A Pooled Analysis of the Safety and Efficacy of MK-0431A... | NCT01760447

NCT01760447

ID	Type	Description
2012-004035-23	EudraCT Number
2011-002529-23	EudraCT Number
2014-003583-20	EudraCT Number
MK-0431A-170	Other Identifier	Merck Protocol Number
MK-0431A-289	Other Identifier	Merck Protocol Number
CTRI/2012/09/003025	Registry Identifier	CTRI

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Sitagliptin/Metformin	Experimental	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 Drug: Placebo to metformin Drug: Insulin
Metformin	Placebo Comparator	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 Drug: Placebo to sitagliptin plus metformin Drug: Insulin
Sitagliptin/Metformin XR	Experimental	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 Drug: Placebo to metformin XR Drug: Insulin
Metformin XR	Placebo Comparator	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.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Sitagliptin plus metformin	Drug	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Baseline and Week 20
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.	Up to Week 20
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.	Up to Week 20
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.	Up to approximately Week 56
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.

Secondary Outcomes

Measure	Description	Time Frame
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.	Baseline and Week 54

Other Outcomes

Measure	Description	Time Frame
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.	Baseline

Eligibility Module

Eligibility Criteria

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

Name	Affiliation	Role
Medical Director	Merck Sharp & Dohme LLC	Study Director

PubMed Identifier	Type	Citation	Retractions
34779103	Derived	Jalaludin MY, Deeb A, Zeitler P, Garcia R, Newfield RS, Samoilova Y, Rosario CA, Shehadeh N, Saha CK, Zhang Y, Zilli M, Scherer LW, Lam RLH, Golm GT, Engel SS, Kaufman KD, Shankar RR. Efficacy and safety of the addition of sitagliptin to treatment of youth with type 2 diabetes and inadequate glycemic control on metformin without or with insulin. Pediatr Diabetes. 2022 Mar;23(2):183-193. doi: 10.1111/pedi.13282. Epub 2021 Dec 20.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Apr 3, 2018

Arm/Group Information

ID	Title	Description
BG000	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.
BG001	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.
BG002	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.
BG003	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.
BG004	Total	Total of all reporting groups

Units	Counts
Participants	BG00062 BG00162 BG00245 BG00351 BG004220

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00014.4± 2.2 BG00113.9± 1.8 BG00214.8± 1.9 BG003

Age, Customized

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
In utero	BG0000 BG0010 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00041 BG00140 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG00023 BG00123 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Glycated Hemoglobin (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.

Mean

Standard Deviation

Percentage

Title

Denominators

Categories

Title	Measurements
	BG0008.02± 1.22 BG001

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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.

Posted

Least Squares Mean

95% Confidence Interval

Percentage of glycated hemoglobin

Baseline and Week 20

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

Units	Counts
Participants	OG000107 OG001113

Title

Denominators

Categories

Title	Measurements
	OG000-0.58(-0.94 to -0.22) OG001-0.09(-0.43 to 0.26)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001	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."	Mixed Models Analysis		= 0.018		Least Squares Mean Difference	-0.49			2-Sided	95	-0.90	-0.09					Superiority

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.

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

Posted

Count of Participants

Participants

Up to Week 20

ID	Title	Description
OG000	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.
OG001	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.
OG002	Sitagliptin/Metformin XR

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.

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

Posted

Count of Participants

Participants

Up to Week 20

ID	Title	Description
OG000	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.
OG001	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.
OG002

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.

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

Posted

Count of Participants

Participants

Up to approximately Week 56

ID	Title	Description
OG000	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.
OG001	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.
OG002

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.

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

Posted

Count of Participants

Participants

Up to Week 54

ID	Title	Description
OG000	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.
OG001	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.

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.

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.

Posted

Least Squares Mean

95% Confidence Interval

Percentage of glycated hemoglobin

Baseline and Week 54

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

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.

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.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 20

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

Units	Counts

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.

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.

Posted

Least Squares Mean

95% Confidence Interval

mg/dL

Baseline and Week 54

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

Units	Counts

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.

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.

Posted

Number

Percentage of participants

Week 20

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

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.

Posted

Number

Percentage of participants

Week 20

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

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.

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.

Posted

Number

Percentage of participants

Week 54

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

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.

Posted

Number

Percentage of participants

Week 54

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

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.

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

Posted

Number

Percentage of participants

Up to Week 20

ID	Title	Description
OG000	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.
OG001	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.
OG002	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.

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.

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.

Posted

Number

Percentage of participants

Week 20 up to Week 54

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

Units	Counts

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.

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.

Posted

Mean

Standard Deviation

Percentage of glycated hemoglobin

Baseline

ID	Title	Description
OG000	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).
OG001	Metformin and Metformin XR Pooled	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).

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	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.	1	62	4	62	34	62
EG001	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.	0	62	3	62	40	62
EG002	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.	0	47	3	45	30	45
EG003	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.	0	51	3	51	36	51
EG004	Sitagliptin/Metformin and Sitagliptin/Metformin XR Pooled	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).	1	109	7	107	64	107
EG005	Metformin and Metformin XR Pooled	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).	0	113	6	113	76	113

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG0031 events1 affected51 at risk EG0040 events0 affected107 at risk EG0051 events1 affected113 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected62 at risk EG0021 events1 affected45 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003
Type I hypersensitivity	Immune system disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected62 at risk EG0021 events1 affected45 at risk EG003
H1N1 influenza	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003
Pyelonephritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected62 at risk EG0021 events1 affected45 at risk EG003
Blood glucose increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected62 at risk EG0020 events0 affected45 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected62 at risk EG0020 events0 affected45 at risk EG003
Synovial cyst	Musculoskeletal and connective tissue disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003
Epilepsy	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0011 events1 affected62 at risk EG0020 events0 affected45 at risk EG003
Suicide attempt	Psychiatric disorders	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003
Asthma	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003
Death	General disorders	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected62 at risk EG0014 events4 affected62 at risk EG0024 events4 affected45 at risk EG0034 events4 affected51 at risk EG0046 events6 affected107 at risk EG0058 events8 affected113 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events1 affected62 at risk EG0012 events2 affected62 at risk EG0020 events0 affected45 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0008 events7 affected62 at risk EG0014 events4 affected62 at risk EG0021 events1 affected45 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 22.0	Systematic Assessment	EG0005 events2 affected62 at risk EG0015 events5 affected62 at risk EG0026 events4 affected45 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0006 events5 affected62 at risk EG0013 events3 affected62 at risk EG0023 events3 affected45 at risk EG003
Influenza	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected62 at risk EG0015 events4 affected62 at risk EG0023 events2 affected45 at risk EG003
Nasopharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG00011 events7 affected62 at risk EG0017 events7 affected62 at risk EG0022 events1 affected45 at risk EG003
Pharyngitis	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0001 events1 affected62 at risk EG0013 events3 affected62 at risk EG0021 events1 affected45 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG00011 events9 affected62 at risk EG0018 events6 affected62 at risk EG0029 events5 affected45 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 22.0	Systematic Assessment	EG0000 events0 affected62 at risk EG0016 events5 affected62 at risk EG0023 events3 affected45 at risk EG003
Alanine aminotransferase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0003 events2 affected62 at risk EG0013 events3 affected62 at risk EG0023 events3 affected45 at risk EG003
Blood creatine phosphokinase increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0003 events3 affected62 at risk EG0011 events1 affected62 at risk EG0023 events3 affected45 at risk EG003
Blood glucose increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0004 events3 affected62 at risk EG0010 events0 affected62 at risk EG0022 events2 affected45 at risk EG003
Creatinine renal clearance increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0004 events4 affected62 at risk EG0010 events0 affected62 at risk EG0020 events0 affected45 at risk EG003
Urine albumin/creatinine ratio increased	Investigations	MedDRA 22.0	Systematic Assessment	EG0005 events4 affected62 at risk EG0012 events2 affected62 at risk EG0020 events0 affected45 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG0003 events3 affected62 at risk EG0016 events5 affected62 at risk EG0023 events3 affected45 at risk EG003
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 22.0	Systematic Assessment	EG000106 events10 affected62 at risk EG00115 events6 affected62 at risk EG00270 events9 affected45 at risk EG003
Headache	Nervous system disorders	MedDRA 22.0	Systematic Assessment	EG0004 events3 affected62 at risk EG00110 events8 affected62 at risk EG0024 events2 affected45 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected62 at risk EG0014 events3 affected62 at risk EG0023 events3 affected45 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 22.0	Systematic Assessment	EG0002 events2 affected62 at risk EG0011 events1 affected62 at risk EG0023 events3 affected45 at risk EG003

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D011719	Pyrazines
D001645	Biguanides
D006146	Guanidines
D000578	Amidines
D009930	Organic Chemicals
D011384	Proinsulin
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins

ID	Term
D000068900	Sitagliptin Phosphate
D008687	Metformin
D007328	Insulin