Diabetes
Conditions
Keywords
type 2 diabetes, new onset, combination therapy, new onset type 2 diabetes
Brief summary
Type 2 diabetes is a systemic metabolic disease with significant morbidity and mortality due to damaging blood vessels. Increased blood sugar level is a hallmark of diabetes and is an contributes to the development of many of its complications. Multiple defects, e.g. impaired insulin secretion and impaired insulin action, contribute to the development of the disease. The aim of this study is to test the efficacy and durability of combination of drugs which correct the defects that lead to the development of diabetes on achieving adequate and durable control of blood sugar levels. Achieving adequate and durable control of blood sugar will prevent many of diabetes complications.
Detailed description
Subjects will be randomized (using a table of random numbers) to receive, in open label fashion, one of the following treatment regimens: (i) Group I will be started on pioglitazone (15 mg/day) plus metformin (1000 mg/day) with the supper meal and exenatide (5 mcg s.c. bid 30 min before breakfast and supper) and up-titrated to 45 pioglitazone plus 2000 metformin and 10 mcg s.c. bid exenatide to achieve HbA1c \<6.0%; (II) Group II will be started on metformin, 1000 mg with breakfast and 1000 mg with supper, glyburide and basal insulin will be added and up titrated to achieve HbA1c \<6.0% The study team will compare the efficacy of two therapeutic regimens: (i) triple therapy (pioglitazone, metformin, exenatide) at the time of diagnosis of T2DM versus (ii) stepwise therapy starting with metformin and subsequent addition of sulfonylurea and basal insulin (i.e., the standard approach) in achieving this goal. The first intervention is based on the novel concept of initiating therapy at the time of diagnosis with combination therapy using agents that correct specific pathophysiologic defects that are characteristic of T2DM (insulin resistance and beta cell failure). The second intervention is based upon stepwise addition of antidiabetic agents to reduce the HbA1C according to the current ADA therapeutic recommendation.
Interventions
DRUGmetformin\pioglitazone\exenatide
metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5%
DRUGmetformin, glyburide and glargine
subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \< 6.5%
Sponsors
American Diabetes Association
Amylin Pharmaceuticals, LLC.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
The University of Texas Health Science Center at San Antonio
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* subjects with type 2 diabetes diagnosed during the past 2 years, * above 18 years of age, * drug naive, or have been on metformin less than 3 months
Exclusion criteria
* subjects with type 1 diabetes or GAD positive subjects or subjects with long standing diabetes (\>2 years) or subjects who are not drug naive or have been on metformin more than 3 months.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c Level | at the end of the study (3 years) | subjects will be followed for 3 years and the HbA1c measured at this time to provide the values for each arm as defined for the primary outcome of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Failure | 3 years | Number of participants with HbA1c\>6.5% at 3 years |
| Percentage of Patients With Reported Hypoglycemic Events | during the entire study (3 years) | asymptomatic hypoglycemic events with documented PGC \< 60 mg/dl and sympotomatic hypoglycemia |
Countries
United States
Participant flow
Recruitment details
Newly diagnosed T2DM participants
Participants by arm
| Arm | Count |
|---|---|
| Triple Therapy initiation a combination of metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) at the time diabetes is diagnosed
metformin\\pioglitazone\\exenatide: metformin (1000 mg), pioglitazone (15 mg) and exenatide (5 microgram bid) are started and dose is up titrated to achieve HbA1c \< 6.5% | 103 |
| Conventional Therapy sequential addition of metformin, glyburide and basal insulin
metformin, glyburide and glargine: subjects are started on metformin 500 mg bid and dose is up titrated and glyburide (up to 5 mg) and glargine are sequentially added to maintain HbA1c \< 6.5% | 114 |
| Total | 217 |
Baseline characteristics
| Characteristic | Triple Therapy | Conventional Therapy | Total |
|---|---|---|---|
| Age, Continuous | 44 years STANDARD_DEVIATION 1 | 47 years STANDARD_DEVIATION 1 | 45.5 years STANDARD_DEVIATION 1 |
| Baseline HbA1c | 9.0 percentage of glycated hemoglobin STANDARD_DEVIATION 0.2 | 8.8 percentage of glycated hemoglobin STANDARD_DEVIATION 0.2 | 8.9 percentage of glycated hemoglobin STANDARD_DEVIATION 0.2 |
| Body Mass Index (BMI) | 36.4 kg/m^2 STANDARD_DEVIATION 1.1 | 36.1 kg/m^2 STANDARD_DEVIATION 1.1 | 36.25 kg/m^2 STANDARD_DEVIATION 1.1 |
| Diabetes Duration at start | 4.8 Months STANDARD_DEVIATION 0.5 | 5.2 Months STANDARD_DEVIATION 0.5 | 5 Months STANDARD_DEVIATION 0.5 |
| Fasting Plasma Glucose | 203 mg/dl STANDARD_DEVIATION 6 | 200 mg/dl STANDARD_DEVIATION 6 | 201.5 mg/dl STANDARD_DEVIATION 6 |
| Race/Ethnicity, Customized Caucasian | 15 participants | 15 participants | 30 participants |
| Race/Ethnicity, Customized Mexican Americans | 73 participants | 75 participants | 148 participants |
| Race/Ethnicity, Customized Other | 15 participants | 24 participants | 39 participants |
| Region of Enrollment United States | 103 participants | 114 participants | 217 participants |
| Sex: Female, Male Female | 52 Participants | 72 Participants | 124 Participants |
| Sex: Female, Male Male | 51 Participants | 42 Participants | 93 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 103 | 2 / 114 |
| other Total, other adverse events | 44 / 103 | 53 / 114 |
| serious Total, serious adverse events | 0 / 103 | 0 / 114 |
Outcome results
Primary
HbA1c Level
subjects will be followed for 3 years and the HbA1c measured at this time to provide the values for each arm as defined for the primary outcome of the study
Time frame: at the end of the study (3 years)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triple Therapy | HbA1c Level | 6.9 percentage of glycated hemoglobin | Standard Error 0.1 |
| Conventional Therapy | HbA1c Level | 6.4 percentage of glycated hemoglobin | Standard Error 0.1 |
Secondary
Percentage of Patients With Reported Hypoglycemic Events
asymptomatic hypoglycemic events with documented PGC \< 60 mg/dl and sympotomatic hypoglycemia
Time frame: during the entire study (3 years)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Triple Therapy | Percentage of Patients With Reported Hypoglycemic Events | 14 Participants |
| Conventional Therapy | Percentage of Patients With Reported Hypoglycemic Events | 52 Participants |
Secondary
Treatment Failure
Number of participants with HbA1c\>6.5% at 3 years
Time frame: 3 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Triple Therapy | Treatment Failure | 33 number of participants |
| Conventional Therapy | Treatment Failure | 59 number of participants |