Metformin to prevent statin-related blood sugar changes in people with schizophrenia

Metformin Alleviates Abnormal Glucose Metabolism Induced by Statins in Schizophrenia Patients: A Randomized, Double-Blind, Placebo-Controlled Multicenter Clinical Study

This project will test whether adding metformin to atorvastatin helps prevent increases in blood sugar in adults with schizophrenia who have high cholesterol or triglycerides.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 400 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Central South University (Academic / other)
• Locations: 8 sites (Zhumadian, Henan and 7 other locations)
• Trial ID: NCT07045142 on ClinicalTrials.gov

What this trial studies

In this randomized, double-blind Phase 3 trial, about 200 adults with schizophrenia and dyslipidemia will be assigned to receive atorvastatin plus metformin or atorvastatin plus placebo for six months. Participants must be clinically stable on antipsychotic medication and have normal fasting glucose at entry. Primary outcomes include changes in insulin resistance and fasting blood glucose, with secondary outcomes tracking lipid control and safety. The trial is being conducted at multiple hospitals affiliated with Central South University in China.

Who should consider this trial

Good fit: Adults aged 18–65 with DSM-5 schizophrenia who are clinically stable on antipsychotic treatment and have dyslipidemia but normal fasting glucose are ideal candidates.

Not a fit: People who already have diabetes, have unstable psychiatric symptoms, or cannot attend regular clinic visits are unlikely to benefit or be eligible.

Why it matters

Potential benefit: If successful, adding metformin could allow patients to get the cholesterol-lowering benefits of statins while reducing the risk of developing higher blood sugar or diabetes.

How similar studies have performed: Metformin has been shown to improve antipsychotic-associated weight gain and insulin resistance and statins have been linked to a small increased diabetes risk in general populations, but randomized data specifically testing metformin to offset statin-related glucose changes in schizophrenia are limited.

Eligibility criteria

Inclusion criteria:

1. 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);
2. 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);
3. Temporary use of benzodiazepines is allowed;
4. 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;
5. Two fasting blood glucose (FPG) tests must be \< 6.1 mmol/L (with an interval of 1-4 weeks);
6. It is anticipated that there will be no issues related to relocation, transportation difficulties, or access to medical care throughout the study;
7. Informed consent must be obtained from the patient and their guardian, and a consent form must be signed.

Exclusion criteria:

1. Patients with a prior diagnosis of diabetes or complications such as diabetic ketoacidosis;
2. Patients with liver or kidney dysfunction, indicated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), or gamma-glutamyl transferase (GGT) levels exceeding twice the normal limits, and/or creatinine levels exceeding 1.2 times the upper limit of the reference range or greater than 2 mg/dL, or deemed by the investigator to have liver and/or kidney impairment that warrants exclusion from the study;
3. 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;
4. Clinically significant abnormal ECG findings at screening that the investigator deems unsuitable for inclusion, such as male QTc interval \> 470 ms, female QTc interval \> 480 ms;
5. Pregnant or nursing women.

Where this trial is running

Zhumadian, Henan and 7 other locations

• 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, China (Recruiting)
• Junshan District Psychiatric Rehabilitation Hospital — Yueyang, Hunan, China (Recruiting)
• Yueyang Rehabilitation Hospital — Yueyang, Hunan, 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, China (Recruiting)

Study contacts

• Study coordinator: Jing Huang

Conditions Schizophrenia; Dyslipidemia; Metformin; Statin