Trial Outcomes & Findings for The Efficacy and Safety of Liraglutide Compared to Sitagliptin, Both in Combination With Metformin in Chinese Subjects With Type 2 Diabetes (NCT NCT02008682)

NCT ID: NCT02008682

Last Updated: 2017-03-09

Results Overview

Mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 368 participants
• Primary outcome timeframe: Week 0, week 26
• Results posted on: 2017-03-09

Participant Flow

This trial was conducted at 25 sites in China.

Between screening and randomisation, eligible subjects were to continue their usual pre-trial metformin dose and dosing frequency.

Participant milestones

Measure	Liraglutide subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Overall Study STARTED	184	184
Overall Study Exposed	183	184
Overall Study COMPLETED	157	170
Overall Study NOT COMPLETED	27	14

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

The Efficacy and Safety of Liraglutide Compared to Sitagliptin, Both in Combination With Metformin in Chinese Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Measure	Liraglutide n=183 Participants subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=184 Participants orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).	Total n=367 Participants Total of all reporting groups
Age, Continuous	51.7 years STANDARD_DEVIATION 10.7 • n=93 Participants	51.4 years STANDARD_DEVIATION 11.0 • n=4 Participants	51.5 years STANDARD_DEVIATION 10.9 • n=27 Participants
Sex: Female, Male Female	81 Participants n=93 Participants	67 Participants n=4 Participants	148 Participants n=27 Participants
Sex: Female, Male Male	102 Participants n=93 Participants	117 Participants n=4 Participants	219 Participants n=27 Participants
Body mass index (BMI)	27.32 kg/m^2 STANDARD_DEVIATION 3.389 • n=93 Participants	27.16 kg/m^2 STANDARD_DEVIATION 4.029 • n=4 Participants	27.24 kg/m^2 STANDARD_DEVIATION 3.720 • n=27 Participants
Body weight	76.17 kg STANDARD_DEVIATION 13.562 • n=93 Participants	75.78 kg STANDARD_DEVIATION 15.089 • n=4 Participants	75.98 kg STANDARD_DEVIATION 14.330 • n=27 Participants
Duration of diabetes	5.31 years STANDARD_DEVIATION 4.39 • n=93 Participants	5.22 years STANDARD_DEVIATION 5.40 • n=4 Participants	5.27 years STANDARD_DEVIATION 4.92 • n=27 Participants
Fasting plasma glucose (FPG)	9.26 mmol/L STANDARD_DEVIATION 2.216 • n=93 Participants	9.46 mmol/L STANDARD_DEVIATION 2.237 • n=4 Participants	9.36 mmol/L STANDARD_DEVIATION 2.226 • n=27 Participants
Glycosylated haemoglobin A1c (HbA1c)	8.14 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.833 • n=93 Participants	8.11 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.780 • n=4 Participants	8.12 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.806 • n=27 Participants

PRIMARY outcome

Timeframe: Week 0, week 26

Population: Full analysis set was defined as all randomised and exposed subjects who had any post randomisation data. Missing data was imputed using a mixed model for repeated measurements. The subjects would not contribute to the analyses if they didn't have a corresponding post-baseline value.

Mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26.

Outcome measures

Measure	Liraglutide n=162 Participants subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=175 Participants orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Change From Baseline in Glycosylated Haemoglobin (HbA1c)	-1.666 Percent (%) glycosylated haemoglobin Standard Deviation 0.9982	-0.969 Percent (%) glycosylated haemoglobin Standard Deviation 0.9742

SECONDARY outcome

Timeframe: Week 0, week 26

Population: Full analysis set was defined as all randomised and exposed subjects who had any post randomisation data. Missing data was imputed using a mixed model for repeated measurements. The subjects would not contribute to the analyses if they didn't have a corresponding post-baseline value.

Mean change from baseline in fasting plasma glucose (FPG) at Week 26.

Outcome measures

Measure	Liraglutide n=168 Participants subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=180 Participants orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Change From Baseline in Fasting Plasma Glucose	-2.347 mmol/L Standard Deviation 2.1655	-1.205 mmol/L Standard Deviation 2.2961

SECONDARY outcome

Timeframe: Week 0, week 26

Population: Full analysis set was defined as all randomised and exposed subjects who had any post randomisation data. Missing data was imputed using a mixed model for repeated measurements. The subjects would not contribute to the analyses if they didn't have a corresponding post-baseline value.

Mean change from baseline in mean of 7-point self-measured plasma glucose at week 26. The 7-point self-measured plasma glucose levels were measured before and after (120 minutes after the start of the meal) the three main meals (breakfast, lunch and dinner), and at bed time.

Outcome measures

Measure	Liraglutide n=161 Participants subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=174 Participants orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Change From Baseline in 7-point Self-measured Plasma Glucose Profile	-2.25 mmol/L Standard Deviation 2.244	-1.36 mmol/L Standard Deviation 2.204

SECONDARY outcome

Timeframe: After 26 weeks of treatment

Population: Full analysis set was defined as all randomised and exposed subjects who had any post randomisation data. Missing data was imputed using a mixed model for repeated measurements. The subjects would not contribute to the analyses if they didn't have a corresponding post-baseline value.

Calculated as the percentage of subjects achieving treatment target of HbA1c < 7.0% at Week 26

Outcome measures

Measure	Liraglutide n=162 Participants subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=175 Participants orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Subjects Who Achieve (Yes/no) HbA1c Below 7.0 % (American Diabetes Association Target)	76.5 percentage of subjects	52.6 percentage of subjects

SECONDARY outcome

Timeframe: After 26 weeks of treatment

Population: Full analysis set was defined as all randomised and exposed subjects who had any post randomisation data. Missing data was imputed using a mixed model for repeated measurements. The subjects would not contribute to the analyses if they didn't have a corresponding post-baseline value.

Calculated as the percentage of subjects achieving treatment target of HbA1c <= 6.5% at Week 26

Outcome measures

Measure	Liraglutide n=162 Participants subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=175 Participants orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Subjects Who Achieve (Yes/no) HbA1c Below or Equal to 6.5 % (American Association of Clinical Endocrinologists Target)	61.7 percentage of subjects	26.3 percentage of subjects

SECONDARY outcome

Timeframe: Weeks 0-26

Population: Safety analysis set included all subjects receiving at least one dose of investigational product.

confirmed hypoglycaemic episode defined as severe (unable to treat her/himself) or biochemically confirmed by a plasma glucose < 3.1 mmol/L

Outcome measures

Measure	Liraglutide n=183 Participants subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=184 Participants orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Number of Confirmed Hypoglycaemic Episodes	2 episodes	1 episodes

Adverse Events

Liraglutide

Serious events: 3 serious events

Other events: 65 other events

Deaths: 0 deaths

Sitagliptin

Serious events: 6 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Measure	Liraglutide n=183 participants at risk subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=184 participants at risk orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Gastrointestinal disorders Gastric ulcer	0.00% 0/183 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.54% 1/184 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Gastrointestinal disorders Haemorrhoids	0.00% 0/183 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.54% 1/184 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thyroid cancer	0.00% 0/183 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.54% 1/184 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Thymoma malignant	0.00% 0/183 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.54% 1/184 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Cardiac disorders Atrial fibrillation	0.00% 0/183 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.54% 1/184 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Ear and labyrinth disorders Sudden hearing loss	0.55% 1/183 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.00% 0/184 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Infections and infestations Bronchitis	0.55% 1/183 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.00% 0/184 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.55% 1/183 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.00% 0/184 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Nervous system disorders Cerebral infarction	0.00% 0/183 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.54% 1/184 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.

Other adverse events

Measure	Liraglutide n=183 participants at risk subcutaneously, once-daily dose of liraglutide 1.8 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily). Liraglutide dose was escalated from 0.6 mg/day to 1.8 mg/day during 3-4 weeks.	Sitagliptin n=184 participants at risk orally, once-daily dose of sitagliptin 100 mg with metformin at pre-trial stable dose (at least 1500 mg or maximum tolerated dose at least 1000 mg daily).
Gastrointestinal disorders Nausea	14.8% 27/183 • Number of events 30 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.54% 1/184 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Gastrointestinal disorders Diarrhoea	8.2% 15/183 • Number of events 16 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	2.2% 4/184 • Number of events 4 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Metabolism and nutrition disorders Decreased appetite	10.9% 20/183 • Number of events 20 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	0.54% 1/184 • Number of events 1 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.
Investigations Lipase increased	6.0% 11/183 • Number of events 11 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.	4.3% 8/184 • Number of events 9 • Weeks 0-26 Treatment emergent adverse event defined as an event that had onset date (or increase in severity) on or after the first day of exposure to trial product and no later than seven days after the last day of trial product. Safety analysis set defined as all exposed subjects.

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