Type 2 Diabetes
Conditions
Keywords
sitagliptin, pioglitazone, type 2 diabetes
Brief summary
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
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: 1. Changes in fasting plasma glucose, high sensitive C-reactive protein (hsCRP) 2. 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 3. Body weight change, proportion of side effects
Interventions
DRUGSitagliptin
add sitagliptin100mg/d to pre-study OADs
DRUGpioglitazone
add pioglitazone 30mg/d to pre-study OADs
Sponsors
Mackay Memorial Hospital
Sung-Chen Liu
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change in Glycosylated Hemoglobin (A1C) | 24 weeks | A1C change from baseline to 24 weeks |
| Baseline A1C | Baseline | baseline A1C |
| The Percentages of Patient Achieving an A1C <7% | 24 weeks | The percentages of patient achieving an A1C \<7% at endpoint |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Body Weight Change | 24 weeks | body weight change from baseline to 24 weeks |
| Percentages of Patients With Total Adverse Events (AE) | 24 weeks | percentages of total adverse events |
| Change in Fasting Total-cholesterol | 24 weeks | Total-cholesterol change from baseline to 24 weeks |
| Change in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | 24 weeks | LDL-C change from baseline to 24 weeks |
| Change in Fasting Triglycerides(TG) | 24 weeks | TG change from baseline to 24 weeks |
| Change in Fasting High-density Lipoprotein Cholesterol(HDL-C) | 24 weeks | HDL-C change from baseline to 24 weeks |
| Change in Fasting Plasma Alanine-aminotransferase (ALT) | 24 weeks | ALT change from baseline to 24 weeks |
| Percentages of Patients With Mild to Moderate Hypoglycemia | 24 weeks | Incidence of mild to moderate hypoglycemia after treatment |
| Percentages of Patients With Edema | 24 weeks | proportion of edema after treatment |
| Percentages of Patients With Gastrointestinal Adverse Events | 24 weeks | Proportion of Gastrointestinal adverse events after treatment |
| Changes in Fasting Plasma Glucose | 24 weeks | fasting serum sugar change from baseline to 24 weeks |
| Percentages of Patients With Severe Hypoglycemia | 24 weeks | Proportion of severe hypoglycemia after treatment |
| Baseline Fasting Plasma Glucose | baseline | Baseline fasting plasma glucose |
| Baseline High Sensitive C-reactive Protein | baseline | Baseline high sensitive C-reactive Protein |
| Baseline Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR) | Baseline HOMA-IR | Baseline HOMA-IR |
| Baseline Alanine-aminotransferase (ALT) | Baseline | Baseline alanine-aminotransferase |
| Baseline Body Weight | Baseline | Baseline body weight |
| Baseline Total Cholesterol | Baseline | Baseline Total cholesterol |
| Baseline Triglyceride (TG) | Baseline | Baseline TG |
| Baseline Low-density Lipoprotein Cholesterol (LDL-C) | Baseline | Baseline LDL-C |
| Baseline High-density Lipoprotein Cholesterol (HDL-C) | Baseline | Baseline HDL-C |
| Percentages of Patients With Nasopharyngitis | 24 weeks | Proportion of Nasopharyngitis after treatment |
| Changes in High Sensitive C-reactive Protein | 24 weeks | fasting high sensitive serum C-reactive protein change from baseline to 24 weeks |
| Changes in Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR) | 24 weeks | HOMA-IR change from baseline to 24 weeks |
Countries
Taiwan
Participant flow
Recruitment details
The study was started from 01 OCT 2009 to 27 SEP 2011
Pre-assignment details
we screened 135 patients and 120 patients were randomized in a 1: 1 ratio to one of the treatment groups. reson for excluded: 4 patients: ALT or AST \>2.5x ULN 8 patiens : withdraw informed consent 3 patiens: baseline A1C\>11%
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin add sitagliptin100mg/d to pre-study OADs | 60 |
| Pioglitazone add pioglitazone 30mg/d to pre-study OADs | 60 |
| Total | 120 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 2 |
| Overall Study | Lost to Follow-up | 2 | 2 |
| Overall Study | Protocol Violation | 3 | 4 |
Baseline characteristics
| Characteristic | Pioglitazone | Sitagliptin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 11 Participants | 18 Participants | 29 Participants |
| Age, Categorical Between 18 and 65 years | 49 Participants | 42 Participants | 91 Participants |
| Age Continuous | 58.1 years STANDARD_DEVIATION 8.3 | 60.1 years STANDARD_DEVIATION 8.9 | 59.1 years STANDARD_DEVIATION 8.6 |
| Region of Enrollment Taiwan | 60 participants | 60 participants | 120 participants |
| Sex: Female, Male Female | 37 Participants | 38 Participants | 75 Participants |
| Sex: Female, Male Male | 23 Participants | 22 Participants | 45 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 26 / 60 | 31 / 60 |
| serious Total, serious adverse events | 0 / 60 | 0 / 60 |
Outcome results
Primary
Baseline A1C
baseline A1C
Time frame: Baseline
Population: baseline Laboratory measurements
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline A1C | 8.27 percentage of Hb | Standard Deviation 0.86 |
| Pioglitazone | Baseline A1C | 8.54 percentage of Hb | Standard Deviation 0.97 |
Primary
Mean Change in Glycosylated Hemoglobin (A1C)
A1C change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Mean Change in Glycosylated Hemoglobin (A1C) | -0.71 percentage of Hb | Standard Error 0.12 |
| Pioglitazone | Mean Change in Glycosylated Hemoglobin (A1C) | -0.94 percentage of Hb | Standard Error 0.12 |
Comparison: The change from baseline in A1C were determined using an analysis of co-variance (ANCOVA) model with the factor 'treatment' and baseline A1C as covariate.p-value: 0.16595% CI: [-0.58, 0.08]ANCOVA
Primary
The Percentages of Patient Achieving an A1C <7%
The percentages of patient achieving an A1C \<7% at endpoint
Time frame: 24 weeks
Population: The percentages of patient achieving an A1C \<7% at endpoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | The Percentages of Patient Achieving an A1C <7% | 28.3 percentage |
| Pioglitazone | The Percentages of Patient Achieving an A1C <7% | 28.8 percentage |
Comparison: Chi-square test for percentages of patient achieving an A1C \<7%p-value: 0.954Chi-squared
Secondary
Baseline Alanine-aminotransferase (ALT)
Baseline alanine-aminotransferase
Time frame: Baseline
Population: Baseline alanine-aminotransferase
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Alanine-aminotransferase (ALT) | 34.2 IU/L | Standard Deviation 17.5 |
| Pioglitazone | Baseline Alanine-aminotransferase (ALT) | 28.5 IU/L | Standard Deviation 15.5 |
Secondary
Baseline Body Weight
Baseline body weight
Time frame: Baseline
Population: Baseline body weight
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Body Weight | 69.4 kg | Standard Deviation 13.6 |
| Pioglitazone | Baseline Body Weight | 65.4 kg | Standard Deviation 10.4 |
Secondary
Baseline Fasting Plasma Glucose
Baseline fasting plasma glucose
Time frame: baseline
Population: Baseline fasting plasma glucose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Fasting Plasma Glucose | 177 mg/dl | Standard Deviation 47 |
| Pioglitazone | Baseline Fasting Plasma Glucose | 182 mg/dl | Standard Deviation 38 |
Secondary
Baseline High-density Lipoprotein Cholesterol (HDL-C)
Baseline HDL-C
Time frame: Baseline
Population: Baseline HDL-C
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline High-density Lipoprotein Cholesterol (HDL-C) | 42 mg/dl | Standard Deviation 12 |
| Pioglitazone | Baseline High-density Lipoprotein Cholesterol (HDL-C) | 43 mg/dl | Standard Deviation 12 |
Secondary
Baseline High Sensitive C-reactive Protein
Baseline high sensitive C-reactive Protein
Time frame: baseline
Population: Baseline high sensitive C-reactive Protein
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline High Sensitive C-reactive Protein | 0.38 mg/dl | Standard Deviation 0.36 |
| Pioglitazone | Baseline High Sensitive C-reactive Protein | 0.42 mg/dl | Standard Deviation 0.68 |
Secondary
Baseline Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR)
Baseline HOMA-IR
Time frame: Baseline HOMA-IR
Population: Baseline HOMA-IR
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR) | 5.6 HOMA-IR score | Standard Deviation 3.8 |
| Pioglitazone | Baseline Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR) | 4.8 HOMA-IR score | Standard Deviation 3.2 |
Secondary
Baseline Low-density Lipoprotein Cholesterol (LDL-C)
Baseline LDL-C
Time frame: Baseline
Population: Baseline LDL-C
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Low-density Lipoprotein Cholesterol (LDL-C) | 102 mg/dl | Standard Deviation 25 |
| Pioglitazone | Baseline Low-density Lipoprotein Cholesterol (LDL-C) | 111 mg/dl | Standard Deviation 31 |
Secondary
Baseline Total Cholesterol
Baseline Total cholesterol
Time frame: Baseline
Population: Baseline Total cholesterol
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Total Cholesterol | 174 mg/dl | Standard Deviation 31 |
| Pioglitazone | Baseline Total Cholesterol | 194 mg/dl | Standard Deviation 33 |
Secondary
Baseline Triglyceride (TG)
Baseline TG
Time frame: Baseline
Population: Baseline TG
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Baseline Triglyceride (TG) | 137 mg/dl | Standard Deviation 74 |
| Pioglitazone | Baseline Triglyceride (TG) | 164 mg/dl | Standard Deviation 73 |
Secondary
Body Weight Change
body weight change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Body Weight Change | -0.26 kg | Standard Error 0.32 |
| Pioglitazone | Body Weight Change | 1.34 kg | Standard Error 0.32 |
Secondary
Change in Fasting High-density Lipoprotein Cholesterol(HDL-C)
HDL-C change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change in Fasting High-density Lipoprotein Cholesterol(HDL-C) | 1.3 mg/dl | Standard Error 1.2 |
| Pioglitazone | Change in Fasting High-density Lipoprotein Cholesterol(HDL-C) | 6.3 mg/dl | Standard Error 1.2 |
Secondary
Change in Fasting Low-density Lipoprotein Cholesterol (LDL-C)
LDL-C change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | -1.2 mg/dl | Standard Error 3.7 |
| Pioglitazone | Change in Fasting Low-density Lipoprotein Cholesterol (LDL-C) | 6.6 mg/dl | Standard Error 3.7 |
Secondary
Change in Fasting Plasma Alanine-aminotransferase (ALT)
ALT change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change in Fasting Plasma Alanine-aminotransferase (ALT) | -0.0 IU/L | Standard Error 2.4 |
| Pioglitazone | Change in Fasting Plasma Alanine-aminotransferase (ALT) | -4.5 IU/L | Standard Error 2.4 |
Secondary
Change in Fasting Total-cholesterol
Total-cholesterol change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change in Fasting Total-cholesterol | 0.6 mg/dl | Standard Error 3.9 |
| Pioglitazone | Change in Fasting Total-cholesterol | 9.9 mg/dl | Standard Error 4 |
Secondary
Change in Fasting Triglycerides(TG)
TG change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Change in Fasting Triglycerides(TG) | 6.3 mg/dl | Standard Error 9.3 |
| Pioglitazone | Change in Fasting Triglycerides(TG) | -23.9 mg/dl | Standard Error 9.4 |
Secondary
Changes in Fasting Plasma Glucose
fasting serum sugar change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat (ITT) analysis with last observation carried forward was used to assess efficacy.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Changes in Fasting Plasma Glucose | -23 mg/dl | Standard Error 4 |
| Pioglitazone | Changes in Fasting Plasma Glucose | -36 mg/dl | Standard Error 4 |
Secondary
Changes in High Sensitive C-reactive Protein
fasting high sensitive serum C-reactive protein change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Changes in High Sensitive C-reactive Protein | -0.07 mg/dl | Standard Error 0.04 |
| Pioglitazone | Changes in High Sensitive C-reactive Protein | -0.19 mg/dl | Standard Error 0.04 |
Secondary
Changes in Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR)
HOMA-IR change from baseline to 24 weeks
Time frame: 24 weeks
Population: An intent-to-treat analysis with last observation carried forward was used to assess efficacy
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin | Changes in Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR) | -0.00 HOMA-IR score | Standard Error 0.35 |
| Pioglitazone | Changes in Homoeostasis Model Assessment of Insulin Resistance (HOMA-IR) | -1.56 HOMA-IR score | Standard Error 0.35 |
Secondary
Percentages of Patients With Edema
proportion of edema after treatment
Time frame: 24 weeks
Population: All patients who had taken at least one dose of study medication were included in the safety analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentages of Patients With Edema | 0 percentage |
| Pioglitazone | Percentages of Patients With Edema | 27.1 percentage |
Secondary
Percentages of Patients With Gastrointestinal Adverse Events
Proportion of Gastrointestinal adverse events after treatment
Time frame: 24 weeks
Population: All patients who had taken at least one dose of study medication were included in the safety analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentages of Patients With Gastrointestinal Adverse Events | 20.0 percentge |
| Pioglitazone | Percentages of Patients With Gastrointestinal Adverse Events | 6.8 percentge |
Secondary
Percentages of Patients With Mild to Moderate Hypoglycemia
Incidence of mild to moderate hypoglycemia after treatment
Time frame: 24 weeks
Population: All patients who had taken at least one dose of study medication were included in the safety analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentages of Patients With Mild to Moderate Hypoglycemia | 10 percentage |
| Pioglitazone | Percentages of Patients With Mild to Moderate Hypoglycemia | 8.5 percentage |
Secondary
Percentages of Patients With Nasopharyngitis
Proportion of Nasopharyngitis after treatment
Time frame: 24 weeks
Population: All patients who had taken at least one dose of study medication were included in the safety analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentages of Patients With Nasopharyngitis | 20.0 percentage |
| Pioglitazone | Percentages of Patients With Nasopharyngitis | 18.6 percentage |
Secondary
Percentages of Patients With Severe Hypoglycemia
Proportion of severe hypoglycemia after treatment
Time frame: 24 weeks
Population: Proportion of severe ypoglycemia after treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentages of Patients With Severe Hypoglycemia | 0 percentage |
| Pioglitazone | Percentages of Patients With Severe Hypoglycemia | 0 percentage |
Secondary
Percentages of Patients With Total Adverse Events (AE)
percentages of total adverse events
Time frame: 24 weeks
Population: All patients who had taken at least one dose of study medication were included in the safety analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin | Percentages of Patients With Total Adverse Events (AE) | 43.1 percentage |
| Pioglitazone | Percentages of Patients With Total Adverse Events (AE) | 51.7 percentage |