Basal Bolus Versus Basal Insulin in Type 2 Diabetes Mellitus (T2DM)

Study Overview
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Brief Summary
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The study is a prospective randomized study comparing safety and effectiveness of a basal-bolus regimen with glargine once daily and glulisine before meals, a basal plus regimen with glargine once daily and supplemental doses of glulisine, and sliding scale regular insulin (SSI) on correction of insulin regimen for the hospital management of medical and surgical patients with type 2 diabetes.

Detailed Description
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High blood glucose levels in medical and surgery patients with diabetes are associated with increased risk of in-hospital complications and death. Improved glucose control with insulin injections may improve clinical outcome and prevent some of the hospital complications. Numerous studies have shown that high blood glucose increases the risk of wound infection, kidney failure and death. It is not known; however, what is the best insulin regimen in patients who will undergo surgery. The use of repeated injections of regular insulin is commonly used for glucose control in hospitalized patients with diabetes. Recently, the combination of Lantus® and Apidra® insulins has been shown to improve glucose control with lower rate of hypoglycemia (low blood sugar). The investigators' recent preliminary data also indicate that a single daily dose of glargine plus corrective doses of glulisine before meals if needed (Basal Plus) is effective in the management of medical and surgical patients with type 2 diabetes mellitus (T2DM). The average daily blood glucose (BG) levels in patients treated with Basal Plus is equivalent to levels in patients treated with Basal Bolus with glargine once daily plus glulisine before meals (basal bolus regimen). The mean daily BG levels in patients treated with basal plus are lower than those reported in patients treated with sliding scale regular insulin (SSRI). Accordingly, the present study aims to determine which insulin treatment is best for glucose control in hospitalized patients with diabetes admitted to general medicine wards. Glargine, glulisine, and regular insulins are approved for use in the treatment of patients with diabetes by the FDA. A total of 375 subjects with type 2 diabetes will be recruited in this study. The sites for this study are Grady Memorial Hospital, Emory University Hospital, the Atlanta VA Medical Center, Scott & White Memorial Hospital and Clinic, and Medical University of South Carolina.

Official Title
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Basal Bolus Versus Basal Insulin Regimen for the Treatment of Hospitalized Patients With Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes, Hyperglycemia

Intervention / Treatment
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* Drug: sliding scale regular insulin (SSRI)
* Drug: Basal Bolus
* Drug: Basal Plus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between the ages of 18 and 75 years admitted to a general medicine or surgical services. A known history of type 2 diabetes mellitus > 3 months, receiving either diet alone, oral monotherapy, or with any combination of oral antidiabetic agents (sulfonylureas, meglitinides, metformin, thiazolidinediones, dipeptidyl peptidase (DPP) IV inhibitors). Patients admitted for non-cardiac elective or emergency surgery or trauma. Subjects must have an admission BG > 140 mg and < 400 mg/dL without laboratory evidence of diabetic ketoacidosis (bicarbonate < 18 milliequivalent /L, potential hydrogen (pH) < 7.30, or positive serum or urinary ketones). Exclusion Criteria: Subjects with increased blood glucose concentration, but without a known history of diabetes (stress hyperglycemia). Subjects with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria [32]. Patients with acute critical or surgical illness admitted to the ICU or expected to require admission to the ICU. Patients admitted for coronary artery bypass graft (CABG) or patients receiving continuous insulin infusion. Patients with clinically relevant hepatic disease (diagnosed liver cirrhosis and portal hypertension), corticosteroid therapy, or impaired renal function (creatinine ≥ 3.0 mg/dl). Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. Female subjects are pregnant or breast feeding at time of enrollment into the study. Patients with recognized or suspected endocrine disorders associated with increased insulin resistance, acromegaly, or hyperthyroidism. Female subjects are pregnant or breast feeding at time of enrollment into the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Basal Plus Regimen<br>glargine subcutaneously once daily plus corrective doses of glulisine subcutaneously before meals and bedtime as needed | Drug: Basal Plus<br>* glargine once daily plus corrective doses of glulisine before meals and bedtime as needed<br>* Other names: Apidra (insulin glulisine);|
| Experimental: Basal Bolus<br>glargine subcutaneously once daily plus glulisine subcutaneously before meals (plus corrective doses of glulisine as needed) | Drug: Basal Bolus<br>* glargine once daily plus glulisine before meals (plus corrective doses of glulisine as needed)<br>* Other names: Apidra (insulin glulisine);|
| Active Comparator: sliding scale regular insulin (SSRI)<br>sliding scale regular insulin subcutaneously four-times daily in patients with T2DM admitted to general medicine and surgery wards. | Drug: sliding scale regular insulin (SSRI)<br>* four-time daily in patients with T2DM admitted to general medicine and surgery wards.<br>* Other names: Novolin R;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Blood Glucose Levels (Measured in mg/dL) at Randomization Are Compared to Mean Blood Glucose Levels After First Day of Treatment Among Subjects Treated With Basal Plus, Basal -Bolus and SSRI Treatments | The primary outcome is to determine the effective glycemic control among the subjects that received Basal Plus (glargine once daily plus corrective doses of glulisine before meals and bedtime as needed), Basal Bolus approach of glargine once daily plus corrective doses of glulisine before meals and Sliding Scale Regular Insulin (SSRI). Glycemic control is measured by mean blood glucose(BG) levels in mg/dL after first day of treatment and are compared to mean BG levels at randomization among subjects treated with Basal Plus, Basal -bolus and SSRI treatments. The optimal glycemic control is achieved when BG levels are between 70 mg/dL -140 mg/dL. The BG levels levels below 70 mg/dL are regarded as hypoglycemic events. The BG levels levels above 140 mg/dl are considered elevated and Hyperglycemia defined as a fasting BG >126 mg/dl or random BG >200 mg/dl on two or more occasions). | Randomization and 24 hrs after treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Patients With Hypoglycemia Events (Blood Glucose Levels < 70 mg/dL) During Their Hospital Stay That Are Treated With Basal Plus, Basal-bolus and SSRI Treatments | Effective Glycemic control is also assessed by number of hypoglycemia events among the patients treated with Basal plus, basal-bolus and SSRI treatments. Hypoglycemia event is defined as blood glucose levels <70 mg/dL. Number of patients with hypoglycemia episodes that are treated with Basal plus, basal-bolus and SSRI treatment regimens during their hospital stay are examined and compared. | During hospital stay, up to 12 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 Diabetes, Inpatient Hyperglycemia