Efficacy in Controlling Glycaemia With Victoza® (Liraglutide) as add-on to Metformin vs. OADs as add-on to Metformin After up to 104 Weeks of Treatment in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted globally. The aim of the trial is to investigate efficacy in controlling glycaemia with Victoza® (liraglutide) as add-on to metformin background treatment vs. OADs as add-on to metformin background treatment for 104 weeks of treatment in subjects with type 2 diabetes.

Official Title
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Efficacy in Controlling Glycaemia With Victoza® (Liraglutide) as add-on to Metformin vs. OADs as add-on to Metformin After up to 104 Weeks of Treatment in Subjects With Type 2 Diabetes Inadequately Controlled With Metformin Monotherapy and Treated in a Primary Care Setting

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: liraglutide
* Drug: alpha-glucosidase inhibitors
* Drug: DPP-4 inhibitors
* Drug: meglitinides
* Drug: SGLT-2 inhibitors
* Drug: sulphonylurea
* Drug: thiazolidinediones


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Male or female at least 18 years of age at the time of signing informed consent - Subjects diagnosed (clinically) with type 2 diabetes equal to or above 90 days prior to the screening visit - Stable daily dose of metformin as monotherapy equal to or above 1500 mg or maximum tolerated dose within 60 days prior to the screening visit - HbA1c 7.5-9.0% (59-75 mmol/mol) (both inclusive) and measured within the last 90 days prior to the screening visit Exclusion Criteria: - Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using adequate contraceptive methods (adequate contraceptive measures as required by local regulation or practice) - Treatment with any medication for the indication of diabetes other than metformin in a period of 60 days before the screening visit. An exception is short-term treatment (below or equal to 7 days in total) with insulin in connection with intercurrent illness - Receipt of any investigational medicinal product within 30 days before the screening visit - Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Liraglutide 1.8 mg<br>Add-on to metformin | Drug: liraglutide<br>* Trial product will be prescribed by the investigator and dispensed by pharmacy or similar.<br>|
| Active Comparator: OAD<br>Add-on to metformin. Treatment with one OAD selected at the discretion of the investigator. Subjects randomised to the OAD arm must remain on the same OAD throughout the trial. | Drug: alpha-glucosidase inhibitors<br>* Trial product will be prescribed by the investigator and dispensed by pharmacy or similar.<br>Drug: DPP-4 inhibitors<br>* Trial product will be prescribed by the investigator and dispensed by pharmacy or similar.<br>Drug: meglitinides<br>* Trial product will be prescribed by the investigator and dispensed by pharmacy or similar.<br>Drug: SGLT-2 inhibitors<br>* Trial product will be prescribed by the investigator and dispensed by pharmacy or similar.<br>Drug: sulphonylurea<br>* Trial product will be prescribed by the investigator and dispensed by pharmacy or similar.<br>Drug: thiazolidinediones<br>* Trial product will be prescribed by the investigator and dispensed by pharmacy or similar.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Inadequate Glycaemic Control | Inadequate glycaemic control was defined as glycosylated haemoglobin (HbA1c) of 7.0% (53 mmol/mol) or greater at two consecutive visits after the first 26 weeks of treatment and up to 104 weeks. 25%, median (50%) and 75% percentiles for the cumulative distribution function, are obtained from the Kaplan-Meier survival function. HbA1c was recorded at weeks 38, 52, 65, 78, 91 and 104. | Weeks 26-104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Premature Treatment Discontinuation (for Any Reason Including Inadequate Glycaemic Control) | The time to premature treatment discontinuation (for any reason including inadequate glycaemic control) was analysed and presented using the generalised log rank test. 25%, median (50%) and 75% percentiles for the cumulative distribution function, are obtained from the Kaplan-Meier survival function. | Weeks 0-104 | 
| Change in HbA1c | Change from baseline (week 0) in HbA1c at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Participants Who Achieve HbA1c ≤6.5% (Yes/No) | Participants who achieved HbA1c ≤6.5% (yes/no) is presented. | Week 104/Premature treatment discontinuation | 
| Participants Who Achieve HbA1c ≤7.0% Without Weight Gain | Participants who achieved HbA1c ≤7.0% without weight gain (yes/no) is presented. | Week 104/Premature treatment discontinuation | 
| Participants Who Achieve HbA1c ≤7.0% Without Treatment Emergent Severe Hypoglycaemic Episodes or BG Confirmed Symptomatic Hypoglycaemic Episodes | Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value <3.1 millimoles per liter (mmol/L) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than the day after the last day on trial product. Participants who achieved HbA1c ≤7.0% without treatment emergent severe hypoglycaemic episodes or BG confirmed symptomatic hypoglycaemic episodes (yes/no) is presented. | Week 104/Premature treatment discontinuation | 
| Participants Who Achieve HbA1c ≤7.0% Without Weight Gain and no Treatment Emergent Severe Hypoglycaemic Episodes or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes | Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than the day after the last day on trial product. Participants who achieved HbA1c ≤7.0% without weight gain and no treatment emergent severe hypoglycaemic episodes or BG confirmed symptomatic hypoglycaemic episodes (yes/no) is presented. | Week 104/Premature treatment discontinuation | 
| Change in Fasting Plasma Glucose (FPG) | Change from baseline (week 0) in FPG at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Change in Body Weight | Change from baseline (week 0) in body weight at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Change in Body Mass Index (BMI) | Change from baseline (week 0) in BMI at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Change in Blood Pressure (Systolic and Diastolic Blood Pressure) | Change from baseline (week 0) in systolic and diastolic blood pressure at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Number of Severe Hypoglycaemic Episodes | Severe hypoglycaemic episodes were defined as episodes that required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Number of severe hypoglycaemic episodes that occured during weeks 0-104 are presented. | Weeks 0-104 | 
| Number of Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes | Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Number of severe or BG confirmed symptomatic hypoglycaemic episodes that occured during weeks 0-104 are presented. | Weeks 0-104 | 
| Number of Documented Symptomatic Hypoglycaemic Episodes (ADA) | Documented symptomatic hypoglycaemic were defined as episodes with typical symptoms of hypoglycaemia accompanied by measure plasma glucose concentration <= 3.9 mmol/L. Number of documented symptomatic hypoglycaemic episodes that occured during the weeks 0-104 are presented. | Weeks 0-104 | 
| Number of Serious Adverse Events (SAEs) | A serious adverse event (SAE) was defined as any event that resulted in any of the following: death, life-threatening experience, in-patient hospitalisation or prolongation of existing hospitalisation, persistent or significant disability or incapacity, congenital anomaly or birth defect or suspicion of transmission of infectious agents via the trial product. An SAE was considered as treatment emergent if it had an onset or increase in severity on or after the time of first trial product administration and no later than 7 days after the time of last trial product administration. Number of treatment emergent serious adverse events are presented. | Weeks 0-105 | 
| Number of AEs Leading to Permanent Discontinuation of Trial Product | An adverse event (AE) was any untoward medical occurrence in a participant who administered a product, and which did not necessarily had a causal relationship with this treatment. An AE was considered as treatment emergent if it had an onset or increase in severity on or after the time of first trial product administration and no later than 7 days after the time of last trial product administration. Number of treatment emergent AEs that led to permanent discontinuation of trial product are presented. | Weeks 0-105 | 
| Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides | Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (TC) and triglycerides (TG) at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase | Change from baseline (week 0) in alanine aminotransferase (ALAT), amylase, aspartate aminotransferase (ASAT) and lipase at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Change in Biochemistry- Creatinine, Total Bilirubin | Change from baseline (week 0) in creatinine and total bilirubin (TB) at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Change in Biochemistry- Estimated Glomerular Filtration Rate (eGFR) Serum | The estimated GFR was derived from serum creatinine using the MDRD (Modification of diet in renal disease) formula. eGFR was measured as milliliter per min per specific surface area (mL/min/SSA). | Week 0, week 104/premature treatment discontinuation | 
| Change in Potassium | Change from baseline (week 0) in potassium at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Change in Haemoglobin | Change from baseline (week 0) in haemoglobin at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation | 
| Change in Pulse | Change from baseline (week 0) in pulse at week 104 or at premature treatment discontinuation is presented. | Week 0, week 104/premature treatment discontinuation |