A Research Study to Compare the Effect of Insulin Degludec and Insulin Glargine on Blood Sugar Levels in People With Type 2 Diabetes - the SWITCH PRO Study

Study Overview
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Brief Summary
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This study compares the effect on blood sugar levels of two medicines: insulin degludec and insulin glargine in people with type 2 diabetes. Participants will be treated with insulin degludec and insulin glargine during two different periods. Which treatment participants get first is decided by chance. Both medicines are approved for use in humans and available on the market. They can already be prescribed by participants' doctors. Participants will get pre-filled insulin pens to inject these insulins with. The study will last for about 41 weeks. Participants will visit the clinic 13 times and have 27 phone calls with the study doctor or study staff. At 12 of the clinic visits they will take blood samples. In order to evaluate the changes in participants' blood sugar level over time, participants will be asked to wear a small (35 millimetres (mm) x 5 mm) sensor on the back of participants' upper arm 3 times during the study. Each time participants must wear the sensor for 2 weeks. This sensor is called FreeStyle Libre Pro®. It has a very small tip which is 0.4 mm thick and is inserted 5 mm under participants' skin. Please note that participants will not be able to see the sensor readings while wearing it. The study doctor will show participants the readings when participants return to the clinic. Participants will be asked to fill in a diary in between visits. Participants will have contact with the study doctor or study staff each week. This is to adjust the dose of participants' study medicines and to ensure that participants are well. Women cannot take part if pregnant, breast-feeding or plan to become pregnant during the study period.

Official Title
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A Randomised, Cross-over, Open-label, Multi-centre Trial Comparing the Effect of Insulin Degludec and Insulin Glargine 100U/mL, With or Without OADs in Subjects With Type 2 Diabetes Using Flash Glucose Monitoring

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Insulin degludec
* Drug: Insulin glargine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age greater than or equal to 18 years at the time of signing informed consent Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening Subjects fulfilling at least one of the below criteria: Experienced at least one severe hypoglycaemic episode within the last year prior to screening (according to the American Diabetes Association definition, January 2018)* Moderate renal impairment defined as estimated glomerular filtration rate value of 30-59 mL/min/1.73 m^2 as defined by Kidney Disease Improving Global Outcomes 2012 at screening Known hypoglycaemic unawareness as indicated by the investigator according to Clarke's questionnaire question 8 at screening Treated with insulin for more than 5 years Episode of hypoglycaemia (defined a glucose alert value of 70 mg/dL (3.9 mmol/L) or less, i.e., Level 1) within the last 12 weeks prior to screening visit Treated with any basal insulin greater than or equal to 90 days prior to the day of screening with or without any of the following anti-diabetic drugs: Metformin Dipeptidyl peptidase-4 inhibitor Sodium-glucose co-transporter 2 inhibitor Alpha-glucosidase-inhibitors (acarbose) Thiazolidinediones Marketed oral combination products only including the products listed above HbA1c less than or equal to 9.5% (80 mmol/mol) at screening confirmed by central laboratory analysis Body mass index less than or equal to 45 kg/m^2 *Hypoglycaemia associated with severe cognitive impairment requiring external assistance for recovery Exclusion Criteria: Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, intermittent bolus insulin treatment for periods of no longer than 14 days are permitted prior to the day of screening Anticipated initiation or change in concomitant medications known to affect weight or glucose metabolism (e.g., treatment with orlistat, thyroid hormones, or corticosteroids) Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and run-in

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: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin degludec<br>Participants will receive insulin degludec in period 1 and 2 in a cross-over manner. | Drug: Insulin degludec<br>* Participants will receive insulin degludec U100 subcutaneous (s.c.) injection once daily for 36 weeks. Doses will be adjusted according to the fasting self-measured plasma glucose (SMPG) values. Participants earlier treated with one or more allowed oral antidiabetic drug(s) (OAD(s)), should continue their pre-trial OAD(s) treatment throughout the trial.<br>* Other names: Tresiba®;|
| Active Comparator: Insulin glargine<br>Participants will receive insulin glargine in period 1 and 2 in a cross-over manner. | Drug: Insulin glargine<br>* Participants will receive insulin glargine U100 s.c. injection once daily for 36 weeks. Doses will be adjusted according to the fasting SMPG values. Participants earlier treated with one or more allowed OAD(s), should continue their pre-trial OAD(s) treatment throughout the trial.<br>* Other names: Lantus®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Time Spent in Glycaemic Target Range 70-180 mg/dL (3.9-10.0 mmol/L) Both Inclusive, Using Flash Glucose Monitoring (FGM) | The percentage of time spent in glycaemic target range was calculated as the number of recorded measurements in glycaemic target range (70-180 milligrams per deciliter [mg/dL] (3.9-10.0 millimoles per litre [mmol/L]), both inclusive) divided by the total number of recorded measurements. The endpoint is based on data recorded by FGM system. It was required that at least 70% of the planned FGM measurements during weeks 16-17 and weeks 34-35 were available for endpoint data to be included in the analysis. | During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time Spent in Tight Glycaemic Target Range 70-140 mg/dL (3.9-7.8 mmol/L) Both Inclusive, Using Flash Glucose Monitoring | The percentage of time spent in tight glycaemic target range 70-140 mg/dL (3.9-7.8 mmol/L) both inclusive, during the 2-week maintenance periods using FGM (visit 9-21 (week 16-17) and visit 37-39 (week 34-35)). | During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2). | 
| Time Spent in Nocturnal Glycaemic Target Range 70-140 mg/dL (3.9-7.8 mmol/L) Both Inclusive, in the Nocturnal Period (00:01 am - 05:59 am Both Inclusive) Using Flash Glucose Monitoring | Percentage of time spent in nocturnal glycaemic target range 70-140 mg/dL (3.9-7.8 mmol/L) both inclusive, in the nocturnal period (00:01 am - 05:59 am both inclusive) during the 2-week maintenance periods using FGM (visit 19-21 (week 16-17) and visit 37-39 (week 34-35)). | During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2). | 
| Level of Glycated Haemoglobin (HbA1c) - Percentage | Level of HbA1c after two weeks of maintenance periods (Visit 19-21 (week 16-17) and Visit 37-39 (week 34-35)). | After the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2). | 
| Level of Glycated Haemoglobin (HbA1c) - mmol/Mol | Level of HbA1c after two weeks of maintenance periods (Visit 19-21 (week 16-17) and Visit 37-39 (week 34-35)). | After the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2). | 
| Mean Glucose Levels Using Flash Glucose Monitoring (FGM) | Mean glucose levels (mmol/L) during the 2-week maintenance periods using FGM (visit 19-21 (week 16-17) and visit 37-39 (week 34-35)). | During the 2-week maintenance period: weeks 16-17 (period-1) and weeks 34-35 (period-2). |