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

Phase 4

• Conditions: Type 2 Diabetes Mellitus
• Interventions: Drug: Pioglitazone + Metformin; Drug: Placebo Oral Tablet

• Registration Number: NCT03196362
• Lead Sponsor: Sun Yat-sen University

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2016-12-01
• Status Verified: 2017-06
• Study First Submitted: 2017-06-20
• Study First Submitted QC: 2017-06-20
• Last Update Submitted: 2017-06-20
• Study First Posted: 2017-06-22
• Last Update Posted: 2017-06-22
• Primary Completion: 2018-09-30
• Study Completion: 2018-12-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 50

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
PIO/MET	Pioglitazone + Metformin	one fixed dose pioglitazone/metformin (15mg/500mg) tablet will be orally administrated twice daily
placebo	Placebo Oral Tablet	one tablet of placebo will be given twice daily

Primary Outcome Measures

Name	Time	Method
Remission rate	48 weeks	Remission rate at the end of the study in each group

Secondary Outcome Measures

Name	Time	Method
β-cell function	48 weeks	Difference in β-cell secretion capacity at the end of follow up between treatment groups
Insulin sensitivity	48 weeks	Difference in insulin sensitivity at the end of follow up between treatment groups
glycemic control	48 weeks	proportion of patients who achieve A1C\<7% at the end of follow-up
Adverse events	48 weeks	difference in AEs at the end of follow-up between treatment groups

Trial Locations

Locations (1)

endocrinology department of the first affiliated hospital of Sun Yat-sen University; 🇨🇳 Guangzhou, Guangdong, China