Metformin Alleviates Abnormal Glucose Metabolism Induced by Statins in Schizophrenia Patients

NCT07045142 | Recruiting Phase 3

• 1 other identifier: WU202505STA
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 8

Brief Summary

Schizophrenia is a severe mental illness associated with significant morbidity and disability. Patients often experience metabolic side effects from antipsychotic medications, including weight gain and dyslipidemia. Statins, commonly used to manage dyslipidemia, can lower cholesterol levels but may increase the risk of new-onset diabetes. This study aims to investigate how atorvastatin affects glucose metabolism in schizophrenia patients and assess whether metformin can help improve these metabolic issues. The investigators will include 200 patients with dyslipidemia from the Second Xiangya Hospital and other sites, randomly assigning them to receive either atorvastatin with metformin or atorvastatin with placebo over six months. Key goals include evaluating the impact of atorvastatin on insulin resistance and blood glucose levels and determining the effectiveness of metformin in mitigating glucose metabolism abnormalities while managing lipid levels. Understanding these interactions will help improve treatment strategies for schizophrenia patients, potentially lowering their risk of cardiovascular diseases and diabetes and enhancing overall health outcomes.

Conditions

Schizophrenia

Keywords

Schizophrenia; Dyslipidemia; Metformin; Statin

Outcome Measures

Primary Outcomes (3)

• Change from Baseline in Fasting Blood Glucose Concentration

  Baseline, 3rd month, 6th month

• Change from Baseline in Glycated Hemoglobin (HbA1c) Concentration

  Baseline, 3rd month, 6th month

• Oral Glucose Tolerance Test

  The Oral Glucose Tolerance Test (OGTT) requires subjects to undergo an 8-hour fasting period, followed by an initial measurement of fasting blood glucose via a portable glucometer using a finger prick. Subsequently, subjects are instructed to consume a solution containing 75 grams of anhydrous glucose dissolved in 300 milliliters of water. Blood samples are then collected through finger pricking at 1 hour and 2 hours post-ingestion for further analysis of glucose levels.

  Baseline, 3rd month, 6th month

Secondary Outcomes (5)

• Change from Baseline in Fasting insulin Concentration

  Baseline, 3rd month, 6th month

• Homeostasis Model Assessment of Insulin Resistance (HOMA-IR)

  Baseline, 3rd month, 6th month

• Change from Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score

  Baseline, 3rd month, 6th month

• Change from Baseline in Global Assessment of Functioning Scale (GAF) Total Score

  Baseline, 3rd month, 6th month

• Abdominal ultrasound examination.

  baseline, 6 months

Study Arms (2)

Metformin group

ACTIVE COMPARATOR

To explore the impact of metformin on glucose metabolism abnormalities in schizophrenia patients undergoing atorvastatin treatment.

Drug: Atorvastatin; Drug: Metformin

Placebo group

PLACEBO COMPARATOR

To serve as a placebo control for evaluating the effects of atorvastatin treatment on glucose metabolism in schizophrenia patients, isolating the impact of metformin from the effects of atorvastatin.

Drug: Atorvastatin; Drug: Placebo

Interventions

Atorvastatin DRUG

Participants will receive atorvastatin 20 mg daily.

Metformin group; Placebo group

Metformin DRUG

Participants will receive metformin 1000 mg daily.

Metformin group

Placebo DRUG

Participants will receive placebo 1000 mg daily, mimicking the appearance of metformin without containing active ingredients.

Placebo group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged between 18 and 65 years, regardless of gender, and meets the diagnostic criteria for schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5);
• Symptoms and medication regimen stable for more than 3 months, with the allowance of up to two antipsychotic medications in combination (concurrent use of antidepressants, anxiolytics, and mood stabilizers is permitted);
• Temporary use of benzodiazepines is allowed;
• Meets at least one of the following conditions: fasting total cholesterol (TC) ≥ 5.2 mmol/L; fasting triglycerides (TG) ≥ 1.7 mmol/L; fasting low-density lipoprotein cholesterol (LDL-C) ≥ 3.4 mmol/L;
• Two fasting blood glucose (FPG) tests must be \< 6.1 mmol/L (with an interval of 1-4 weeks);
• It is anticipated that there will be no issues related to relocation, transportation difficulties, or access to medical care throughout the study;
• Informed consent must be obtained from the patient and their guardian, and a consent form must be signed.

You may not qualify if:

• Patients with a prior diagnosis of diabetes or complications such as diabetic ketoacidosis;
• Patients with severe gastrointestinal, respiratory, endocrine, hematologic diseases, or metabolic absorption disorders: including but not limited to poorly controlled diabetes, severe acute systemic infections or immunological diseases, ischemic heart disease, cerebrovascular accidents within the past year, history of prolonged QT interval, active hepatitis B virus, chronic active hepatitis C, and malabsorption syndromes;
• Pregnant or nursing women.

Sponsors & Collaborators

• Junshan District Psychiatric Rehabilitation Hospital: collaborator
• The Second People's Hospital of Xiangyin County: collaborator
• The Third Hospital of Changsha County: collaborator
• Xiangshan County Traditional Chinese Medicine Hospital Medical and Health Group Three Hospitals Distric: collaborator
• Central South University: lead
• Zhumadian Second People's Hospital: collaborator
• The Second People's Hospital of Dali Bai Autonomous Prefecture: collaborator
• Yueyang Rehabilitation Hospital: collaborator

Study Sites (8)

Zhumadian Second People's Hospital

Zhumadian, Henan, China

RECRUITING

Mental Health Institute of Second Xiangya Hospital, CSU

Changsha, Hunan, China

RECRUITING

The Third Hospital of Changsha County

Changsha, Hunan, China

RECRUITING

The Second People's Hospital of Xiangyin County

Yueyang, Hunan, 410500, China

RECRUITING

Junshan District Psychiatric Rehabilitation Hospital

Yueyang, Hunan, 414000, China

RECRUITING

Yueyang Rehabilitation Hospital

Yueyang, Hunan, 414022, China

RECRUITING

The Second People's Hospital of Dali Bai Autonomous Prefecture

Dali, Yunnan, China

RECRUITING

Xiangshan County Traditional Chinese Medicine Hospital Medical and Health Group Three Hospitals District

Xiangshan, Zhejiang, 315799, China

RECRUITING

Related Publications (4)

• Sasaki J, Otonari T, Uchida Y, Ikeda Y, Biro S, Kono S; PRAT study investigators. Effects of pravastatin and atorvastatin on HDL cholesterol and glucose metabolism in patients with dyslipidemia and glucose intolerance: the PRAT study. J Atheroscler Thromb. 2013;20(4):368-79. doi: 10.5551/jat.13532. Epub 2012 Dec 15.

  PMID: 23257975 RESULT

• Preiss D, Seshasai SR, Welsh P, Murphy SA, Ho JE, Waters DD, DeMicco DA, Barter P, Cannon CP, Sabatine MS, Braunwald E, Kastelein JJ, de Lemos JA, Blazing MA, Pedersen TR, Tikkanen MJ, Sattar N, Ray KK. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011 Jun 22;305(24):2556-64. doi: 10.1001/jama.2011.860.

  PMID: 21693744 RESULT

• Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJ, Seshasai SR, McMurray JJ, Freeman DJ, Jukema JW, Macfarlane PW, Packard CJ, Stott DJ, Westendorp RG, Shepherd J, Davis BR, Pressel SL, Marchioli R, Marfisi RM, Maggioni AP, Tavazzi L, Tognoni G, Kjekshus J, Pedersen TR, Cook TJ, Gotto AM, Clearfield MB, Downs JR, Nakamura H, Ohashi Y, Mizuno K, Ray KK, Ford I. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010 Feb 27;375(9716):735-42. doi: 10.1016/S0140-6736(09)61965-6. Epub 2010 Feb 16.

  PMID: 20167359 RESULT

• Pillinger T, McCutcheon RA, Vano L, Mizuno Y, Arumuham A, Hindley G, Beck K, Natesan S, Efthimiou O, Cipriani A, Howes OD. Comparative effects of 18 antipsychotics on metabolic function in patients with schizophrenia, predictors of metabolic dysregulation, and association with psychopathology: a systematic review and network meta-analysis. Lancet Psychiatry. 2020 Jan;7(1):64-77. doi: 10.1016/S2215-0366(19)30416-X. Epub 2019 Dec 17.

  PMID: 31860457 RESULT

MeSH Terms

Conditions

Schizophrenia; Dyslipidemias

Interventions

Atorvastatin; Metformin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids; Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Renrong Wu

  Mental Health Institute of Second Xiangya Hospital,CSU

  STUDY CHAIR

Central Study Contacts

Jing Huang

CONTACT

+86 15874290980; jinghuangserena@csu.edu.cn

Xinyi Zhao

CONTACT

+86 17803908545; 852646662@qq.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: We will include 200-400 schizophrenia patients with dyslipidemia from the Second Xiangya Hospital and other sites, randomly assigning them to receive either atorvastatin with metformin or atorvastatin with placebo. Two groups were observed longitudinally for 6 months.

Study Record Dates

• First Submitted: June 22, 2025
• First Posted: July 1, 2025
• Study Start: July 1, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

CN (8)