Efficacy and Safety of Switching From Sitagliptin to Liraglutide in Subjects With Type 2 Diabetes Not Achieving Adequate Glycaemic Control on Sitagliptin and Metformin

Phase 4

Completed

Conditions: Diabetes
Diabetes Mellitus, Type 2

Interventions: Drug: liraglutide
Drug: sitagliptin
Drug: placebo

Registration Number: NCT01907854

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Asia, Europe and North America. The aim of the trial is to investigate the efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes not achieving adequate glycaemic control on sitagliptin and metformin.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 407

Inclusion Criteria

- Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
- Subjects diagnosed with type 2 diabetes and treated with metformin equal to or above 1500 mg/day (or maximum tolerated dose equal to or above 1000 mg/day) and sitagliptin 100 mg/day, both at a stable dose for at least 90 days prior to screening. Stable is defined as unchanged medication and dose
- HbA1c 7.5% - 9.5% (58 mmol/mol - 80 mmol/mol) (both inclusive)
- Body mass index equal to or above 20 kg/m^2

Exclusion Criteria

- Any chronic disorder or severe disease which at the discretion of the investigator might jeopardise subject's safety or compliance with the protocol
- Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. An exception is short-term treatment (equal to or less than 7 days in total) with insulin in connection with intercurrent illness
- Female who is pregnant, breast-feeding, intends to become pregnant or of child-bearing potential not using adequate contraceptive methods (adequate contraceptive measures as required by local regulations or practice)
- History of chronic pancreatitis or idiopathic acute pancreatitis
- Screening calcitonin value equal to or above 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)
- Impaired liver function, defined as alanine aminotransferase equal to or above 2.5 times upper normal limit
- Impaired renal function defined as estimated glomerular filtration rate 60 mL/min/1.73 m^2 per modification of diet in renal disease formula
- Any episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack or other significant cardiovascular event as judged by the investigator within 90 days prior to screening
- Heart failure, New York Heart Association class IV
- Uncontrolled treated or untreated hypertension (systolic blood pressure equal to or above 180 mmHg and/or diastolic blood pressure equal to or above 100 mmHg)

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sitagliptin + metformin + liraglutide placebo	placebo	-
Liraglutide + metformin + sitagliptin placebo	placebo	-
Liraglutide + metformin + sitagliptin placebo	liraglutide	-
Sitagliptin + metformin + liraglutide placebo	sitagliptin	-

Primary Outcome Measures

Name	Time	Method
Change in HbA1c (Glycosylated Haemoglobin)	From baseline to week 26	Change from baseline in HbA1c was analysed after 26 weeks of treatment. Analysis population set: full analysis set (FAS); all randomised subjects receiving at least one dose of any of the trial products. Missing values were imputed using mixed model for repeated measurements (MMRM).

Secondary Outcome Measures

Name	Time	Method
Change in Body Weight	From baseline to week 26	Change from baseline in body weight was analysed after 26 weeks of treatment. Analysis population set: FAS: all randomised subjects receiving at least one dose of any of the trial products. Missing values were imputed using MMRM.
Change in Fasting Plasma Glucose	From baseline to week 26	Change from baseline in fasting plasma glucose was analysed after 26 weeks of treatment. Missing values were imputed using MMRM.
Change in Fasting Blood Lipids	From baseline to week 26	Ratio to baseline in fasting blood lipids (total cholesterol, low density lipoprotein \[LDL\], very low density lipoprotein \[VLDL\], high density lipoprotein \[HDL\], triglycerides, and free fatty acids) were analysed after 26 weeks treatment. Missing values were imputed using MMRM. Here we are presenting ratio to baseline data.
Change in Systolic Blood Pressure and Diastolic Blood Pressure	From baseline to week 26	Change from baseline in systolic and diastolic blood pressure were analysed after 26 weeks of treatment. Missing values were imputed using MMRM.
Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association Target) (y/n)	After 26 weeks of treatment	Number of subjects who achieve HbA1c \<7.0% were analysed after 26 weeks of treatment. Missing values were imputed using MMRM.
Number of Treatment Emergent Adverse Events (TEAEs)	During 26 weeks of treatment plus one week follow-up period.	A treatment emergent adverse event (TEAE) was defined as an event that had an onset date (or increase in severity) on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment. The number of TEAEs was recorded during 26 weeks of treatment plus one week follow-up period.