Trial Outcomes & Findings for A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266) (NCT NCT01678820)

NCT ID: NCT01678820

Last Updated: 2018-08-24

Results Overview

A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented below under secondary outcome measures.

• Recruitment status: TERMINATED
• Study phase: PHASE3
• Target enrollment: 299 participants
• Primary outcome timeframe: Baseline and Week 16
• Results posted on: 2018-08-24

Participant Flow

All participants randomized population.

Participant milestones

Measure	Sitagliptin/Simvastatin FDC Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Overall Study STARTED	100	99	100
Overall Study Treated With Double-blind Study Drug	100	97	98
Overall Study COMPLETED	38	36	43
Overall Study NOT COMPLETED	62	63	57

Reasons for withdrawal

Measure	Sitagliptin/Simvastatin FDC Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Overall Study Study Terminated by Sponsor	45	43	43
Overall Study Withdrawal by Subject	2	5	2
Overall Study Protocol Specified Criteria	2	3	1
Overall Study Adverse Event	2	2	2
Overall Study Lost to Follow-up	7	2	2
Overall Study Non-compliance with study drug	0	1	0
Overall Study Physician Decision	0	0	1
Overall Study Protocol Violation	4	5	4
Overall Study Not treated with double-blind study drug	0	2	2

Baseline Characteristics

A Study of the Efficacy and Safety of MK-0431D (a Fixed-dose Combination of Sitagliptin and Simvastatin) for the Treatment of Participants With Type 2 Diabetes Mellitus (T2DM) With Inadequate Glycemic Control on Metformin Monotherapy (MK-0431D-266)

Baseline characteristics by cohort

Measure	Simvastatin n=100 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=99 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Total n=299 Participants Total of all reporting groups
Age, Continuous	54.9 Years STANDARD_DEVIATION 10.0 • n=5 Participants	54.9 Years STANDARD_DEVIATION 10.2 • n=5 Participants	54.2 Years STANDARD_DEVIATION 10.3 • n=7 Participants	54.7 Years STANDARD_DEVIATION 10.1 • n=4 Participants
Sex: Female, Male Female	49 Participants n=5 Participants	45 Participants n=5 Participants	52 Participants n=7 Participants	146 Participants n=4 Participants
Sex: Female, Male Male	51 Participants n=5 Participants	55 Participants n=5 Participants	47 Participants n=7 Participants	153 Participants n=4 Participants
Hemoglobin A1c (A1C)	8.22 Percent STANDARD_DEVIATION 1.19 • n=5 Participants	8.16 Percent STANDARD_DEVIATION 0.94 • n=5 Participants	8.15 Percent STANDARD_DEVIATION 1.09 • n=7 Participants	8.18 Percent STANDARD_DEVIATION 1.08 • n=4 Participants
Fasting plasma glucose (FPG)	175.7 mg/dL STANDARD_DEVIATION 49.3 • n=5 Participants	169.9 mg/dL STANDARD_DEVIATION 42.3 • n=5 Participants	175.9 mg/dL STANDARD_DEVIATION 48.6 • n=7 Participants	173.8 mg/dL STANDARD_DEVIATION 46.8 • n=4 Participants
Low-density lipoprotein cholesterol (LDL-C)	100.9 mg/dL STANDARD_DEVIATION 22.0 • n=5 Participants	106.5 mg/dL STANDARD_DEVIATION 26.7 • n=5 Participants	103.9 mg/dL STANDARD_DEVIATION 24.2 • n=7 Participants	103.7 mg/dL STANDARD_DEVIATION 24.4 • n=4 Participants
Total cholesterol (TC)	183.5 mg/dL STANDARD_DEVIATION 28.4 • n=5 Participants	189.3 mg/dL STANDARD_DEVIATION 30.9 • n=5 Participants	187.7 mg/dL STANDARD_DEVIATION 29.6 • n=7 Participants	186.8 mg/dL STANDARD_DEVIATION 29.6 • n=4 Participants
Apolipoprotein B (Apo B)	94.1 mg/dL STANDARD_DEVIATION 17.2 • n=5 Participants	97.8 mg/dL STANDARD_DEVIATION 19.0 • n=5 Participants	95.4 mg/dL STANDARD_DEVIATION 19.0 • n=7 Participants	95.8 mg/dL STANDARD_DEVIATION 18.4 • n=4 Participants
Non high-density lipoprotein cholesterol (non-HDL-C)	136.5 mg/dL STANDARD_DEVIATION 27.1 • n=5 Participants	141.7 mg/dL STANDARD_DEVIATION 30.9 • n=5 Participants	139.5 mg/dL STANDARD_DEVIATION 29.9 • n=7 Participants	139.2 mg/dL STANDARD_DEVIATION 29.3 • n=4 Participants
Triglycerides (TG)	184.2 mg/dL STANDARD_DEVIATION 118.6 • n=5 Participants	177.4 mg/dL STANDARD_DEVIATION 101.2 • n=5 Participants	180.8 mg/dL STANDARD_DEVIATION 119.1 • n=7 Participants	180.8 mg/dL STANDARD_DEVIATION 112.9 • n=4 Participants
High-density lipoprotein cholesterol (HDL-C)	47.0 mg/dL STANDARD_DEVIATION 11.2 • n=5 Participants	47.6 mg/dL STANDARD_DEVIATION 11.3 • n=5 Participants	48.2 mg/dL STANDARD_DEVIATION 12.1 • n=7 Participants	47.6 mg/dL STANDARD_DEVIATION 11.5 • n=4 Participants
Very low-density lipoprotein cholesterol (VLDL-C)	35.7 mg/dL STANDARD_DEVIATION 18.8 • n=5 Participants	35.4 mg/dL STANDARD_DEVIATION 18.8 • n=5 Participants	35.8 mg/dL STANDARD_DEVIATION 20.4 • n=7 Participants	35.6 mg/dL STANDARD_DEVIATION 19.3 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline and Week 16

Population: Full analysis set (FAS) population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. sitagliptin. Results for simvastatin are presented below under secondary outcome measures.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Change From Baseline in Hemoglobin A1C (A1C) at Week 16 (Sitagliptin/Simvastatin FDC vs. Sitagliptin)	-0.41 Percent Interval -0.64 to -0.17	-0.59 Percent Interval -0.83 to -0.36	—

PRIMARY outcome

Timeframe: Up to 16 weeks for non-serious AEs, up to 18 weeks for serious AEs

Population: All participants as treated population defined as all randomized participants who received at least one dose of study drug.

Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Number of Participants Who Experienced at Least One Adverse Event (AE)	13 Participants	13 Participants	17 Participants

PRIMARY outcome

Timeframe: Up to 16 weeks

Population: All participants as treated population defined as all randomized participants who received at least one dose of study drug.

Excludes data after rescue therapy. Adverse event is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Number of Participants Who Discontinued Study Drug Due to an Adverse Event	2 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

A1C is measured as percent. Thus, this change from baseline reflects the Week 16 A1C percent minus the Week 0 A1C percent. This primary outcome measure only includes results for sitagliptin/simvastatin FDC vs. simvastatin. Results for sitagliptin are presented above under primary outcome measures.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=98 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Change From Baseline in A1C at Week 16 (Sitagliptin/Simvastatin FDC vs. Simvastatin)	-0.41 Percent Interval -0.64 to -0.17	0.21 Percent Interval -0.02 to 0.45	—

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and who had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Change from baseline reflects the Week 16 value minus the Week 0 value.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Change From Baseline in Fasting Plasma Glucose (FPG) at Week 16	-7.9 mg/dL Interval -21.0 to 5.2	-9.6 mg/dL Interval -23.4 to 4.1	21.3 mg/dL Interval 7.9 to 34.7

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Percent Change From Baseline in Low-density Lipoprotein Cholesterol (LDL-C) at Week 16	-21.6 Percent change Interval -32.3 to -10.8	4.0 Percent change Interval -6.9 to 14.9	-26.9 Percent change Interval -37.5 to -16.3

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Percent Change From Baseline in Total Cholesterol (TC) at Week 16	-18.4 Percent change Interval -26.6 to -10.2	-0.4 Percent change Interval -8.6 to 7.9	-18.4 Percent change Interval -26.4 to -10.4

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=94 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Percent Change From Baseline in Apolipoprotein B (Apo B) at Week 16	-16.9 Percent change Interval -27.0 to -6.8	3.3 Percent change Interval -7.1 to 13.7	-19.8 Percent change Interval -30.0 to -9.6

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=96 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Percent Change From Baseline in Non-high Density Lipoprotein Cholesterol (Non-HDL-C) at Week 16	-23.9 Percent change Interval -33.9 to -13.9	0.6 Percent change Interval -9.5 to 10.7	-24.2 Percent change Interval -34.0 to -14.4

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Percent Change From Baseline in Triglycerides (TG) at Week 16	-20.4 Percent change Interval -51.9 to 11.1	-4.9 Percent change Interval -39.5 to 29.7	-10.1 Percent change Interval -52.1 to 31.9

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Percent Change From Baseline in High-density Lipoprotein Cholesterol (HDL-C) at Week 16	2.5 Percent change Interval -2.7 to 7.8	2.0 Percent change Interval -3.3 to 7.4	2.1 Percent change Interval -3.0 to 7.3

SECONDARY outcome

Timeframe: Baseline and Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Percent change from baseline was calculated as the Week 16 value minus the Week 0 value, divided by the Week 0 value ×100%.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=96 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Percent Change From Baseline in Very Low-density Lipoprotein Cholesterol (VLDL-C) at Week 16	-17.5 Percent change Interval -33.8 to -1.2	12.9 Percent change Interval -4.2 to 29.9	-2.2 Percent change Interval -18.9 to 14.5

SECONDARY outcome

Timeframe: Week 16

Population: FAS population defined as all randomized participants who took at least one dose of study drug and had at least one measurement for the analysis of this outcome measure (baseline or subsequent to the first dose of study drug).

Percentage of participants achieving glycemic goal (A1C <7%) after 16 weeks of treatment. Data as observed.

Outcome measures

Measure	Sitagliptin/Simvastatin FDC n=100 Participants Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 Participants Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 Participants Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Percentage of Participants With A1C Level <7% at Week 16	29.9 Percentage of participants	29.6 Percentage of participants	17.6 Percentage of participants

Adverse Events

Sitagliptin/Simvastatin FDC

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Simvastatin

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Sitagliptin/Simvastatin FDC n=100 participants at risk Sitagliptin 100 mg/simvastatin 40 mg FDC plus placebo to sitagliptin plus placebo to simvastatin administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Sitagliptin n=97 participants at risk Sitagliptin 100 mg plus placebo to simvastatin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.	Simvastatin n=98 participants at risk Simvastatin 40 mg plus placebo to sitagliptin plus placebo to sitagliptin/simvastatin FDC administered orally once daily in the evening. Participants will continue on their stable pre-screening metformin dose and dosing regimen of \>=1500 mg daily for the duration of the study. Participants may receive glimepiride 1 mg once daily or 2 mg once daily (may be up-titrated to 6 mg once daily) as rescue therapy.
Gastrointestinal disorders Abdominal pain	1.0% 1/100 • Number of events 1 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.	0.00% 0/97 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.	0.00% 0/98 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.
Gastrointestinal disorders Intestinal obstruction	1.0% 1/100 • Number of events 1 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.	0.00% 0/97 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.	0.00% 0/98 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.
Musculoskeletal and connective tissue disorders Musculoskeletal chest pain	0.00% 0/100 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.	0.00% 0/97 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.	1.0% 1/98 • Number of events 1 • Up to 18 weeks All participants as treated population defined as all randomized participants who received at least one dose of study drug. Serious adverse events include data after rescue therapy and non-serious adverse events exclude data after rescue therapy.

Other adverse events

Adverse event data not reported

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: ClinicalTrialsDisclosure@merck.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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.
• Publication restrictions are in place

Restriction type: OTHER