Type 2 Diabetes Mellitus
Conditions
Brief summary
This study will assess the effect of sitagliptin/metformin FDC 50/1000 mg (Janumet®), MK-0431A) compared with the effect of glimepiride on hemoglobin A1c (HbA1c). The primary hypothesis is that after 30 weeks, sitagliptin/metformin FDC 50/1000 mg provides superior reduction in HbA1c (mean change from baseline) compared to glimepiride.
Interventions
DRUGSitagliptin/Metformin FDC
Sitagliptin phosphate plus metformin hydrochloride combination tablet (MK-0431A) orally up to 50/1000 mg BID for 30 weeks
Glimepiride tablet orally up to 6 mg daily for 30 Weeks
DRUGMatching placebo to Sitagliptin/Metformin FDC
Matching placebo to Sitagliptin/Metformin FDC 50/1000 mg orally BID for 30 weeks
Matching placebo to glimepiride tablet orally daily for 30 weeks
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has type 2 diabetes mellitus * Is currently not on an anti-hypoglycemic agent (AHA) (off for at least 12 weeks) and has a Visit 1/Screening Visit HbA1c greater than or equal to 7.0% and less than or equal to 9.5%; or is currently on AHA monotherapy or low-dose oral combination therapy (i.e., less than or equal to 50% maximum labeled dose of each agent) and has a Visit 1/Screening Visit HbA1c greater than or equal to 6.5% and less than or equal to 9.0%
Exclusion criteria
* Has a history of type 1 diabetes mellitus or a history of ketoacidosis * Has been on any investigational or approved glucagon-like peptide-1 (GLP-1) analogue (such as exenatide, liraglutide, etc.), any investigational or approved dipeptidyl peptidase IV (DPP-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, etc.) or a peroxisome proliferator-activated receptor (PPAR) gamma agonist agent (such as rosiglitazone, pioglitazone, etc.) within 12 weeks of Visit 1 * Required insulin within the prior 12 weeks * Has a hypersensitivity or contraindication to any sulfonylurea medication (such as glimepiride, glipizide, etc.), DPP-4 inhibitor (such as sitagliptin, vildagliptin, alogliptin, etc.), or biguanide medication (such as metformin, etc.) * Has inadequately controlled hypertension * Has cirrhosis or active liver disease * Has severe cardiac conditions * Is obese * Has human immunodeficiency virus (HIV)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30 | Baseline and Week 30 | HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Change in A1C following 30 weeks of therapy (i.e., A1C at Week 30 minus A1C at baseline). |
| Number of Participants Who Experienced at Least One Adverse Event (AE) | Up to 32 weeks | An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product. |
| Number of Participants Who Discontinued Study Drug Due to an Adverse Event | Up to 30 weeks | An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30 | Baseline and Week 30 | Blood glucose was measured on a fasting basis (collected after an 8- to 10-hour fast). FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 30 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 30 minus FPG at baseline). |
| Percentage of Participants With HbA1C < 7.0% at Week 30 | Week 30 | HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). |
| Percentage of Participants With One or More Episodes of Hypoglycemia | Up to Week 30 | Symptomatic episodes assessed as likely to be due to hypoglycemia were reported by investigators as adverse experiences of hypoglycemia. Adverse experiences of hypoglycemia were based on all reports of hypoglycemia; a concurrent glucose measurement was not required. |
| Change From Baseline in Body Weight at Week 30 | Baseline and Week 30 | Change in body weight following 30 weeks of therapy (i.e., body weight at Week 30 minus body weight at baseline) |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin/Metformin Participants in the Sitagliptin/Metformin Fixed- Dose Combination (Sita/Met FDC) group received tablets of Sita/Met FDC and placebo tablets matching glimepiride for 30 weeks. The dose for Sita/Met FDC was 50/500 mg twice daily (b.i.d.) starting Day 1 and increased to 50/1000 mg b.i.d. over a period of 4 weeks. | 147 |
| Glimepiride Participants in the Glimepiride group received 2 placebo tablets matching Sita/Met FDC and glimepiride tablets (1 mg or 2 mg) for 30 weeks. The dose for glimepiride was 1 mg once daily (q.d.) starting Day 1 and up-titrated as considered appropriate by the investigator based upon the results of participant's self-monitored blood glucose levels but not to exceed 6 mg/day. | 145 |
| Total | 292 |
Baseline characteristics
| Characteristic | Sitagliptin/Metformin | Glimepiride | Total |
|---|---|---|---|
| Age, Continuous | 54.8 Years STANDARD_DEVIATION 8.5 | 53.1 Years STANDARD_DEVIATION 9.2 | 53.9 Years STANDARD_DEVIATION 8.9 |
| Sex: Female, Male Female | 66 Participants | 61 Participants | 127 Participants |
| Sex: Female, Male Male | 81 Participants | 84 Participants | 165 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 62 / 146 | 54 / 144 |
| serious Total, serious adverse events | 8 / 146 | 9 / 144 |
Outcome results
Primary
Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30
HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%). Change in A1C following 30 weeks of therapy (i.e., A1C at Week 30 minus A1C at baseline).
Time frame: Baseline and Week 30
Population: Full-Analysis-Set (FAS) Population included all randomized participants who had a baseline measurement, consumed at least one dose of study medication, and had at least one post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin | Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30 | -1.5 Percent of total hemoglobin |
| Glimepiride | Change From Baseline in Hemoglobin A1C (HbA1C) at Week 30 | -0.7 Percent of total hemoglobin |
p-value: <0.00195% CI: [-1, -0.6]ANCOVA
Primary
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
An AE is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.
Time frame: Up to 30 weeks
Population: The APaT Population includes all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 8 Participants |
| Glimepiride | Number of Participants Who Discontinued Study Drug Due to an Adverse Event | 8 Participants |
Primary
Number of Participants Who Experienced at Least One Adverse Event (AE)
An adverse event (AE) is any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with study drug administration whether or not considered related to the use of the product.
Time frame: Up to 32 weeks
Population: The All Patients as Treated (APaT) Population includes all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin | Number of Participants Who Experienced at Least One Adverse Event (AE) | 88 Participants |
| Glimepiride | Number of Participants Who Experienced at Least One Adverse Event (AE) | 101 Participants |
Secondary
Change From Baseline in Body Weight at Week 30
Change in body weight following 30 weeks of therapy (i.e., body weight at Week 30 minus body weight at baseline)
Time frame: Baseline and Week 30
Population: The APaT Population includes all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin/Metformin | Change From Baseline in Body Weight at Week 30 | -0.83 kg | 95% Confidence Interval 1.8 |
| Glimepiride | Change From Baseline in Body Weight at Week 30 | 0.90 kg | 95% Confidence Interval 2.4 |
p-value: <0.00195% CI: [-2.2, -1.25]ANCOVA
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30
Blood glucose was measured on a fasting basis (collected after an 8- to 10-hour fast). FPG is expressed as mg/dL. Blood was drawn at predose on Day 1 and after 30 weeks of treatment to determine change in plasma glucose levels (i.e., FPG at Week 30 minus FPG at baseline).
Time frame: Baseline and Week 30
Population: The FAS Population included all randomized participants who had a baseline measurement, consumed at least one dose of study medication, and had at least one post-randomization measurement.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30 | -47.0 mg/dL |
| Glimepiride | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 30 | -23.5 mg/dL |
p-value: <0.00195% CI: [-30, -16.9]ANCOVA
Secondary
Percentage of Participants With HbA1C < 7.0% at Week 30
HbA1C is blood marker used to report average blood glucose levels over a prolonged periods of time and is reported as a percentage (%).
Time frame: Week 30
Population: The FAS Population included all randomized participants who had a baseline measurement, consumed at least one dose of study medication, and had at least one post-randomization measurement.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin | Percentage of Participants With HbA1C < 7.0% at Week 30 | 81.2 Percentage of Participants |
| Glimepiride | Percentage of Participants With HbA1C < 7.0% at Week 30 | 40.1 Percentage of Participants |
p-value: <0.00195% CI: [30, 51]ANCOVA
Secondary
Percentage of Participants With One or More Episodes of Hypoglycemia
Symptomatic episodes assessed as likely to be due to hypoglycemia were reported by investigators as adverse experiences of hypoglycemia. Adverse experiences of hypoglycemia were based on all reports of hypoglycemia; a concurrent glucose measurement was not required.
Time frame: Up to Week 30
Population: The APaT Population includes all randomized participants who received at least 1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin | Percentage of Participants With One or More Episodes of Hypoglycemia | 5.5 Percentage of participants |
| Glimepiride | Percentage of Participants With One or More Episodes of Hypoglycemia | 20.1 Percentage of participants |
p-value: <0.00195% CI: [-23, -7]ANCOVA