Efficacy and Safety of Liraglutide Versus Placebo as add-on to Existing Diabetes Medication in Subjects With Type 2 Diabetes and Moderate Renal Impairment

Phase 3

Completed

Conditions: Diabetes
Diabetes Mellitus, Type 2

Interventions: Drug: placebo
Drug: liraglutide

Registration Number: NCT01620489

Lead Sponsor: Novo Nordisk A/S

Brief Summary: This trial is conducted in Europe and the United States of America (USA). The aim of this trial is to investigate the efficacy and safety of liraglutide in subjects with type 2 diabetes and moderate renal impairment.

The trial medication will be add-on to the subject's stable pre-trial OAD and/or insulin regimen.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 279

Inclusion Criteria

Subjects diagnosed with type 2 diabetes with stable diabetes treatment (unchanged medication and unchanged dose) for 90 days prior to the screening visit including: Monotherapy or any duo-combinations of metformin and/or SUs and/or pioglitazone. Metformin should be used with caution in subjects with moderate renal failure and must be used in accordance with local metformin labelling or guidelines. Or Monotherapy or any combinations of metformin and/or pioglitazone and/or basal or premix insulin. Insulin adjustments (total daily dose) below or equal to 10% within 90 days prior to the screening visit as confirmed by the investigator are acceptable. Metformin should be used with caution in subjects with moderate renal failure and must be used in accordance with local metformin labelling or guidelines. Combination of pioglitazone and insulin should be used with caution and according to local labelling or guidelines
HbA1c 7-10% (both inclusive)
Moderate renal impairment diagnosed more than 90 days prior to the screening visit and confirmed by an eGFR (glomerular filtration rate) of 30-59 mL/min/1.73 m2 per MDRD (modification of diet in renal disease) formula at the screening visit
Body Mass Index (BMI) 20-45 kg/m^2 (both inclusive)

Exclusion Criteria

Recurrent severe hypoglycaemia or hypoglycaemic unawareness as judged by the investigator
Treatment with antidiabetic medication(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. Previous short-term (below or equal to 7 days in total) treatment with rapid-or short-acting insulin in connection with intercurrent illness is allowed at the discretion of the investigator
Impaired liver function, defined as ALAT (alanine aminotransferase) above or equal to 2.5 times upper normal limit
History of chronic pancreatitis or idiopathic acute pancreatitis
Within the past 180 days any of the following: Episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack (TIA) or other significant cardiovascular event (including e.g. arrhythmias or conduction delays on ECG (electrocardiogram))
Heart failure defined as New York Heart Association (NYHA) class IV
A systolic blood pressure above or equal to 180 mmHg or a diastolic blood pressure above or equal to 100 mmHg
Rapidly progressing renal disease (e.g., acute glomerulonephritis) at the discretion of the investigator
Use of immunosuppressive treatment within 90 days prior to screening
Diagnosis or treatment for cancer in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)
Proliferative retinopathy or maculopathy requiring acute treatment as judged by the investigator

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	placebo	-
Lira 1.8 mg	liraglutide	-

Primary Outcome Measures

Name	Time	Method
Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in HbA1c (%) (Glycosylated Haemoglobin)	Week 0, Week 26	Calculated as the estimated mean change from baseline in HbA1c (%) after 26 Weeks of treatment based on the statistical model.

Secondary Outcome Measures

Name	Time	Method
Estimated Proportion of Responders Achieving HbA1c <7.0% and no Weight Gain After 26 Weeks of Treatment	At week 26	Calculated as estimated percentage of subjects achieving HbA1c \<7.0% and no weight gain after 26 weeks of treatment based on the statistical model.
Estimated Proportion of Responders Achieving HbA1c <7.0% and no Minor or Severe Hypoglycaemic Episodes After 26 Weeks of Treatment	At week 26	Calculated as estimated percentage of subjects achieving HbA1c \<7.0% and no minor or severe hypoglycaemic episodes observed within 26 weeks of treatment based on the statistical model.
Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in Body Mass Index (BMI)	Week 0, week 26	Calculated as estimated mean change in BMI (kg/m˄2) from baseline to Week 26 based on the statistical model.
Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in Self-measured Plasma Glucose (SMPG) 7-point Profiles	Week 0, week 26	SMPG was measured before and 90 minutes after breakfast, lunch and dinner and at bedtime at Week 0, 12 and 26. A summary measure of the 7 values was derived for each applicable visit as the area under the curve divided by the period of time elapsed between the first and last measurement. The change from baseline to week 26 was estimated using the statistical model.
Estimated Mean Ratio to Baseline and Observed Coefficient of Variation in Renal Function-estimated Glomerular Filtration Rate (eGFR) (to Check How Well the Kidneys Are Functioning Using Modification of Diet in Renal Disease (MDRD) Formula)	Week 0, week 26	Calculated as the estimated ratio to baseline in eGFR (mL/min/1.73m˄2) after 26 Weeks of treatment based on the statistical model.