Diabetes, Diabetes Mellitus, Type 2
Conditions
Brief summary
This trial is conducted in Asia. The aim of this trial is to investigate the efficacy and safety of liraglutide compared to sitagliptin, both as add-on to metformin in Chinese subjects with type 2 diabetes inadequately controlled on metformin monotherapy. Eligible subjects will continue their metformin background treatment during the trial.
Interventions
DRUGliraglutide
Administered subcutaneously (s.c., under the skin) once daily as add-on to the subject's stable pre-trial metformin dose.
DRUGsitagliptin
Administered orally once daily as add-on to the subject's stable pre-trial metformin dose.
Sponsors
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Male or female, age at least 18 years and below 80 years at the time of signing informed consent * Subjects diagnosed type 2 diabetes mellitus and treated with metformin monotherapy at a stable dose of at least 1500 mg daily or maximum tolerated dose above or equal to 1000 mg daily for at least 60 days prior to screening * HbA1c 7.0-10.0% (both inclusive) * Body mass index below or equal to 45.0 kg/m\^2
Exclusion criteria
* Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 60 days prior to screening. An exception is short-term treatment (below or equal to 7 days in total) with insulin in connection with intercurrent illness * History of chronic pancreatitis or idiopathic acute pancreatitis * Any chronic disorder or severe disease which at the discretion of the investigator might jeopardise subject's safety or compliance with the protocol * Screening calcitonin value above or equal to 50 ng/l * Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2 * Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer) * Any contraindications to liraglutide, sitagliptin or metformin according to local labelling
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Glycosylated Haemoglobin (HbA1c) | Week 0, week 26 | Mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Fasting Plasma Glucose | Week 0, week 26 | Mean change from baseline in fasting plasma glucose (FPG) at Week 26. |
| Change From Baseline in 7-point Self-measured Plasma Glucose Profile | Week 0, week 26 | 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. |
| Subjects Who Achieve (Yes/no) HbA1c Below 7.0 % (American Diabetes Association Target) | After 26 weeks of treatment | Calculated as the percentage of subjects achieving treatment target of HbA1c \< 7.0% at Week 26 |
| Subjects Who Achieve (Yes/no) HbA1c Below or Equal to 6.5 % (American Association of Clinical Endocrinologists Target) | After 26 weeks of treatment | Calculated as the percentage of subjects achieving treatment target of HbA1c \<= 6.5% at Week 26 |
| Number of Confirmed Hypoglycaemic Episodes | Weeks 0-26 | confirmed hypoglycaemic episode defined as severe (unable to treat her/himself) or biochemically confirmed by a plasma glucose \< 3.1 mmol/L |
Countries
China
Participant flow
Recruitment details
This trial was conducted at 25 sites in China.
Pre-assignment details
Between screening and randomisation, eligible subjects were to continue their usual pre-trial metformin dose and dosing frequency.
Participants by arm
| Arm | Count |
|---|---|
| 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. | 183 |
| 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). | 184 |
| Total | 367 |
Baseline characteristics
| Characteristic | Sitagliptin | Total | Liraglutide |
|---|---|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 11 | 51.5 years STANDARD_DEVIATION 10.9 | 51.7 years STANDARD_DEVIATION 10.7 |
| Body mass index (BMI) | 27.16 kg/m^2 STANDARD_DEVIATION 4.029 | 27.24 kg/m^2 STANDARD_DEVIATION 3.72 | 27.32 kg/m^2 STANDARD_DEVIATION 3.389 |
| Body weight | 75.78 kg STANDARD_DEVIATION 15.089 | 75.98 kg STANDARD_DEVIATION 14.33 | 76.17 kg STANDARD_DEVIATION 13.562 |
| Duration of diabetes | 5.22 years STANDARD_DEVIATION 5.4 | 5.27 years STANDARD_DEVIATION 4.92 | 5.31 years STANDARD_DEVIATION 4.39 |
| Fasting plasma glucose (FPG) | 9.46 mmol/L STANDARD_DEVIATION 2.237 | 9.36 mmol/L STANDARD_DEVIATION 2.226 | 9.26 mmol/L STANDARD_DEVIATION 2.216 |
| Glycosylated haemoglobin A1c (HbA1c) | 8.11 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.78 | 8.12 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.806 | 8.14 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.833 |
| Sex: Female, Male Female | 67 Participants | 148 Participants | 81 Participants |
| Sex: Female, Male Male | 117 Participants | 219 Participants | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 65 / 183 | 14 / 184 |
| serious Total, serious adverse events | 3 / 183 | 6 / 184 |
Outcome results
Primary
Change From Baseline in Glycosylated Haemoglobin (HbA1c)
Mean change from baseline in glycosylated haemoglobin A1c (HbA1c) at Week 26.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change From Baseline in Glycosylated Haemoglobin (HbA1c) | -1.666 Percent (%) glycosylated haemoglobin | Standard Deviation 0.9982 |
| Sitagliptin | Change From Baseline in Glycosylated Haemoglobin (HbA1c) | -0.969 Percent (%) glycosylated haemoglobin | Standard Deviation 0.9742 |
Secondary
Change From Baseline in 7-point Self-measured Plasma Glucose Profile
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change From Baseline in 7-point Self-measured Plasma Glucose Profile | -2.25 mmol/L | Standard Deviation 2.244 |
| Sitagliptin | Change From Baseline in 7-point Self-measured Plasma Glucose Profile | -1.36 mmol/L | Standard Deviation 2.204 |
Secondary
Change From Baseline in Fasting Plasma Glucose
Mean change from baseline in fasting plasma glucose (FPG) at Week 26.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Liraglutide | Change From Baseline in Fasting Plasma Glucose | -2.347 mmol/L | Standard Deviation 2.1655 |
| Sitagliptin | Change From Baseline in Fasting Plasma Glucose | -1.205 mmol/L | Standard Deviation 2.2961 |
Secondary
Number of Confirmed Hypoglycaemic Episodes
confirmed hypoglycaemic episode defined as severe (unable to treat her/himself) or biochemically confirmed by a plasma glucose \< 3.1 mmol/L
Time frame: Weeks 0-26
Population: Safety analysis set included all subjects receiving at least one dose of investigational product.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide | Number of Confirmed Hypoglycaemic Episodes | 2 episodes |
| Sitagliptin | Number of Confirmed Hypoglycaemic Episodes | 1 episodes |
Secondary
Subjects Who Achieve (Yes/no) HbA1c Below 7.0 % (American Diabetes Association Target)
Calculated as the percentage of subjects achieving treatment target of HbA1c \< 7.0% at Week 26
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide | Subjects Who Achieve (Yes/no) HbA1c Below 7.0 % (American Diabetes Association Target) | 76.5 percentage of subjects |
| Sitagliptin | Subjects Who Achieve (Yes/no) HbA1c Below 7.0 % (American Diabetes Association Target) | 52.6 percentage of subjects |
Secondary
Subjects Who Achieve (Yes/no) HbA1c Below or Equal to 6.5 % (American Association of Clinical Endocrinologists Target)
Calculated as the percentage of subjects achieving treatment target of HbA1c \<= 6.5% at Week 26
Time frame: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Liraglutide | Subjects Who Achieve (Yes/no) HbA1c Below or Equal to 6.5 % (American Association of Clinical Endocrinologists Target) | 61.7 percentage of subjects |
| Sitagliptin | Subjects Who Achieve (Yes/no) HbA1c Below or Equal to 6.5 % (American Association of Clinical Endocrinologists Target) | 26.3 percentage of subjects |