The Efficacy of Insulin Degludec/Liraglutide as add-on Therapy in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on Sulphonylurea With or Without Metformin Therapy

Study Overview
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Brief Summary
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This trial is conducted in Asia, Europe and the United States of America (USA). The aim of this trial is to investigate the efficacy and safety of insulin degludec/liraglutide in insulin naïve subjects inadequately controlled with SU (sulphonylurea) alone or in combination with metformin. All subjects will continue their pre-trial SU treatment with or without metformin treatment without changing the frequency or dose throughout the trial.

Official Title
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The Efficacy of Insulin Degludec/Liraglutide as add-on Therapy in Controlling Glycaemia in Adults With Type 2 Diabetes Inadequately Controlled on Sulphonylurea With or Without Metformin Therapy

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: insulin degludec/liraglutide
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with type 2 diabetes mellitus HbA1c 7.0-9.0% (53-75 mmol/mol) (both inclusive) Subjects on stable daily dose of sulphonylurea (above or equal to half of the max approved dose according to local label) with or without metformin (above or equal to 1500 mg or max tolerated dose) for at least 90 days prior to screening visit (Visit 1) Body Mass Index (BMI) below or equal to 40 kg/m^2 Exclusion Criteria: Any use of oral anti-diabetic drugs (OADs) (other than SU in monotherapy or in combinationwith metformin) below or equal to 90 days prior to screening visit (Visit 1) Use of any drug (other than SU in monotherapy or in combination with metformin), which in the Investigators opinion could interfere with the blood glucose level (e.g. systemic corticosteroids) Previous treatment with glucagon-like peptide-1 (GLP-1) receptor agonist (e.g. exenatide, liraglutide) Treatment with any insulin regimen (short term treatment due to intercurrent illness including gestational diabetes is allowed at the discretion of the Investigator) Screening calcitonin above or equal to 50 ng/l Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN2) Cardiovascular disorders defined as: congestive heart failure (New York Heart Association (NYHA) class III-IV), diagnosis of unstable angina pectoris, cerebral stroke and/or myocardial infarction within the past 52 weeks prior to screening visit (Visit 1) and/or planned coronary,carotid or peripheral artery revascularisation procedures Proliferative retinopathy requiring acute treatment or maculopathy (macular oedema) according to the Investigator's opinion Subjects with a clinical significant, active (during the past 12 months) disease of the gastrointestinal, pulmonary, endocrinological (except for the Type 2 Diabetes Mellitus),neurological, genitourinary or haematological system that in the opinion of the Investigator,may confound the results of the trial or pose additional risk in administering trial product History of chronic pancreatitis or idiopathic acute pancreatitis

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin degludec/liraglutide<br> | Drug: insulin degludec/liraglutide<br>* Injected subcutaneously (under the skin) once daily. Dose individually adjusted.<br>|
| Placebo Comparator: Placebo<br> | Drug: placebo<br>* Injected subcutaneously (under the skin) once daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Glycosylated Haemoglobin (HbA1c) | Change in HbA1c from baseline to 26 weeks. | Week 0, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Responders Achieving Pre-defined Target: HbA1c Below 7.0% (53 mmol/Mol) | Percentage of subjects having HbA1c below 7% at week 26. | Week 26 | 
| Responders Achieving Pre-defined Target: HbA1c Below or Equal to 6.5% (48 mmol/Mol) | Percentage of subjects having HbA1c below 6.5% at week 26 | Week 26 | 
| Change From Baseline in Fasting Plasma Glucose (FPG) | Change from baseline in FPG at week 26. | Week 0, week 26 | 
| Change From Baseline in Body Weight | Change from baseline in body weight at week 26. | Week 0, week 26 | 
| Number of Treatment Emergent (Confirmed) Hypoglycaemic Episodes | An event was treatment emergent if the onset of the episode occurs after the first administration of trial product and no later than 7 days after last trial product administration. Confirmed hypoglycaemic episodes were defined as hypoglycaemic episodes that were either severe or minor. Minor hypoglycaemic episodes were defined as: An episode with symptoms consistent with hypoglycaemia and confirmed by blood glucose value <2.8 mmol/L (50 mg/dL) or plasma glucose <3.1 mmol/L (56 mg/dL) and which was handled by the subject himself/herself. Any asymptomatic PG value <3.1 mmol/L (56 mg/dL) or blood glucose value <2.8 mmol/L (50 mg/dL). Severe hypoglycemia was defined as an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Reported values are hypoglycemia event rate per 100 patient-years of exposure (PYE). | After 26 weeks of treatment | 
| Number of Adverse Events (AEs) | An AE was any unfavourable and unintended sign (including an abnormal laboratory finding), symptom or disease temporally associated with the use of a product, whether or not considered related to the product. Reported values are hypoglycemia event rate per 100 PYE. | After 26 weeks of treatment |