Comparison of Pioglitazone Versus Glimepiride in Type 2 Diabetes Inadequately Controlled With Metformin Plus Alogliptin

Type 2 Diabetes Mellitus Clinical Trial

Official title: A Phase IV, Multicenter, Randomized, Active Comparator Controlled Study of the Addition of Pioglitazone Compared With Glimepiride in Subjects With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Metformin and Alogliptin

Status Recruiting

Clinical Trial Summary

The purpose of this study is to compare the treatment effect at week 26 between the two groups, sulfonylurea (SU, glimepiride) administration and thiazolidinedione (TZD, Pioglitazone) administration, as the third-order drug among patients whose treatment is not sufficient after the combined administration of Metformin and Alogliptin.

Clinical Trial Description

1. Background Complications of diabetes could cause death from stroke and myocardial infarction, and it is the chronic disease that leads to foot amputation, blindness and renal failure. According to the data of Statistics Korea, the prevalence rate of diabetes for people over 30 years old (standardization) has gradually increased from 8.6% in 2001 to 9.7% in 2010. Although diabetes is not the direct cause of death or disability, it is becoming a significant health problem across the world as it is a major illness causing complications.

Diabetic complications are very common; the patients of end-stage renal failure with diabetes were 56.7% and patients who begin renal replacement therapy with diabetes were 70.5% in 2003. The prevalence rate of eye problems including cataract, retinopathies and glaucoma in diabetic patients is 1.9 times higher than that in non-diabetic patients. In addition, it is estimated that the incidence rate of acute stroke, which is a complication of the great vessels of diabetic patients, is also 5.2 times higher than that of the general population. As diabetes could cause various complications and be dangerous, the regulation of blood glucose level is essential in order to prevent these complications.

According to the Korea National Health & Nutrition Examination Survey in 2008~2010, the rate of patients with well-controlled glycated hemoglobin of below 6.5% among diabetic patients over 30 years old is only 25%. Thus, many studies are being conducted to lower the glycated hemoglobin by administering various line drugs, alone or in combination, because the regulation of blood glucose is difficult for many diabetic patients.

When the regulation of blood glucose ends in failure with a single dose of a drug, the combination treatment is recommended. Metformin is mainly used as the first-order treatment drug, and the second and third drugs, such as dipeptidyl peptidase-4 (DPP-4) inhibitor and sulphonylurea, are recommended to use if the first one is not sufficient.

DPP-4 inhibitor is a new line of hypoglycemic agent based on incretin. It has statistically significant results for the regulation of glycated hemoglobin compared to existing oral hypoglycemic agents.

Therefore, many clinicians use Metformin as the first-order drug, and DPP-4 inhibitor as the second-order drug. Alogliptin, which was recently proved to have no side effects of the cardiovascular system, is effective in the regulation of blood glucose as well as the weight control and the prevention of hypoglycemia. Moreover, it is effective when administered alone, and also effective when coadministered with Metformin, Glibenclamide and Pioglitazone. In particular, the reduction degree of glycated hemoglobin was significantly larger when it was administered with Pioglitazone.

Sulphonylurea, the most well-known hypoglycemic agent, is helpful in the regulation of blood glucose and reduces the occurrence frequency of hypoglycemia when combined with Metformin.

2. Rationale This study examines the related factors of the Pioglitazone group, which is a TZDs line, and the Glimepiride group, which is a sulphonylurea line, as the third-order drugs for patients who are coadministered Metformin and Alogliptin, a DPP-4 inhibitor.

3. Hypothesis When the SU and TZDs drugs administered as third-order drugs in the patients who administered second-order drugs, the treatment effect is different between the two drugs

4. Primary Aim/Objective:

The primary objective is to compare the mean changes of HbA1c at week 26 between the two groups, SU (glimepiride) administration and TZDs (Pioglitazone) administration, as the third-order drug among patients whose treatment is not sufficient after the combined administration of Metformin and Alogliptin.

5. Primary Endpoint(s):

The mean changes of HbA1c at week 26 from baseline ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes Mellitus

• NCT number: NCT02426294
• Study type: Interventional
• Source: Pusan National University Hospital
• Contact: Sang Soo Kim, MD., PhD.
• Phone: +82-51-240-7228
• Email: drsskim7@gmail.com
• Status: Recruiting
• Phase: Phase 4
• Start date: February 2015
• Completion date: May 2016