Efficacy and Safety of FIAsp Compared to Insulin Aspart in Combination With Insulin Glargine and Metformin in Adults With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Asia, Europe and North America. The aim of the trial is to compare FIAsp (faster-acting insulin aspart) to insulin aspart, both in combination with insulin glargine and metformin in adults with type 2 diabetes.

Official Title
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Efficacy and Safety of FIAsp Compared to Insulin Aspart in Combination With Insulin Glargine and Metformin in Adults With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Faster-acting insulin aspart
* Drug: Insulin aspart
* Drug: Insulin glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Type 2 diabetes (diagnosed clinically) for 6 months or longer at time of screening (visit 1) - Treated with basal insulin for at least 6 months prior to screening (visit 1) - Current once daily treatment with insulin NPH (Neutral Protamine Hagedorn), insulin detemir or glargine for at least 3 months prior to the screening visit (visit 1) - Current treatment with: a. metformin with unchanged dosing for at least 3 months prior to screening (visit 1). The metformin dose must be at least 1000 mg or b. metformin in combination with sulfonylurea (SU) or glinide or DPP-IV (dipeptidyl peptidase-4) inhibitors and/or alpha-glucosidase inhibitors (AGI) with unchanged dosing for at least 3 months prior to screening (visit 1). The metformin dose must be at least 1000 mg - HbA1c by central laboratory: a. 7.0 - 9.5% (53 - 80 mmol/mol) (both inclusive) in the metformin group at the screening visit (visit 1) or b. 7.0 - 9.0% (53 - 75 mmol/mol) (both inclusive) in the metformin + other OAD (oral antidiabetic drug) (SU, glinide, DDP-IV inhibitors, AGI) combination group at the screening visit (visit 1) - Body mass index (BMI) equal to or below 40.0 kg/m^2 Exclusion Criteria: - Any use of bolus insulin, except short-term use due to intermittent illness (no longer than 14 days consecutive treatment) and not 3 months prior to the screening visit (visit 1) - Use of GLP-1 (glucagon-like peptide-1) agonists and/or TZDs within the last 3 months prior to screening (visit 1) - Recurrent severe hypoglycaemia (more than 1 severe hypoglycaemic event during the last 12 months) or hypoglycaemic unawareness as judged by the Investigator or hospitalisation for diabetic ketoacidosis during the previous 6 months prior to screening (visit 1) - Cardiovascular disease, within the last 6 months prior to screening (visit 1), defined as: stroke, decompensated heart failure New York Heart Association (NYHA) class III or IV, myocardial infarction, unstable angina pectoris or coronary arterial bypass graft or angioplasty

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: Faster-acting insulin aspart (FIAsp)<br>Meal time faster-acting insulin aspart is given in combination with once daily insulin glargine and metformin in a basal-bolus regimen. Insulin glargine and metformin treatment are open labelled background medication. | Drug: Faster-acting insulin aspart<br>* Mealtime FIAsp administered subcutaneously (s.c., under the skin). Dose individually adjusted.<br>Drug: Insulin glargine<br>* Administered s.c. once daily at subjects' pre-trial dose. Subjects will continue their metformin treatment without changing the frequency or dose throughout the trial.<br>|
| Active Comparator: Insulin aspart<br>Meal time insulin aspart is given in combination with once daily insulin glargine and metformin in a basal-bolus regimen. Insulin glargine and metformin treatment are open labelled background medication. | Drug: Insulin aspart<br>* Mealtime insulin aspart administered subcutaneously (s.c., under the skin). Dose individually adjusted.<br>Drug: Insulin glargine<br>* Administered s.c. once daily at subjects' pre-trial dose. Subjects will continue their metformin treatment without changing the frequency or dose throughout the trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HbA1c | The primary endpoint was change from baseline in HbA1c after 26 weeks of randomized treatment. For this endpoint baseline (week 0) and week 26 have been presented, where week 26 data is end of trial containing last available measurement. | Week 0, Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in 2-hour PPG Increment (Meal Test) | For this endpoint baseline (week 0) and week 26 have been presented, where week 26 data is end of trial containing last available measurement. | Week 0, week 26 | 
| Number of Treatment Emergent Confirmed Hypoglycaemic Episodes | A hypoglycaemic episode was defined as treatment-emergent if the onset of the episode was on or after the first day of exposure to randomized treatment and no later than 1 day after the last day of randomized treatment. A severe or blood glucose (BG) confirmed hypoglycaemic episode was an episode that was severe according to the American Diabetes Association (ADA) classification (an episode that 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 (56 mg/dL) with or without symptoms consistent with hypoglycaemia. | From Week 0 to Week 26. | 
| Change From Baseline in Body Weight | For this endpoint baseline (week 0) and week 26 have been presented, where week 26 data is end of trial containing last available measurement. | Week 0, week 26 |