Impacts of PIO/MET Following Short-term Intensive Insulin Treatment in Newly Diagnosed Type 2 Diabetes

Sun Yat-sen University

Status and phase: Unknown; Phase 4

Conditions: Type 2 Diabetes Mellitus

Treatments: Drug: Pioglitazone + Metformin; Drug: Placebo Oral Tablet

Study type: Interventional

Funder types: Other

Identifiers

NCT03196362

20160145

Details and patient eligibility

About

Short-term intensive insulin therapy (SIIT) induces glycemic remission in patients with newly diagnosed type 2 diabetes. But remission rate reduces over time. This study aims to investigate whether sequential treatments using fixed dose combination of pioglitazone/metformin (15mg/500mg) after SIIT can improve clinical outcomes inpatients with newly diagnosed type 2 diabetes.

We plan to include 50 patients with newly diagnosed type 2 diabetes who are drug naïve and meet the inclusive criteria will be enrolled. After baseline assessments, SIIT will be applied to all patients using insulin pump to achieve and maintain euglycemia for 2 weeks. After completion of intensive treatment, insulin pump will be stopped. Patients were randomly assigned into either of the following two groups: PIO/MET group: pioglitazone/metformin (15mg/500mg) will be orally administrated twice daily to the subjects for 12 weeks; placebo group: placebo is given twice daily to all subjects for 12 weeks. Afterwards, patients will be followed up for 48 weeks. Primary endpoint is difference in remission rate at the end of study. Secondary endpoints include proportion of patients who achieve glycosylated hemoglobin A1C <7% at the end of study; differences in β-cell function , insulin sensitivity and incidence of adverse events among treatment groups.

Enrollment: 50 estimated patients

Sex: All

Ages: 25 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Patients with newly diagnosed type 2 diabetes who have never received any hypoglycemic treatment;
2. Fasting plasma glucose (FPG) between 7.0 mmol/l (126 mg/dl) and 16.7 mmol/l (300 mg/dl); glycosylated hemoglobin A1C>8.5%;
3. Aged between 25 and 65 years,
4. Body mass index (BMI) 22-35 kg/m2.

Exclusion criteria

1. Type 1 diabetes or special type of diabetes;
2. Acute diabetic complications of diabetes (DKA, HHS and lactic acidosis etc.)
3. Serious microvascular complications: proliferative stage of retinopathy; urine AER >300 mg/g or urine protein positive, quantification >0.5 g/d; uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy;
4. Severe macrovascular complications: acute cerebrovascular accident, acute coronary syndrome, vascular intervention for peripheral arterial disease or amputation requiring hospitalization within 12 months prior to enrollment;
5. Persistently increased blood pressure >180/110 mmHg;
6. Blood creatinine clearance less than 50 ml/min, alanine aminotransferase ≥2.5×upper limit of normal, total bilirubin ≥1.5×upper limit of normal;
7. Hemoglobin <100 g/L or need regular blood transfusion;
8. Use of drugs that may influence blood glucose within 12 weeks;
9. Systemic infection or serious concomitant disease; patients with malignancy or chronic diarrhea;
10. Uncontrolled endocrine gland dysfunction;
11. Patients with mental or communication disorders;
12. Chronic cardiac insufficiency, heart function class III and above;
13. Pregnant women, lactating women and women of child bearing age who are not willing to take contraception during the study;
14. Subjects who don't cooperate, cannot be followed up or have difficulty in completing the study considered by the investigator.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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50 participants in 2 patient groups, including a placebo group

PIO/MET

Active Comparator group

Description:

one fixed dose pioglitazone/metformin (15mg/500mg) tablet will be orally administrated twice daily

Treatment:

Drug: Pioglitazone + Metformin

placebo

Placebo Comparator group

Description:

one tablet of placebo will be given twice daily

Treatment:

Drug: Placebo Oral Tablet