Type 2 Diabetes Mellitus
Conditions
Brief summary
The purpose of this study is to assess the effect of the addition of sitagliptin (administered as MK-0431A or MK-0431A XR) relative to the addition of placebo on glycated hemoglobin (A1C), and the safety and tolerability of the addition of sitagliptin, in pediatric participants (ages 10-17 years) with type 2 diabetes mellitus with inadequate glycemic control on metformin therapy (alone or in combination with insulin). The primary hypothesis is that the addition of sitagliptin reduces glycated hemoglobin (A1C) more than the addition of placebo after 20 weeks of treatment.
Interventions
DRUGSitagliptin plus metformin XR
Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1500 mg or 2000 mg of metformin. Dosage of metformin XR was based on each participant's daily metformin dose prior to enrollment.
DRUGPlacebo to metformin XR
Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.
DRUGInsulin
Participants who met protocol-specific glycemic rescue criteria received insulin as glycemic rescue therapy; participants on background insulin had their insulin dose increased for glycemic rescue. During Weeks 20-54, for participants who were not on background insulin or rescued with insulin during Weeks 0-20 in the Sitagliptin/Metformin and Metformin arms (protocol MK-0431A-170), and during Weeks 0-54 for participants not on background insulin in the Sitagliptin/Metformin XR and Metformin XR arms (protocol MK-0431A-289), the type of insulin for glycemic rescue was specified to be insulin glargine.
DRUGPlacebo to sitagliptin plus metformin XR
Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to sitagliptin plus metformin XR.
DRUGMetformin XR
Participants received 2 tablets daily, both taken together with a meal, to provide a total daily dose of 1000 mg, 1500 mg or 2000 mg of metformin XR. Dosage was based on each participant's daily metformin dose prior to enrollment.
DRUGSitagliptin plus metformin
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 100 mg of sitagliptin and 1000 mg, 1700 mg or 2000 mg of metformin. Dosage of metformin was based on each participant's daily metformin dose prior to enrollment.
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.
DRUGMetformin
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal, to provide a total daily dose of 1000 mg, 1700 mg or 2000 mg of metformin. Dosage was based on each participant's daily metformin dose prior to enrollment.
DRUGPlacebo to sitagliptin plus metformin
Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to sitagliptin plus metformin.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants enrolled in protocol MK-0431A-170 were aware that they would receive either sitagliptin and metformin, or metformin. Participants in protocol MK-0431A-289 were aware that they would receive either sitagliptin and metformin XR, or metformin XR.
Intervention model description
Participants enrolled in protocol MK-0431A-170 were randomized between the arms Sitagliptin/Metformin and Metformin. Participants enrolled in protocol MK-0431A-289 were randomized between the arms Sitagliptin/Metformin XR and Metformin XR.
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* For MK-0431A-170 base study and MK-0431A-289: * Has type 2 diabetes mellitus (T2DM) * Is on metformin monotherapy (≥1500 mg/day) for ≥12 weeks with glycated hemoglobin (A1C) ≥6.5% and ≤10.0% OR is on stable doses of metformin (≥1500 mg/day) and insulin for ≥12 weeks with an A1C ≥7.0% and ≤10%. NOTE: Participants on a daily dose of metformin greater than or equal to 1000 mg/day, but less than 1500 mg/day may be eligible if there is documentation that higher doses are not tolerated. * Participant and a family member or adult closely involved in the daily activities will participate in the participant's treatment and study protocol (i.e., available for telephone calls, study visits and administration of study medication as needed). * Male, or female who is unlikely to conceive (non-sterilized, and is not sexually active or agrees to abstain from heterosexual activity or agrees to use an adequate method of contraception) during the study and for 14 days after the last dose of study drug * For MK-0431A-170 extension protocol: * Has completed the P170 base study * Participant and a family member or adult closely involved in the daily activities will participate in the participant's treatment and study protocol (i.e., available for telephone calls, study visits and administration of study medication as needed). * Male, or female who is unlikely to conceive (non-sterilized, and is not sexually active or agrees to abstain from heterosexual activity or agrees to use an adequate method of contraception) during the study and for 14 days after the last dose of study drug
Exclusion criteria
* For MK-0431A-170 base study and MK-0431A-289: * Has type 1 diabetes mellitus * Has monogenic diabetes or secondary diabetes * Has symptomatic hyperglycemia and/or moderate to large ketonuria and/or positive test for ketonemia, requiring immediate initiation of another antihyperglycemic agent * Has previously taken a dipeptidyl peptidase IV (DPP-4) inhibitor (such as sitagliptin, vildagliptin, alogliptin, saxagliptin, or linagliptin) or glucagon-like peptide-1 (GLP-1) receptor agonist (such as exenatide or liraglutide) * Is on or likely to require treatment for ≥2 consecutive weeks or repeated courses of corticosteroids (inhaled, nasal and topical corticosteroids are permitted) * Has undergone a surgical procedure within 4 weeks of study participation or has planned major surgery during the study * History of congenital heart disease or cardiovascular disease other than hypertension * History of active liver disease (other than non-alcoholic steatosis), including chronic active hepatitis B or C, primary biliary cirrhosis, or symptomatic gallbladder disease * Active neuropathy (such as nephrotic syndrome or glomerulonephritis) * Chronic myopathy, mitochondrial disorder or a progressive neurological or neuromuscular disorder * Human immunodeficiency virus (HIV) * Hematological disorder (such as aplastic anemia, thrombocytopenia, myeloproliferative or myelodysplastic syndromes) * Is currently being treated for hyperthyroidism or is on thyroid hormone therapy and has not been on a stable dose for at least 6 weeks * History of malignancy for ≤5 years prior to study participation, except for adequately treated basal cell or squamous cell skin cancer, or in situ cervical cancer * History of idiopathic acute pancreatitis or chronic pancreatitis * History of recreational or illicit drug use, or of alcohol abuse or dependence (within the past year) * Has donated blood products or has had phlebotomy of \>10% of estimated total blood volume within 8 weeks of study participation, or intends to donate blood products or receive blood products within the projected duration of the study * Is pregnant or breast-feeding, or is expecting to conceive or donate eggs during the study, including 14 days following the last dose of study drug * For MK-0431A-170 extension protocol: * Participant meets a study medication discontinuation criterion at the last visit of the MK-0431A-170 base study (Week 20) * Has taken the last dose of study medication for the MK-0431A-170 base study more than 14 days prior to Extension Visit 1 * Has initiated another oral antihyperglycemic agent * Participant does not agree to refrain from participating in any other double-blind interventional study while participating in the P170 extension study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54 | Up to Week 54 | The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Change From Baseline in A1C at Week 20 | Baseline and Week 20 | Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model. |
| Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20 | Up to Week 20 | The number of participants experiencing ≥1 adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20 | Up to Week 20 | The number of participants who discontinued from study drug due to an adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
| Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | Up to approximately Week 56 | The number of participants experiencing ≥1 adverse event during Weeks 0-56 were reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With A1C at Goal (<6.5%) at Week 20 | Week 20 | Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (\<6.5%) at Week 20 was presented. |
| Percentage of Participants With A1C at Goal (<7.0%) at Week 54 | Week 54 | Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (\<7.0%) at Week 54 was presented. |
| Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | Up to Week 20 | Percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported. |
| Percentage of Participants Initiating Insulin Glargine During Weeks 20-54 | Week 20 up to Week 54 | Percentage of participants who initiated insulin glargine therapy from Weeks 20 through 54 was reported. |
| Percentage of Participants With A1C at Goal (<6.5%) at Week 54 | Week 54 | Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (\<6.5%) at Week 54 was presented. |
| Change From Baseline in A1C at Week 54 | Baseline and Week 54 | A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model. |
| Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 | Baseline and Week 20 | Blood glucose was measured on a fasting basis. Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model. |
| Change From Baseline in FPG at Week 54 | Baseline and Week 54 | Blood glucose was measured on a fasting basis. Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model. |
| Percentage of Participants With A1C at Goal (<7.0%) at Week 20 | Week 20 | Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (\<7.0%) at Week 20 was presented. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Baseline A1C | Baseline | Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. |
Participant flow
Recruitment details
The study recruited participants in clinics/clinical offices in 28 countries. One participant who was randomized to the arm Sitagliptin/Metformin withdrew prior to treatment, then was re-randomized into the study. Only the second randomization is counted for Participant Flow and All-Cause Mortality, so this participant is not counted twice.
Pre-assignment details
The Pre-Assignment Period included a one-week single-blind placebo run-in prior to randomization during which participants received metformin with sitagliptin/metformin placebo or metformin XR with sitagliptin/metformin XR placebo each day.
Participants by arm
| Arm | Count |
|---|---|
| Sitagliptin/Metformin Participants received one tablet of sitagliptin/metformin and one tablet of metformin-placebo, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170. | 62 |
| Metformin Participants received one tablet of metformin and one tablet of placebo to sitagliptin/metformin, administered twice daily prior to the morning and evening meals, for up to 20 weeks in the base study alone, or for up to 54 weeks if the participant also entered the extension study. Participants in this arm were enrolled in protocol MK-0431A-170. | 62 |
| Sitagliptin/Metformin XR Participants received two tablets of sitagliptin/metformin XR and two tablets of metformin XR placebo, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289. | 45 |
| Metformin XR Participants received two tablets of metformin XR and two tablets of placebo to sitagliptin/metformin XR, administered once daily with a meal, for up to 54 weeks. Participants in this arm were enrolled in protocol MK-0431A-289. | 51 |
| Total | 220 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Weeks 0-20 | Consent withdrawn by Parent/Guardian | 0 | 0 | 1 | 3 |
| Weeks 0-20 | Lost to Follow-up | 1 | 0 | 1 | 1 |
| Weeks 0-20 | Randomized but not treated | 0 | 0 | 2 | 0 |
| Weeks 0-20 | Withdrawal by Subject | 2 | 0 | 1 | 0 |
| Weeks 20-54 | Consent withdrawn by Parent/Guardian | 1 | 1 | 1 | 0 |
| Weeks 20-54 | Lost to Follow-up | 0 | 0 | 1 | 2 |
| Weeks 20-54 | Withdrawal by Subject | 2 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | Metformin | Sitagliptin/Metformin XR | Metformin XR | Total | Sitagliptin/Metformin |
|---|---|---|---|---|---|
| Age, Continuous | 13.9 years STANDARD_DEVIATION 1.8 | 14.8 years STANDARD_DEVIATION 1.9 | 14.9 years STANDARD_DEVIATION 1.6 | 14.4 years STANDARD_DEVIATION 1.9 | 14.4 years STANDARD_DEVIATION 2.2 |
| Age, Customized 85 years and over | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Adolescents (12-17 years) | 55 Participants | 42 Participants | 50 Participants | 199 Participants | 52 Participants |
| Age, Customized Adults (18-64 years) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Children (2-11 years) | 7 Participants | 3 Participants | 1 Participants | 21 Participants | 10 Participants |
| Age, Customized From 65-84 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Infants and toddlers (28 days-23 months) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized In utero | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Newborns (0-27 days) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized Preterm newborn infants (gestational age < 37 wks) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 23 Participants | 11 Participants | 20 Participants | 77 Participants | 23 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 36 Participants | 29 Participants | 28 Participants | 128 Participants | 35 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants | 5 Participants | 3 Participants | 15 Participants | 4 Participants |
| Glycated Hemoglobin (A1C) | 8.13 Percentage STANDARD_DEVIATION 1.08 | 7.87 Percentage STANDARD_DEVIATION 0.94 | 7.97 Percentage STANDARD_DEVIATION 1.05 | 8.0 Percentage STANDARD_DEVIATION 1.1 | 8.02 Percentage STANDARD_DEVIATION 1.22 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 3 Participants | 9 Participants | 13 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 22 Participants | 15 Participants | 6 Participants | 64 Participants | 21 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 2 Participants | 4 Participants | 10 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 13 Participants | 3 Participants | 5 Participants | 35 Participants | 14 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 23 Participants | 22 Participants | 27 Participants | 96 Participants | 24 Participants |
| Sex: Female, Male Female | 40 Participants | 32 Participants | 32 Participants | 145 Participants | 41 Participants |
| Sex: Female, Male Male | 22 Participants | 13 Participants | 19 Participants | 75 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 62 | 0 / 62 | 0 / 47 | 0 / 51 | 1 / 109 | 0 / 113 |
| other Total, other adverse events | 34 / 62 | 40 / 62 | 30 / 45 | 36 / 51 | 64 / 107 | 76 / 113 |
| serious Total, serious adverse events | 4 / 62 | 3 / 62 | 3 / 45 | 3 / 51 | 7 / 107 | 6 / 113 |
Outcome results
Primary
Change From Baseline in A1C at Week 20
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model.
Time frame: Baseline and Week 20
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication and who had at least 1 measurement of A1C. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Change From Baseline in A1C at Week 20 | -0.58 Percentage of glycated hemoglobin |
| Metformin and Metformin XR Pooled | Change From Baseline in A1C at Week 20 | -0.09 Percentage of glycated hemoglobin |
Comparison: The Least Squares (LS) Mean for the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled.p-value: =0.01895% CI: [-0.9, -0.09]Mixed Models Analysis
Primary
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to Week 20
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20 | 1 Participants |
| Metformin and Metformin XR Pooled | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20 | 2 Participants |
| Sitagliptin/Metformin XR | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20 | 2 Participants |
| Metformin XR | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20 | 2 Participants |
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20 | 3 Participants |
| Metformin and Metformin XR Pooled | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20 | 4 Participants |
Comparison: The percentage of participants who discontinued study drug due to experiencing an adverse event for the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled.95% CI: [-6.2, 5]
Primary
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54
The number of participants who discontinued from study drug due to an adverse event during Weeks 0-54 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to Week 54
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54 | 1 Participants |
| Metformin and Metformin XR Pooled | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54 | 1 Participants |
| Sitagliptin/Metformin XR | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54 | 1 Participants |
| Metformin XR | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54 | 3 Participants |
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54 | 2 Participants |
| Metformin and Metformin XR Pooled | Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54 | 4 Participants |
Comparison: The percentage of participants who discontinued study drug due to experiencing an adverse event for the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled.95% CI: [-10.1, 5.8]
Primary
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20
The number of participants experiencing ≥1 adverse event during Weeks 0-20 was reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to Week 20
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20 | 42 Participants |
| Metformin and Metformin XR Pooled | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20 | 46 Participants |
| Sitagliptin/Metformin XR | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20 | 29 Participants |
| Metformin XR | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20 | 30 Participants |
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20 | 71 Participants |
| Metformin and Metformin XR Pooled | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20 | 76 Participants |
Comparison: The percentage of participants who experienced ≥1 adverse event for the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled.95% CI: [-13.9, 11.3]
Primary
Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56
The number of participants experiencing ≥1 adverse event during Weeks 0-56 were reported. An adverse event is defined as any untoward medical occurrence in a person administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to approximately Week 56
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 26 Participants |
| Metformin and Metformin XR Pooled | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 27 Participants |
| Sitagliptin/Metformin XR | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 36 Participants |
| Metformin XR | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 39 Participants |
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 62 Participants |
| Metformin and Metformin XR Pooled | Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56 | 66 Participants |
Comparison: The percentage of participants who experienced ≥1 adverse event for the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled.95% CI: [-8.9, 14.4]
Secondary
Change From Baseline in A1C at Week 54
A1C is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model.
Time frame: Baseline and Week 54
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication, had ≥1 measurement of A1C, and continued in the study beyond Week 20. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and -289, pooled by receipt of experimental drug or placebo.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Change From Baseline in A1C at Week 54 | 0.35 Percentage of glycated hemoglobin |
| Metformin and Metformin XR Pooled | Change From Baseline in A1C at Week 54 | 0.73 Percentage of glycated hemoglobin |
Secondary
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
Blood glucose was measured on a fasting basis. Mean change from baseline at Week 20 was estimated from a longitudinal data analysis model.
Time frame: Baseline and Week 20
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication, and who had at least 1 measurement of FPG. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 | -2.5 mg/dL |
| Metformin and Metformin XR Pooled | Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20 | 8.3 mg/dL |
Comparison: The Least Squares (LS) Mean for the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled.p-value: =0.15995% CI: [-25.9, 4.3]Mixed Models Analysis
Secondary
Change From Baseline in FPG at Week 54
Blood glucose was measured on a fasting basis. Mean change from baseline at Week 54 was estimated from a longitudinal data analysis model.
Time frame: Baseline and Week 54
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication, had ≥1 measurement of FPG, and continued in the study beyond Week 20. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and -289, pooled by receipt of experimental drug or placebo.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Change From Baseline in FPG at Week 54 | 16.8 mg/dL |
| Metformin and Metformin XR Pooled | Change From Baseline in FPG at Week 54 | 16.9 mg/dL |
Secondary
Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20
Percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported.
Time frame: Up to Week 20
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 3.2 Percentage of participants |
| Metformin and Metformin XR Pooled | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 19.4 Percentage of participants |
| Sitagliptin/Metformin XR | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 4.4 Percentage of participants |
| Metformin XR | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 13.7 Percentage of participants |
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 3.7 Percentage of participants |
| Metformin and Metformin XR Pooled | Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20 | 16.8 Percentage of participants |
Comparison: The percentage of participants initiating glycemic rescue therapy in the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled.p-value: 0.00295% CI: [-21.1, -5.3]Log-Rank Test
Secondary
Percentage of Participants Initiating Insulin Glargine During Weeks 20-54
Percentage of participants who initiated insulin glargine therapy from Weeks 20 through 54 was reported.
Time frame: Week 20 up to Week 54
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20 without initiating glycemic rescue therapy before Week 20. As defined in the protocols, these analyses were on participants pooled from protocols MK-0431A-170 and -289, pooled by receipt of drug or placebo.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Percentage of Participants Initiating Insulin Glargine During Weeks 20-54 | 22.7 Percentage of participants |
| Metformin and Metformin XR Pooled | Percentage of Participants Initiating Insulin Glargine During Weeks 20-54 | 26.6 Percentage of participants |
Secondary
Percentage of Participants With A1C at Goal (<6.5%) at Week 20
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (\<6.5%) at Week 20 was presented.
Time frame: Week 20
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 | 29.0 Percentage of participants |
| Metformin and Metformin XR Pooled | Percentage of Participants With A1C at Goal (<6.5%) at Week 20 | 20.4 Percentage of participants |
Comparison: The percentage of participants with A1C at the A1C goal (\<6.5%) in the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled. For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method was used to impute whether the participant had met the goal.p-value: 0.04995% CI: [0, 24.8]Miettinen and Nurminen
Secondary
Percentage of Participants With A1C at Goal (<6.5%) at Week 54
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (\<6.5%) at Week 54 was presented.
Time frame: Week 54
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Percentage of Participants With A1C at Goal (<6.5%) at Week 54 | 18.6 Percentage of participants |
| Metformin and Metformin XR Pooled | Percentage of Participants With A1C at Goal (<6.5%) at Week 54 | 19.5 Percentage of participants |
Secondary
Percentage of Participants With A1C at Goal (<7.0%) at Week 20
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (\<7.0%) at Week 20 was presented.
Time frame: Week 20
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 | 43.0 Percentage of participants |
| Metformin and Metformin XR Pooled | Percentage of Participants With A1C at Goal (<7.0%) at Week 20 | 31.0 Percentage of participants |
Comparison: The percentage of participants with A1C at the A1C goal (\<7.0%) in the arm Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled is compared against that of Metformin and Metformin XR Pooled. For estimating the treatment difference, when the A1C result for a participant at Week 20 was not available, a multiple imputation method was used to impute whether the participant had met the goal.p-value: 0.01795% CI: [2.9, 28.9]Miettinen and Nurminen
Secondary
Percentage of Participants With A1C at Goal (<7.0%) at Week 54
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100. Percentage of participants with A1C at goal (\<7.0%) at Week 54 was presented.
Time frame: Week 54
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20. As defined in the protocols, these analyses were conducted in participants pooled from protocols MK-0431A-170 and MK-0431A-289, pooled according to receipt of experimental drug or placebo comparator.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Percentage of Participants With A1C at Goal (<7.0%) at Week 54 | 31.4 Percentage of participants |
| Metformin and Metformin XR Pooled | Percentage of Participants With A1C at Goal (<7.0%) at Week 54 | 27.3 Percentage of participants |
Other Pre-specified
Baseline A1C
Glycated hemoglobin (A1C) is a blood marker used to report average blood glucose levels over prolonged periods of time. Percentage A1C is the ratio of glycated hemoglobin to total hemoglobin x 100.
Time frame: Baseline
Population: The analysis population includes all randomized participants who received ≥1 dose of study medication and had a baseline measurement of A1C. Baseline A1C data for non-pooled arms are listed in the Baseline Characteristics module.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled | Baseline A1C | 7.96 Percentage of glycated hemoglobin | Standard Deviation 1.11 |
| Metformin and Metformin XR Pooled | Baseline A1C | 8.06 Percentage of glycated hemoglobin | Standard Deviation 1.07 |