year cardiovascular disease risk requiring intensive preventive interventions, including lifestyle modification and pharmacological treatment (statins, antihypertensives). QRISK3 incorporates clinical variables (age, blood pressure, cholesterol), demographic factors, and comorbidities to stratify risk and guide evidence-based prevention strategies in primary care settings.
Change in LDL/HDL ratio
Change from baseline in lipid ratio from fasting lipid profile
Change in insulin resistance (HOMA-IR)
Change in HOMA-IR from fasting glucose and serum insulin
Change in high-sensitivity CRP (hs-CRP)
Change in hs-CRP measured by ELISA
Change Waist circumference
Anthropometric change from baseline
Click on the lead sponsor to view all of their trials.
All India Institute of Medical Sciences, Bhubaneswar
Lead sponsor
Indian Council of Medical Research
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
