A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Participants With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin) (MK-0431A-170/MK-0431A-289)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01760447
• Collaborator: (none)
• Enrollment: 223
• Arms: 4
• Actual Duration (Months): 93.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 2 Diabetes Mellitus	Drug: Sitagliptin plus metformin; Drug: Placebo to metformin; Drug: Metformin; Drug: Placebo to sitagliptin plus metformin; Drug: Sitagliptin plus metformin XR; Drug: Placebo to metformin XR; Drug: Insulin; Drug: Placebo to sitagliptin plus metformin XR; Drug: Metformin XR	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 223 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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."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."
• Masking: Quadruple (Participant, Care Provider, 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.
• Primary Purpose: Treatment
• Official Title: A Pooled Analysis of the Safety and Efficacy of MK-0431A and MK-0431A XR in Pediatric Patients With Type 2 Diabetes Mellitus With Inadequate Glycemic Control on Metformin Therapy (Alone or in Combination With Insulin)
• Actual Study Start Date: Dec 7, 2011
• Actual Primary Completion Date: Sep 17, 2019
• Actual Study Completion Date: Sep 17, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Sitagliptin 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.; Other Names: MK-0431A ; Drug: Placebo to metformin; Participants received 2 tablets daily, one taken with a morning meal and one taken with an evening meal. Each tablet contained placebo to metformin.; Drug: Insulin; 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.
Placebo Comparator: 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.	Drug: 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 1000 mg, 1700 mg or 2000 mg of metformin. Dosage was based on each participant's daily metformin dose prior to enrollment.; Drug: Placebo 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.; Other Names: Placebo to MK-0431A ; Drug: Insulin; 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.
Experimental: 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.	Drug: Sitagliptin 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.; Other Names: MK-0431A XR ; Drug: Placebo to metformin XR; Participants received 2 tablets daily, both taken together with a meal. Each tablet contained placebo to metformin XR.; Drug: Insulin; 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.
Placebo Comparator: 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.	Drug: Insulin; 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.; Drug: Placebo 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.; Other Names: Placebo to MK-0431A XR ; Drug: Metformin 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.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

Secondary Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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.

7. 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.

8. 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.

9. 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.

Other Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 10 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 3, 2018

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01760447
• Other Study ID Numbers: 0431A-289; 2012-004035-23; 2011-002529-23; 2014-003583-20; MK-0431A-170; MK-0431A-289; CTRI/2012/09/003025; NCT01472367
• First Posted: Jan 4, 2013
• Last Update Posted: Nov 16, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Metformin; Sitagliptin Phosphate

Study Results

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 Detail	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.

Arm/Group Title	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR
Arm/Group Description	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.	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.	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.	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.
Period Title: Weeks 0-20
STARTED	62	62	47	51
Treated	62	62	45	51
COMPLETED	59	62	42	47
NOT COMPLETED	3	0	5	4
Period Title: Weeks 0-20
STARTED	28	30	42	47
COMPLETED	25	28	39	43
NOT COMPLETED	3	2	3	4

Baseline Characteristics

Arm/Group Title	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Total
Arm/Group Description	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.	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.	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.	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.	Total of all reporting groups
Overall Participants	62	62	45	51	220
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.4 (2.2)	13.9 (1.8)	14.8 (1.9)	14.9 (1.6)	14.4 (1.9)
Age, Customized (Count of Participants)
In utero	0 0%	0 0%	0 0%	0 0%	0 0%
Preterm newborn infants (gestational age < 37 wks)	0 0%	0 0%	0 0%	0 0%	0 0%
Newborns (0-27 days)	0 0%	0 0%	0 0%	0 0%	0 0%
Infants and toddlers (28 days-23 months)	0 0%	0 0%	0 0%	0 0%	0 0%
Children (2-11 years)	10 16.1%	7 11.3%	3 6.7%	1 2%	21 9.5%
Adolescents (12-17 years)	52 83.9%	55 88.7%	42 93.3%	50 98%	199 90.5%
Adults (18-64 years)	0 0%	0 0%	0 0%	0 0%	0 0%
From 65-84 years	0 0%	0 0%	0 0%	0 0%	0 0%
85 years and over	0 0%	0 0%	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	41 66.1%	40 64.5%	32 71.1%	32 62.7%	145 65.9%
Male	21 33.9%	22 35.5%	13 28.9%	19 37.3%	75 34.1%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	23 37.1%	23 37.1%	11 24.4%	20 39.2%	77 35%
Not Hispanic or Latino	35 56.5%	36 58.1%	29 64.4%	28 54.9%	128 58.2%
Unknown or Not Reported	4 6.5%	3 4.8%	5 11.1%	3 5.9%	15 6.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	1 1.6%	3 6.7%	9 17.6%	13 5.9%
Asian	21 33.9%	22 35.5%	15 33.3%	6 11.8%	64 29.1%
Native Hawaiian or Other Pacific Islander	1 1.6%	1 1.6%	0 0%	0 0%	2 0.9%
Black or African American	2 3.2%	2 3.2%	2 4.4%	4 7.8%	10 4.5%
White	24 38.7%	23 37.1%	22 48.9%	27 52.9%	96 43.6%
More than one race	14 22.6%	13 21%	3 6.7%	5 9.8%	35 15.9%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Glycated Hemoglobin (A1C) (Percentage) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage]	8.02 (1.22)	8.13 (1.08)	7.87 (0.94)	7.97 (1.05)	8.0 (1.1)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in A1C at Week 20
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	107	113
Least Squares Mean (95% Confidence Interval) [Percentage of glycated hemoglobin]	-0.58	-0.09

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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."
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.018
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-0.49
	Confidence Interval	(2-Sided) 95%; -0.90 to -0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-20
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who received ≥1 dose of study medication.

Arm/Group Title	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	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.	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.	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.	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.	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	62	62	45	51	107	113
Count of Participants [Participants]	42 67.7%	46 74.2%	29 64.4%	30 58.8%	71 32.3%	76 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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."
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; -13.9 to 11.3
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Miettinen and Nurminen methodology was used to calculate the difference and 95% confidence interval.

3. Primary Outcome

Title	Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-20
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who received ≥1 dose of study medication.

Arm/Group Title	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	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.	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.	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.	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.	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	62	62	45	51	107	113
Count of Participants [Participants]	1 1.6%	2 3.2%	2 4.4%	2 3.9%	3 1.4%	4 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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."
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; -6.2 to 5.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Miettinen and Nurminen methodology was used to calculate the difference and 95% confidence interval.

4. Primary Outcome

Title	Number of Participants Who Experienced ≥1 Adverse Event During Weeks 0-56
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20.

Arm/Group Title	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	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.	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.	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.	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.	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	28	30	42	47	70	77
Count of Participants [Participants]	26 41.9%	27 43.5%	36 80%	39 76.5%	62 28.2%	66 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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."
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; -8.9 to 14.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Miettinen and Nurminen methodology was used to calculate the difference and 95% confidence interval.

5. Primary Outcome

Title	Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event During Weeks 0-54
Description	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

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who received ≥1 dose of study medication and continued in the study beyond Week 20.

Arm/Group Title	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	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.	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.	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.	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.	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	28	30	42	47	70	77
Count of Participants [Participants]	1 1.6%	1 1.6%	1 2.2%	3 5.9%	2 0.9%	4 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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."
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	-2.1
	Confidence Interval	(2-Sided) 95%; -10.1 to 5.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Miettinen and Nurminen methodology was used to calculate the difference and 95% confidence interval.

6. Secondary Outcome

Title	Change From Baseline in A1C at Week 54
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	70	77
Least Squares Mean (95% Confidence Interval) [Percentage of glycated hemoglobin]	0.35	0.73

7. Secondary Outcome

Title	Change From Baseline in Fasting Plasma Glucose (FPG) at Week 20
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	107	113
Least Squares Mean (95% Confidence Interval) [mg/dL]	-2.5	8.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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."
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	= 0.159
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference
	Estimated Value	-10.8
	Confidence Interval	(2-Sided) 95%; -25.9 to 4.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change From Baseline in FPG at Week 54
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	70	77
Least Squares Mean (95% Confidence Interval) [mg/dL]	16.8	16.9

9. Secondary Outcome

Title	Percentage of Participants With A1C at Goal (<7.0%) at Week 20
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	107	113
Number [Percentage of participants]	43.0 69.4%	31.0 50%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.017
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	16.0
	Confidence Interval	(2-Sided) 95%; 2.9 to 28.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With A1C at Goal (<6.5%) at Week 20
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	107	113
Number [Percentage of participants]	29.0 46.8%	20.4 32.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.049
	Comments
	Method	Miettinen and Nurminen
	Comments
Method of Estimation	Estimation Parameter	Difference in Percentage
	Estimated Value	12.2
	Confidence Interval	(2-Sided) 95%; 0.0 to 24.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants With A1C at Goal (<7.0%) at Week 54
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	70	77
Number [Percentage of participants]	31.4 50.6%	27.3 44%

12. Secondary Outcome

Title	Percentage of Participants With A1C at Goal (<6.5%) at Week 54
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	70	77
Number [Percentage of participants]	18.6 30%	19.5 31.5%

13. Secondary Outcome

Title	Percentage of Participants Initiating Glycemic Rescue Therapy by Week 20
Description	Percentage of participants who initiated glycemic rescue therapy prior to Week 20 was reported.
Time Frame	Up to Week 20

Outcome Measure Data

Analysis Population Description

The analysis population includes all randomized participants who received ≥1 dose of study medication.

Arm/Group Title	Sitagliptin/Metformin	Metformin	Sitagliptin/Metformin XR	Metformin XR	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	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.	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.	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.	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.	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	62	62	45	51	107	113
Number [Percentage of participants]	3.2 5.2%	19.4 31.3%	4.4 9.8%	13.7 26.9%	3.7 1.7%	16.8 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled, Metformin and Metformin XR Pooled
	Comments	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."
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Log-Rank Test
	Comments
Method of Estimation	Estimation Parameter	Kaplan-Meier Difference in Percentage
	Estimated Value	-13.2
	Confidence Interval	(2-Sided) 95%; -21.1 to -5.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Percentage of Participants Initiating Insulin Glargine During Weeks 20-54
Description	Percentage of participants who initiated insulin glargine therapy from Weeks 20 through 54 was reported.
Time Frame	Week 20 up to Week 54

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	66	64
Number [Percentage of participants]	22.7 36.6%	26.6 42.9%

15. Other Pre-specified Outcome

Title	Baseline A1C
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	Metformin and Metformin XR Pooled
Arm/Group Description	This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).	This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
Measure Participants	107	113
Mean (Standard Deviation) [Percentage of glycated hemoglobin]	7.96 (1.11)	8.06 (1.07)

Adverse Events

Time Frame	Up to 56 weeks for non-serious adverse events. Up to approximately 76 weeks for serious adverse events. Up to approximately 78 weeks for all-cause mortality.
Adverse Event Reporting Description	"Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled" = "Sitagliptin/Metformin" plus "Sitagliptin/Metformin XR." "Metformin and Metformin XR Pooled" = "Metformin" plus "Metformin XR." Non-serious and serious adverse events are recorded for all treated participants. All-cause mortality is recorded for all randomized participants.
Arm/Group Title	Sitagliptin/Metformin		Metformin		Sitagliptin/Metformin XR		Metformin XR		Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled		Metformin and Metformin XR Pooled
Arm/Group Description	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.		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.		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.		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.		This reporting group contains the pooled population of treated participants from the experimental-drug groups "Sitagliptin/Metformin" (from protocol MK-0431A-170) and "Sitagliptin/Metformin XR" (from protocol MK-0431A-289).		This reporting group contains the pooled population of treated participants from the placebo groups "Metformin" (from protocol MK-0431A-170) and "Metformin XR" (from protocol MK-0431A-289).
All Cause Mortality
	Sitagliptin/Metformin		Metformin		Sitagliptin/Metformin XR		Metformin XR		Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled		Metformin and Metformin XR Pooled
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/62 (1.6%)		0/62 (0%)		0/47 (0%)		0/51 (0%)		1/109 (0.9%)		0/113 (0%)
Serious Adverse Events
	Sitagliptin/Metformin		Metformin		Sitagliptin/Metformin XR		Metformin XR		Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled		Metformin and Metformin XR Pooled
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/62 (6.5%)		3/62 (4.8%)		3/45 (6.7%)		3/51 (5.9%)		7/107 (6.5%)		6/113 (5.3%)
Gastrointestinal disorders
Abdominal pain upper	0/62 (0%)	0	0/62 (0%)	0	0/45 (0%)	0	1/51 (2%)	1	0/107 (0%)	0	1/113 (0.9%)	1
Diarrhoea	0/62 (0%)	0	0/62 (0%)	0	1/45 (2.2%)	1	0/51 (0%)	0	1/107 (0.9%)	1	0/113 (0%)	0
Vomiting	0/62 (0%)	0	0/62 (0%)	0	0/45 (0%)	0	1/51 (2%)	1	0/107 (0%)	0	1/113 (0.9%)	1
General disorders
Death	1/62 (1.6%)	1	0/62 (0%)	0	0/45 (0%)	0	0/51 (0%)	0	1/107 (0.9%)	1	0/113 (0%)	0
Immune system disorders
Type I hypersensitivity	1/62 (1.6%)	1	0/62 (0%)	0	0/45 (0%)	0	0/51 (0%)	0	1/107 (0.9%)	1	0/113 (0%)	0
Infections and infestations
Gastroenteritis	0/62 (0%)	0	0/62 (0%)	0	1/45 (2.2%)	1	0/51 (0%)	0	1/107 (0.9%)	1	0/113 (0%)	0
H1N1 influenza	0/62 (0%)	0	0/62 (0%)	0	0/45 (0%)	0	1/51 (2%)	1	0/107 (0%)	0	1/113 (0.9%)	1
Pyelonephritis	1/62 (1.6%)	1	0/62 (0%)	0	0/45 (0%)	0	0/51 (0%)	0	1/107 (0.9%)	1	0/113 (0%)	0
Upper respiratory tract infection	0/62 (0%)	0	0/62 (0%)	0	1/45 (2.2%)	1	0/51 (0%)	0	1/107 (0.9%)	1	0/113 (0%)	0
Investigations
Blood glucose increased	0/62 (0%)	0	1/62 (1.6%)	1	0/45 (0%)	0	0/51 (0%)	0	0/107 (0%)	0	1/113 (0.9%)	1
Metabolism and nutrition disorders
Hyperglycaemia	0/62 (0%)	0	1/62 (1.6%)	1	0/45 (0%)	0	1/51 (2%)	1	0/107 (0%)	0	2/113 (1.8%)	2
Musculoskeletal and connective tissue disorders
Synovial cyst	1/62 (1.6%)	1	0/62 (0%)	0	0/45 (0%)	0	0/51 (0%)	0	1/107 (0.9%)	1	0/113 (0%)	0
Nervous system disorders
Epilepsy	0/62 (0%)	0	1/62 (1.6%)	1	0/45 (0%)	0	0/51 (0%)	0	0/107 (0%)	0	1/113 (0.9%)	1
Psychiatric disorders
Suicide attempt	0/62 (0%)	0	0/62 (0%)	0	0/45 (0%)	0	1/51 (2%)	1	0/107 (0%)	0	1/113 (0.9%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	1/62 (1.6%)	1	0/62 (0%)	0	0/45 (0%)	0	0/51 (0%)	0	1/107 (0.9%)	1	0/113 (0%)	0
Other (Not Including Serious) Adverse Events
	Sitagliptin/Metformin		Metformin		Sitagliptin/Metformin XR		Metformin XR		Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled		Metformin and Metformin XR Pooled
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	34/62 (54.8%)		40/62 (64.5%)		30/45 (66.7%)		36/51 (70.6%)		64/107 (59.8%)		76/113 (67.3%)
Gastrointestinal disorders
Abdominal pain	2/62 (3.2%)	2	4/62 (6.5%)	4	4/45 (8.9%)	4	4/51 (7.8%)	4	6/107 (5.6%)	6	8/113 (7.1%)	8
Abdominal pain upper	1/62 (1.6%)	2	2/62 (3.2%)	2	0/45 (0%)	0	3/51 (5.9%)	4	1/107 (0.9%)	2	5/113 (4.4%)	6
Diarrhoea	7/62 (11.3%)	8	4/62 (6.5%)	4	1/45 (2.2%)	1	3/51 (5.9%)	10	8/107 (7.5%)	9	7/113 (6.2%)	14
Nausea	2/62 (3.2%)	5	5/62 (8.1%)	5	4/45 (8.9%)	6	2/51 (3.9%)	3	6/107 (5.6%)	11	7/113 (6.2%)	8
Infections and infestations
Gastroenteritis	5/62 (8.1%)	6	3/62 (4.8%)	3	3/45 (6.7%)	3	2/51 (3.9%)	2	8/107 (7.5%)	9	5/113 (4.4%)	5
Influenza	1/62 (1.6%)	1	4/62 (6.5%)	5	2/45 (4.4%)	3	3/51 (5.9%)	5	3/107 (2.8%)	4	7/113 (6.2%)	10
Nasopharyngitis	7/62 (11.3%)	11	7/62 (11.3%)	7	1/45 (2.2%)	2	2/51 (3.9%)	3	8/107 (7.5%)	13	9/113 (8%)	10
Pharyngitis	1/62 (1.6%)	1	3/62 (4.8%)	3	1/45 (2.2%)	1	5/51 (9.8%)	6	2/107 (1.9%)	2	8/113 (7.1%)	9
Upper respiratory tract infection	9/62 (14.5%)	11	6/62 (9.7%)	8	5/45 (11.1%)	9	3/51 (5.9%)	5	14/107 (13.1%)	20	9/113 (8%)	13
Urinary tract infection	0/62 (0%)	0	5/62 (8.1%)	6	3/45 (6.7%)	3	1/51 (2%)	1	3/107 (2.8%)	3	6/113 (5.3%)	7
Investigations
Alanine aminotransferase increased	2/62 (3.2%)	3	3/62 (4.8%)	3	3/45 (6.7%)	3	3/51 (5.9%)	3	5/107 (4.7%)	6	6/113 (5.3%)	6
Blood creatine phosphokinase increased	3/62 (4.8%)	3	1/62 (1.6%)	1	3/45 (6.7%)	3	1/51 (2%)	1	6/107 (5.6%)	6	2/113 (1.8%)	2
Blood glucose increased	3/62 (4.8%)	4	0/62 (0%)	0	2/45 (4.4%)	2	3/51 (5.9%)	5	5/107 (4.7%)	6	3/113 (2.7%)	5
Creatinine renal clearance increased	4/62 (6.5%)	4	0/62 (0%)	0	0/45 (0%)	0	0/51 (0%)	0	4/107 (3.7%)	4	0/113 (0%)	0
Urine albumin/creatinine ratio increased	4/62 (6.5%)	5	2/62 (3.2%)	2	0/45 (0%)	0	0/51 (0%)	0	4/107 (3.7%)	5	2/113 (1.8%)	2
Metabolism and nutrition disorders
Hyperglycaemia	3/62 (4.8%)	3	5/62 (8.1%)	6	3/45 (6.7%)	3	4/51 (7.8%)	4	6/107 (5.6%)	6	9/113 (8%)	10
Hypoglycaemia	10/62 (16.1%)	106	6/62 (9.7%)	15	9/45 (20%)	70	10/51 (19.6%)	45	19/107 (17.8%)	176	16/113 (14.2%)	60
Nervous system disorders
Headache	3/62 (4.8%)	4	8/62 (12.9%)	10	2/45 (4.4%)	4	10/51 (19.6%)	15	5/107 (4.7%)	8	18/113 (15.9%)	25
Respiratory, thoracic and mediastinal disorders
Cough	2/62 (3.2%)	2	3/62 (4.8%)	4	3/45 (6.7%)	3	2/51 (3.9%)	2	5/107 (4.7%)	5	5/113 (4.4%)	6
Oropharyngeal pain	2/62 (3.2%)	2	1/62 (1.6%)	1	3/45 (6.7%)	3	1/51 (2%)	6	5/107 (4.7%)	5	2/113 (1.8%)	7

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission. Sponsor review can be expedited to meet publication timelines.