Efficacy of Metformin in Preventing Diabetes in China

Study Overview
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Brief Summary
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A multicentred, randomized, open study to evaluate the efficacy of metformin in preventing Diabetes.

Detailed Description
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The increasing prevalence of prediabetes had been documented in the recent national surveillance in China. Prediabetes is an important risk factor for developing overt Diabetes and macro/micro vascular diseases. Pharmaceutical medications such as metformin had been proved effective in preventing Diabetes. Local studies are in need to guide the clinicians in their daily practice to prevent Diabetes in China. Therefore, China Diabetes Prevention Program（China DPP）is designed and conducted to compare the efficacy of metformin combined with lifestyle intervention versus lifestyle intervention alone in preventing Diabetes.

Official Title
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A Multicentre, Open-labelled, Randomized, Controlled Study to Evaluate the Efficacy of Metformin in Preventing Diabetes in China.

Conditions
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PreDiabetes

Intervention / Treatment
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* Drug: metformin
* Other: Standard lifestyle intervention


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Diagnosis of IGR before the randomization based on the 1999 WHO diagnostic and classification criteria. Age: 18 ≤age≤70 years old. Not on a treatment of anti-diabetic agents, including Chinese traditional herbs lowering blood glucose for at least 6 months before screening. Male or non-pregnant, non-breastfeeding females, females without birthing plan in next three years. Body mass index (BMI) ：21 kg/m2 ≤BMI<32 kg/m2. Written informed consent given before any trial-related activities are carried out. Main exclusion Criteria: Administration with medications for pre-existed diseases affect glucose metabolism (except thiazide diuretics when its daily dose≤12.5mg). Administration with anti-obesity agents (including Chinese traditional medicine) within 6 months of enrolment and during intervention. Administration with three or more than three types antihypertensive drugs. Diabetes patients (subjects with prior history of gestational Diabetes will not be excluded). Have any of the following cardiovascular conditions within 3 months prior to the screening visit: acute myocardial infarction, congestive heart failure defined as New York Heart Association class III/IV or left ventricular ejection fraction ≤40%,) or cerebrovascular accident. Persistent uncontrolled hypertension (systolic blood pressure ≥160mmHg, or diastolic blood pressure ≥100 mmHg). Impaired liver function, have obvious clinical signs or symptoms of liver disease, acute or chronic hepatitis, ALT or AST levels ≥3 times the upper limit of the reference range at the screening visit. Renal dysfunction (eGFR<45ml/min）. Patients ventilated by ventilator. Hypersensitivity to metformin or to any of the excipients such as povidone K 30, magnesium stearate and hypromellose. Disease which may cause tissue hypoxia (especially acute disease, or worsening of chronic respiratory disease). Acute alcohol intoxication, alcoholism. Severe chronic gastrointestinal disease. Severe psychiatric illness. Cancer requiring treatment in past 5 years. Uncontrolled thyroid diseases. Women who are pregnant or breastfeeding . Participation in another clinical trial within the past 30 days . Other significant disease that in the Investigator's opinion would exclude the subject from the trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: metformin plus standard lifestyle intervention<br>Metformin starting dose is 850mg/d, it will be titrated to 850mg twice daily after 2 weeks and maintained until the last subject completes 2 years' intervention. | Drug: metformin<br>* Metformin tablets will be administrated in the experimental arm.<br>* Other names: Glucophage immediate release formulation;|
| Other: Standard lifestyle intervention<br>Standard lifestyle advice will be united for all subjects by providing special booklet. | Other: Standard lifestyle intervention<br>* Standard lifestyle advice will be united for all subjects by providing special booklet. All participants will receive 20-30 minutes individual or group session with assigned nurse addressing the harm of prediabetes and the importance of a healthy lifestyle for preventing Diabetes. The amount of energy intake of the participants will be calculated based on the ideal body weight and physical activity levels. The sample recipe will be explained by the nurse and provided in the diet instruction. Moderate intensity physical activity (150 minutes per week) is recommended. Smoking cessation is encouraged for the smoker. Excessive alcohol intake is encouraged to avoid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of newly diagnosed diabetes |  | The primary outcome will be evaluated when the last subject completes 2 years' intervention. |