Diabetes Mellitus, Non-Insulin-Dependent
Conditions
Brief summary
To compare the efficacy of three strategies of lifestyle changes associated with Januvia (sitagliptin) 100 mg/day in patients with Type 2 Diabetes Mellitus (T2DM) inadequately controlled by metformin (hemoglobin A1c \[HbA1c\] 6.5-9%). A difference between the three strategies of lifestyle changes was expected.
Interventions
DRUGsitagliptin phosphate
sitagliptin 100 mg once daily. Duration of treatment: 26 Weeks
BEHAVIORALComparator: Diet
Diet
BEHAVIORALComparator: Physical Activity
Physical Activity
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Man or woman aged \>/= 18 years,with T2DM and treated with the maximal tolerated dose of metformin, with documented or high likely inadequate control of diabetes (HbA1c 6.5-9%)
Exclusion criteria
* Daily insulin treatment or one insulin dose or more within the last 8 weeks or expected insulin treatment within the next 3 months. * Hypoglycemia unawareness or recurrent major hypoglycemia or history of acidoketosis * Known hypersensitivity or contraindication to metformin
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1c Measurement | Baseline and Week 24 | Hemoglobin A1c (HbA1c) is a measure of glycated hemoglobin in the blood. HbA1c greater than 6.5% was considered inadequately controlled. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Fasting Plasma Glucose (FPG) Measurement | Baseline and Week 24 | Generally FPG values of \ 5.0-7.2 mmol/L would be considered goal (American Diabetes Association). |
Participant flow
Pre-assignment details
1512 subjects were selected/screened, 380 subjects failed screening, leaving 1132 subjects who were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin With Standard of Care Subjects received sitagliptin 100 mg once daily for 26 Weeks,
and:
No specific intervention (standard recommendation) on physical exercise and diet. | 362 |
| Sitagliptin With Diet Advice Subjects received sitagliptin 100 mg once daily for 26 Weeks,
and:
Intervention on diet which includes advice on diet with a leaflet and a diary | 358 |
| Sitagliptin With Diet and Physical Activity Advice Subjects received sitagliptin 100 mg once daily for 26 Weeks,
and:
Intervention on diet + physical activity which includes advice on diet and physical activity with leaflets and diaries PLUS advice on physical activity with the utilization of a pedometer: subjects were asked to walk 10,000 steps per day 5 or more days per week. | 265 |
| Total | 985 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Only one reason for discontinuation | 62 | 61 | 48 |
| Overall Study | Two or more reasons for discontinuation | 17 | 19 | 8 |
Baseline characteristics
| Characteristic | Sitagliptin With Standard of Care | Sitagliptin With Diet Advice | Sitagliptin With Diet and Physical Activity Advice | Total |
|---|---|---|---|---|
| Age, Continuous | 58.26 years STANDARD_DEVIATION 10.04 | 57.47 years STANDARD_DEVIATION 9.12 | 57.30 years STANDARD_DEVIATION 9.9 | 57.71 years STANDARD_DEVIATION 9.68 |
| Sex: Female, Male Female | 181 Participants | 175 Participants | 126 Participants | 482 Participants |
| Sex: Female, Male Male | 181 Participants | 183 Participants | 139 Participants | 503 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 412 | 0 / 414 | 0 / 305 |
| serious Total, serious adverse events | 8 / 412 | 18 / 414 | 7 / 305 |
Outcome results
Primary
Hemoglobin A1c Measurement
Hemoglobin A1c (HbA1c) is a measure of glycated hemoglobin in the blood. HbA1c greater than 6.5% was considered inadequately controlled.
Time frame: Baseline and Week 24
Population: The Full Analysis Set (FAS) population included all selected patients with at least one measured HbA1c value after Visit 2 and having received at least one dose of sitagliptin. In the Standard of Care group, only 360 subjects had HbA1c Baseline evaluations.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin With Standard of Care | Hemoglobin A1c Measurement | Baseline (n=360, 358, and 265, respectively) | 7.37 percent HbA1c | Standard Deviation 0.61 |
| Sitagliptin With Standard of Care | Hemoglobin A1c Measurement | Week 24 (n=362, 358, and 265, respectively) | 7.33 percent HbA1c | Standard Deviation 1.09 |
| Sitagliptin With Diet Advice | Hemoglobin A1c Measurement | Baseline (n=360, 358, and 265, respectively) | 7.50 percent HbA1c | Standard Deviation 0.66 |
| Sitagliptin With Diet Advice | Hemoglobin A1c Measurement | Week 24 (n=362, 358, and 265, respectively) | 7.42 percent HbA1c | Standard Deviation 1.15 |
| Sitagliptin With Diet and Physical Activity Advice | Hemoglobin A1c Measurement | Baseline (n=360, 358, and 265, respectively) | 7.49 percent HbA1c | Standard Deviation 0.6 |
| Sitagliptin With Diet and Physical Activity Advice | Hemoglobin A1c Measurement | Week 24 (n=362, 358, and 265, respectively) | 7.40 percent HbA1c | Standard Deviation 1.07 |
Secondary
Fasting Plasma Glucose (FPG) Measurement
Generally FPG values of \ 5.0-7.2 mmol/L would be considered goal (American Diabetes Association).
Time frame: Baseline and Week 24
Population: FAS population. Furthermore, only 350, 252, and 350 subjects had FPG evaluations in the Diet advice, Diet \& physical activity advice, and Standard groups, respectively, at Baseline; and 303, 224, and 310 subjects had FPG evaluations in the Diet advice, Diet \& physical activity advice, and Standard groups, respectively, at Week 24.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sitagliptin With Standard of Care | Fasting Plasma Glucose (FPG) Measurement | Baseline (n=350, 350, 252, respectively) | 8.87 mmol/L glucose | Standard Deviation 1.98 |
| Sitagliptin With Standard of Care | Fasting Plasma Glucose (FPG) Measurement | Week 24 (n=310, 303, and 224, respectively) | 8.21 mmol/L glucose | Standard Deviation 2.07 |
| Sitagliptin With Diet Advice | Fasting Plasma Glucose (FPG) Measurement | Baseline (n=350, 350, 252, respectively) | 9.00 mmol/L glucose | Standard Deviation 2.03 |
| Sitagliptin With Diet Advice | Fasting Plasma Glucose (FPG) Measurement | Week 24 (n=310, 303, and 224, respectively) | 8.32 mmol/L glucose | Standard Deviation 2.08 |
| Sitagliptin With Diet and Physical Activity Advice | Fasting Plasma Glucose (FPG) Measurement | Baseline (n=350, 350, 252, respectively) | 8.91 mmol/L glucose | Standard Deviation 1.87 |
| Sitagliptin With Diet and Physical Activity Advice | Fasting Plasma Glucose (FPG) Measurement | Week 24 (n=310, 303, and 224, respectively) | 8.47 mmol/L glucose | Standard Deviation 2.17 |