Trial Outcomes & Findings for Comparison of Two Treatment Regimens (Sitagliptin Versus Liraglutide) on Participants Who Failed to Achieve Good Glucose Control on Metformin Alone (MK-0431-403) (NCT NCT01296412)

Last Updated: 2017-06-09

Results Overview

A1C is measured as percent. Thus, this change from baseline reflects the Week 26 A1C percent minus the Week 0 A1C percent.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

653 participants

Primary outcome timeframe

Baseline and Week 26

Results posted on

2017-06-09

Participant Flow

Participant milestones

Participant milestones
Measure	Sitagliptin +/- Glimepiride Sitagliptin 100 mg tablet once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride for glycemic control.	Liraglutide Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.
Overall Study STARTED	326	327
Overall Study COMPLETED	275	257
Overall Study NOT COMPLETED	51	70

Reasons for withdrawal

Reasons for withdrawal
Measure	Sitagliptin +/- Glimepiride Sitagliptin 100 mg tablet once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride for glycemic control.	Liraglutide Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.
Overall Study Adverse Event	8	29
Overall Study Lack of Efficacy	1	0
Overall Study Lost to Follow-up	10	7
Overall Study Non-compliance with study drug	1	2
Overall Study Other reason not specified	20	15
Overall Study Physician Decision	1	3
Overall Study Pregnancy	0	1
Overall Study Withdrawal by Subject	10	13

Baseline Characteristics

Comparison of Two Treatment Regimens (Sitagliptin Versus Liraglutide) on Participants Who Failed to Achieve Good Glucose Control on Metformin Alone (MK-0431-403)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Sitagliptin +/- Glimepiride n=326 Participants Sitagliptin 100 mg tablet once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride for glycemic control.	Liraglutide n=327 Participants Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.	Total n=653 Participants Total of all reporting groups
Age, Continuous	56.9 years STANDARD_DEVIATION 10.0 • n=5 Participants	57.6 years STANDARD_DEVIATION 10.8 • n=7 Participants	57.3 years STANDARD_DEVIATION 10.4 • n=5 Participants
Sex: Female, Male Female	148 Participants n=5 Participants	147 Participants n=7 Participants	295 Participants n=5 Participants
Sex: Female, Male Male	178 Participants n=5 Participants	180 Participants n=7 Participants	358 Participants n=5 Participants
Hemoglobin A1c (A1C)	8.2 Percent STANDARD_DEVIATION 1.1 • n=5 Participants	8.1 Percent STANDARD_DEVIATION 0.9 • n=7 Participants	8.2 Percent STANDARD_DEVIATION 1.0 • n=5 Participants
Fasting Plasma Glucose	174.1 mg/dL STANDARD_DEVIATION 43.7 • n=5 Participants	172.9 mg/dL STANDARD_DEVIATION 40.8 • n=7 Participants	173.5 mg/dL STANDARD_DEVIATION 42.3 • n=5 Participants

PRIMARY outcome

Timeframe: Baseline and Week 26

Population: Per-protocol population defined as participants who had a measurement at baseline and a measurement after at least 24 weeks (i.e., 168 days) of treatment, and did not have any major protocol violations.

A1C is measured as percent. Thus, this change from baseline reflects the Week 26 A1C percent minus the Week 0 A1C percent.

Outcome measures

Outcome measures
Measure	Sitagliptin +/- Glimepiride n=269 Participants Sitagliptin 100 mg tablet once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride for glycemic control.	Liraglutide n=253 Participants Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.
Change From Baseline in Hemoglobin A1c (A1C)	-1.32 percent 95% Confidence Interval 1.06 • Interval -1.42 to -1.23	-1.42 percent 95% Confidence Interval 1.04 • Interval -1.51 to -1.32

SECONDARY outcome

Timeframe: Baseline and Week 26

Change from baseline at Week 26 is defined as Week 26 minus Week 0.

Outcome measures

Outcome measures
Measure	Sitagliptin +/- Glimepiride n=269 Participants Sitagliptin 100 mg tablet once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride for glycemic control.	Liraglutide n=252 Participants Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.
Change From Baseline in Fasting Plasma Glucose (FPG)	-33.7 mg/dL 95% Confidence Interval 46.2 • Interval -37.5 to -29.9	-39.6 mg/dL 95% Confidence Interval 40.3 • Interval -43.6 to -35.7

SECONDARY outcome

Timeframe: Week 26

Outcome measures

Outcome measures
Measure	Sitagliptin +/- Glimepiride n=269 Participants Sitagliptin 100 mg tablet once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride for glycemic control.	Liraglutide n=253 Participants Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.
Percentage of Participants Reaching A1C Goal of <7.0%	62.8 percentage of participants	72.3 percentage of participants

SECONDARY outcome

Timeframe: Week 26

Outcome measures

Outcome measures
Measure	Sitagliptin +/- Glimepiride n=269 Participants Sitagliptin 100 mg tablet once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride for glycemic control.	Liraglutide n=253 Participants Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.
Percentage of Participants Reaching A1C Goal of <6.5%	33.8 percentage of participants	38.3 percentage of participants

Adverse Events

Sitagliptin +/- Glimepiride

Serious events: 17 serious events

Other events: 58 other events

Deaths: 0 deaths

Liraglutide

Serious events: 12 serious events

Other events: 97 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Sitagliptin +/- Glimepiride n=326 participants at risk Sitagliptin 100 mg tablet once daily for 26 weeks. Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have received glimepiride for glycemic control.	Liraglutide n=324 participants at risk Liraglutide subcutaneous injection once daily for 26 weeks (starting dose 0.6 mg daily up-titrated to 1.2 mg daily on Day 8). Participants continued their stable dose of metformin \>=1500 mg orally daily. Participants may have had their liraglutide dose uptitrated to 1.8 mg daily for glycemic control.
Gastrointestinal disorders Diarrhoea	2.1% 7/326 • Number of events 9 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.	10.8% 35/324 • Number of events 42 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.
Gastrointestinal disorders Nausea	3.1% 10/326 • Number of events 13 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.	19.4% 63/324 • Number of events 73 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.
Gastrointestinal disorders Vomiting	1.8% 6/326 • Number of events 10 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.	6.5% 21/324 • Number of events 25 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.
Metabolism and nutrition disorders Decreased appetite	1.2% 4/326 • Number of events 4 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.	6.5% 21/324 • Number of events 21 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.
Metabolism and nutrition disorders Hypoglycaemia	12.6% 41/326 • Number of events 89 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.	4.6% 15/324 • Number of events 31 Safety analyses were performed on the all participants as treated population (defined as participants who received at least 1 dose of study therapy). Participants were included in the reporting group corresponding to the actual study treatment received. Three participants randomized to therapy did not receive any study therapy.

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

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