Degludec Glargine U300 Hospital Study

Study Overview
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Brief Summary
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Limited data exist about the use of insulin degludec and insulin glargine U300 in the hospitalized patients. A previous study compared the safety and efficacy of insulin degludec versus insulin glargine U100 for the management of hospitalized patients with type 2 diabetes. However, there is no data comparing the efficacy and safety of insulin degludec versus insulin glargine U300 for the management of hospitalized patients with type 2 diabetes. Accordingly, the proposed study will provide a clinically useful information on the efficacy (blood glucose control) and safety (hypoglycemia) of insulin degludec versus insulin glargine U300 for the management of hospitalized patients with type 2 diabetes.

Detailed Description
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The purpose of this study is to find out if treatment with insulin degludec when compared to insulin glargine U300 will result in similar blood sugar control in hospitalized patients with type 2 diabetes. Primary outcome measure 1. Change in mean daily blood glucose concentration in hospitalized patients [ Time Frame: The first 7 days of therapy ] Blood glucose will be measured before each meal, bedtime and at 3:00 am. Mean daily blood glucose concentration will be calculated to determine differences in inpatient glycemic control in patients with type 2 diabetes treated with basal bolus regimen or basal plus regimen with insulin degludec or glargine U300 once daily plus insulin glulisine before meals. Secondary outcome measures Number of basic glucose readings between 70 mg/dl and 180 mg/dl before meals in hospitalized patients. Blood glucose will be measured before each meal, bedtime and at 3:00 am, and proportion of basic glucose readings between 70 mg/dl and 180 mg/dl will be recorded. Number of hypoglycemic episodes (BG < 70 mg/dl and 54 mg/dl) in hospitalized patients. Blood glucose will be measured before each meal, bedtime and 3:00 am, and number of hypoglycemic episodes (< 70 mg/dl and 54 mg/dl) will be recorded. Number of severe hypoglycemia (< 54 mg/dl) episodes in hospitalized patients Blood glucose will be measured before each meal, bedtime and at 3:00 am, and number of hypoglycemia (< 54 mg/dl) episodes will be recorded. Number of episodes of severe hyperglycemia (BG > 240 mg/dl) in hospitalized patients Blood glucose will be measured before each meal, bedtime and at 3:00 am, and number of severe hyperglycemia (> 240 mg/dl) episodes will be recorded. Daily dose of basal insulin, daily dose of prandial insulin, and total daily dose in hospitalized patients The study team will document day and time of insulin administration of study drug given once daily and prandial- rapid-acting insulin (aspart) given before meals. The study team will also record dose and number of units given as supplement (correction) to correct hyperglycemia. Average blood glucose (mg/dl), percentage time in target, percentage time below target, and percentage time above target in a subgroup of study participants A subgroup of participants (n = 100) will be monitored using continuous glucose monitoring system (CGMS) (FreeStyle Libre). Eligibility criteria Inclusion Criteria: Males or females >30 years admitted to the hospital for elective CABG surgery. A known history of T2D treated either with diet alone, oral monotherapy, any combination of oral antidiabetic agents, short-acting GLP1-RA (exenatide, liraglutide) or insulin therapy except for degludec and glargine U300. Study participants must have a randomization total daily dose (TDD) insulin requirement of at least 20 units per day. Signed, informed consent prior to any study procedures. Exclusion Criteria: Subjects with increased BG concentration, but without a known history of diabetes (stress hyperglycemia). Subjects treated with diet alone (no antidiabetic agents) and admission HbA1c <7%. Subjects with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria. Patients treated with degludec or glargine U300, or with long-acting weekly GLP1-RA (weekly exenatide, dulaglutide or albiglutide). Patients with history of clinically relevant hepatic disease (diagnosed liver cirrhosis and portal hypertension), ongoing corticosteroid therapy (equal to a prednisone dose ≥5 mg/day), or impaired renal function (eGFR< 30 ml/min), or congestive heart failure (NYHA- IV). Patients with medical and surgical pancreatic disease. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. Known or suspected allergy to trial medication(s), excipients, or related products. Sample size calculation Noninferiority for the primary end point of glycemic control was defined as a mean blood glucose difference of <18 mg/dL between degludec and glargine U300. A blood glucose difference of such a magnitude has been reported in other superiority trials as nonclinically significant and is smaller than significant treatment effects. Assuming the true blood glucose difference between the treatment groups is zero, and using one-sided, two-sample t tests, we required 90 subjects for each treatment group to achieve 90% power. Accounting for a 10% attrition rate, we aimed to enrol 220 subjects in total to achieve >90% power. Interventions Experimental: Degludec Study participants with type 2 diabetes undergoing coronary artery bypass graft (CABG) surgery will receive 100% of the total daily dose (TDD) given as a basal bolus regimen with degludec once daily plus rapid-acting insulin glulisine before meals. Degludec insulin 100 Units/mL, average dose: 30-40 U/day. Insulin Glulisine, 100 Units/mL, average dose: 20-40 U/day. Drug: Degludec Degludec is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. Patients will be treated with bolus regimen given half of total daily dose (TDD) as basal once daily and half as glulisine divided in three equal doses before meals. Patients with poor oral intake or with medical instruction to withhold oral intake (NPO) will receive the basal dose, but prandial dose will be held. Insulin dose will be adjusted daily to maintain a fasting and pre-dinner BG between 100 mg/dl and 180 mg/dl. Drug: Rapid-acting insulin Rapid-acting insulin will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, aspart insulin dose will be held. Active Comparator: Glargine U300 Study participants with type 2 diabetes undergoing CABG surgery will receive 100% of the total daily dose (TDD) given as basal bolus regimen with glargine U300 once daily plus rapid-acting insulin glulisine before meals. Insulin glargine (U300), 300 Units/mL, average dose: 30-40 U/day. Rapid-acting insulin glulisine, 100 Units/mL, average dose: 20-40 U/day. Drug: Glargine (U300) Glargine U300 is a long-acting human insulin analog indicated to improve glycemic control in adults with diabetes mellitus. Patients will be treated with bolus regimen given half of total daily dose (TDD) as basal once daily and half as insulin glulisine divided in three equal doses before meals. Patients with poor oral intake or with medical instruction to withhold oral intake (NPO) will receive the basal dose, but prandial dose will be held. Insulin dose will be adjusted daily to maintain a fasting and pre-dinner BG between 100 mg/dl and 180 mg/dl. Drug: Rapid-acting insulin glulisine Glulisine insulin will be given in three equally divided doses before each meal. To prevent hypoglycemia, if a subject is not able to eat, glulisine insulin dose will be held. Glucose monitoring Glucose levels will be assessed by capillary point-of-care (POC) testing before meals, bedtime and at 3:00 am. A subgroup of participants (n = 100) will be monitored with a professional (blinded) Abbott FreeStyle Libre continuous glucose monitoring (CGM).

Official Title
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Insulin Degludec Versus Glargine U300 for the Management of Hospitalized Patients With Type 2 Diabetes: Randomized Controlled Trial

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Degludec
* Drug: Glargine U300


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females 30 years or above admitted to the hospital for elective CABG surgery A known history of type 2 diabetes treated with any combination of oral antidiabetic agents, short-acting GLP1-RA (exenatide, liraglutide) or insulin therapy except for degludec and glargine U300. Study participants must have a randomization total daily dose (TDD) insulin requirement of at least 20 units per day. Signed, informed consent prior to any study procedures. Exclusion Criteria: Subjects with increased BG concentration, but without a known history of diabetes (stress hyperglycemia). Subjects treated with diet alone (no antidiabetic agents) and admission HbA1c <7%. Subjects with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria. Patients treated with degludec or glargine U300, or with long-acting weekly GLP1-RA (weekly exenatide, or dulaglutide). Patients with history of clinically relevant hepatic disease (diagnosed liver cirrhosis and portal hypertension), ongoing corticosteroid therapy (equal to a prednisone dose ≥5 mg/day), or impaired renal function (eGFR< 30 ml/min), or congestive heart failure (NYHA- IV). Patients with medical and surgical pancreatic disease. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. Known or suspected allergy to trial medication(s), excipients, or related products.

Ages Eligible for Study
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Minimum Age: 30 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: Degludec<br>Study participants with type 2 diabetes undergoing elective coronary artery bypass graft (CABG) surgery will receive 100% of the total daily dose (TDD) given as a basal bolus regimen with degludec once daily plus rapid-acting insulin glulisine before meals. Degludec insulin 100 Units/mL, average dose: 30-40 U/day; Insulin glulisine 100 Units/mL, average dose: 20-40 U/day | Drug: Degludec<br>* Treatment with insulin degludec when compared to insulin glargine U-300 will result in similar blood glucose control in hospitalized patients with type 2 diabetes.<br>|
| Active Comparator: Glargine U300<br>Study participants with type 2 diabetes undergoing CABG surgery will receive 100% of the total daily dose (TDD) given as a basal bolus regimen with glargine U300 once daily plus rapid-acting insulin glulisine before meals. Glargine U300;300 Units/mL, average dose: 30-40 U/day; Insulin glulisine 100 Units/mL, average dose: 20-40 U/day | Drug: Glargine U300<br>* Treatment with insulin glargine U300 when compared to insulin degludec will result in similar blood glucose control in hospitalized patients with type 2 diabetes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in mean daily blood glucose concentration in hospitalized patients | Blood glucose will be measured before each meal, bedtime and at 3:00 am. Mean daily blood glucose concentration will be calculated to determine differences in inpatient glycemic control in patients with type 2 diabetes treated with basal bolus regimen or basal plus regimen with insulin degludec or glargine U-300 once daily plus aspart insulin before meals. | The first 7 days of therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of basic glucose readings between 70 mg/dl and 180 mg/dl before meals in hospitalized patients | Blood glucose will be measured before each meal, bedtime and at 3:00 am, and proportion of basic glucose readings between 70 mg/dl and 180 mg/dl will be recorded. | The first 7 days of therapy | 
| Number of hypoglycemic episodes (BG < 70 mg/dl and 54 mg/dl) in hospitalized patients | Blood glucose will be measured before each meal, bedtime and 3:00 am, and number of hypoglycemic episodes (< 70 mg/dl and 54 mg/dl) will be recorded | The first 7 days of therapy | 
| Number of severe hypoglycemia (< 54 mg/dl) episodes in hospitalized patients | Blood glucose will be measured before each meal, bedtime and at 3:00 am, and number of hypoglycemia (< 54 mg/dl) episodes will be recorded | The first 7 days of therapy | 
| Number of episodes of severe hyperglycemia (BG > 240 mg/dl) in hospitalized patients | Blood glucose will be measured before each meal, bedtime and at 3:00 am, and number of severe hyperglycemia (> 240 mg/dl) episodes will be recorded | The first 7 days of therapy | 
| Daily dose of basal insulin, daily dose of prandial insulin, and total daily dose in hospitalized patients | The study team will document day and time of insulin administration of study drug given once daily and prandial- rapid-acting insulin (aspart) given before meals. The study team will also record dose and number of units given as supplement (correction) to correct hyperglycemia | The first 7 days of therapy | 
| Average blood glucose (mg/dL), percentage time in target, percentage time below target, and percentage time above target in a subgroup of study participants. | A subgroup of participants (n = 100) will be monitored using continuous glucose monitoring system (CGMS) (FreeStyle Libre). | The first 7 days of therapy |