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

Impacts of Sequential Treatment Using Fixed Dose Pioglitazone/Metformin Combination Following Short-term Intensive Insulin Treatment on Long-term Blood Glucose Control and β-Cell Function in Patients With Newly Diagnosed Type 2 Diabetes

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.

Study Overview

• Status: Unknown
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Pioglitazone + Metformin; Drug: Placebo Oral Tablet

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510080
      • Recruiting
      • endocrinology department of the first affiliated hospital of Sun Yat-sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PIO/MET; one fixed dose pioglitazone/metformin (15mg/500mg) tablet will be orally administrated twice daily	Drug: Pioglitazone + Metformin; One tablet of fixed dose of Pioglitazone/ Metformin (15mg/30mg) will be given twice daily
Placebo Comparator: placebo; one tablet of placebo will be given twice daily	Drug: Placebo Oral Tablet; One tablet of placebo will be given twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Remission rate	Remission rate at the end of the study in each group	48 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2016
• Primary Completion (Anticipated): September 30, 2018
• Study Completion (Anticipated): December 31, 2018

Study Registration Dates

• First Submitted: June 20, 2017
• First Submitted That Met QC Criteria: June 20, 2017
• First Posted (Actual): June 22, 2017

Study Record Updates

• Last Update Posted (Actual): June 22, 2017
• Last Update Submitted That Met QC Criteria: June 20, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: remission; metformin; pioglitazone; sequential therapy; short-term intensive insulin therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Pioglitazone
• Other Study ID Numbers: 20160145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No