Adding Sitagliptin or Pioglitazone to Type 2 Diabetes Mellitus Insufficiently Controlled With Metformin and Sulfonylurea

Study Overview
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Brief Summary
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This 24-weeks study will to compare the glycemic efficacy and safety of sitagliptin with pioglitazone in patients with type 2 diabetes who had inadequate glycemic control despite dual therapy with metformin and a sulfonylurea.

Detailed Description
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This is a prospective, open-label, randomized, parallel, 24-week study. Inclusion criteria: type 2 diabetes patients who were treated with stable doses of sulfonylurea and metformin to their half maximally dose (sulfonylureas > half maximal dose, and metformin > 1500 mg/d) for > 10 weeks. > 20 years old; A1C:> 7.0 % and < 11% Exclusion criteria: insulin use within 12 weeks of the screening visit, any contraindications for use of sitagliptin or pioglitazone, impaired renal function (serum creatinine > 1.4 mg/dl), alanine aminotransferase (ALT) or aspartate aminotransferase levels (AST) > 2.5 times the upper limit of normal (ULN), current or prepare to pregnancy and lactation. Primary Purpose: compare the change in hemoglobin A1c and the proportion of patients achieving A1C < 7% between the 2 groups Secondary Purposes: Changes in fasting plasma glucose, high sensitive C-reactive protein (hsCRP) Homeostasis model assessment-β cell function(HOMA-β) will be calculated to assess changes in β-cell function and HOMA-insulin resistance(HOMA-IR)to assess changes in insulin resistance Body weight change, proportion of side effects

Official Title
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Efficacy of Adding Sitagliptin or Pioglitazone to Patients With Type 2 Diabetes Insufficiently Controlled With Metformin and Sulfonylurea

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: pioglitazone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes patients who were treated with stable doses of sulfonylurea and metformin to their half maximally dose (sulfonylureas > half maximal dose, and metformin > 1500 mg/d) for > 10 weeks > 20 years old A1C: > 7.0 % and < 11% Exclusion Criteria: Insulin use within 12 weeks of the screening visit Any contraindications for use of sitagliptin or pioglitazone, impaired renal function (serum creatinine > 1.4 mg/dl), alanine aminotransferase or aspartate aminotransferase levels > 2.5 times the upper limit of normal Current or prepare to pregnancy and lactation

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: sitagliptin<br>add sitagliptin100mg/d to pre-study OADs | Drug: Sitagliptin<br>* add sitagliptin100mg/d to pre-study OADs<br>* Other names: Januvia;|
| Active Comparator: pioglitazone<br>add pioglitazone 30mg/d to pre-study OADs | Drug: pioglitazone<br>* add pioglitazone 30mg/d to pre-study OADs<br>* Other names: actos;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change in Glycosylated Hemoglobin (A1C) | A1C change from baseline to 24 weeks | 24 weeks | 
| Baseline A1C | baseline A1C | Baseline | 
| The Percentages of Patient Achieving an A1C <7% | The percentages of patient achieving an A1C <7% at endpoint | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in Fasting Plasma Glucose | fasting serum sugar change from baseline to 24 weeks | 24 weeks | 
| Changes in High Sensitive C-reactive Protein | fasting high sensitive serum C-reactive protein change from baseline to 24 weeks | 24 weeks | 
| Changes in Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR) | HOMA-IR change from baseline to 24 weeks | 24 weeks | 
| Body Weight Change | body weight change from baseline to 24 weeks | 24 weeks | 
| Percentages of Patients With Total Adverse Events (AE) | percentages of total adverse events | 24 weeks | 
| Change in Fasting Total-cholesterol | Total-cholesterol change from baseline to 24 weeks | 24 weeks | 
| Change in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | LDL-C change from baseline to 24 weeks | 24 weeks | 
| Change in Fasting Triglycerides(TG) | TG change from baseline to 24 weeks | 24 weeks | 
| Change in Fasting High-density Lipoprotein Cholesterol(HDL-C) | HDL-C change from baseline to 24 weeks | 24 weeks | 
| Change in Fasting Plasma Alanine-aminotransferase (ALT) | ALT change from baseline to 24 weeks | 24 weeks | 
| Percentages of Patients With Mild to Moderate Hypoglycemia | Incidence of mild to moderate hypoglycemia after treatment | 24 weeks | 
| Percentages of Patients With Edema | proportion of edema after treatment | 24 weeks | 
| Percentages of Patients With Gastrointestinal Adverse Events | Proportion of Gastrointestinal adverse events after treatment | 24 weeks | 
| Percentages of Patients With Nasopharyngitis | Proportion of Nasopharyngitis after treatment | 24 weeks | 
| Percentages of Patients With Severe Hypoglycemia | Proportion of severe hypoglycemia after treatment | 24 weeks | 
| Baseline Fasting Plasma Glucose | Baseline fasting plasma glucose | baseline | 
| Baseline High Sensitive C-reactive Protein | Baseline high sensitive C-reactive Protein | baseline | 
| Baseline Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Baseline HOMA-IR | Baseline HOMA-IR | 
| Baseline Alanine-aminotransferase (ALT) | Baseline alanine-aminotransferase | Baseline | 
| Baseline Body Weight | Baseline body weight | Baseline | 
| Baseline Total Cholesterol | Baseline Total cholesterol | Baseline | 
| Baseline Triglyceride (TG) | Baseline TG | Baseline | 
| Baseline Low-density Lipoprotein Cholesterol (LDL-C) | Baseline LDL-C | Baseline | 
| Baseline High-density Lipoprotein Cholesterol (HDL-C) | Baseline HDL-C | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sitagliptin, pioglitazone, type 2 diabetes