Liraglutide Hospital Discharge Trial

Study Overview
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Brief Summary
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High blood glucose levels in hospitalized patients with diabetes are associated with increased risk of medical complications and death. Improved glucose control with insulin injections may improve clinical outcome and prevent some of the hospital complications. Increasing evidence indicates that incretin-based agents are safe and effective for the hospital management of patients with type 2 diabetes (T2D). Liraglutide is a once-daily human glucagon-like peptide (GLP-1) analogue approved for the treatment of T2D. Liraglutide has been shown to lower blood glucose, stimulate endogenous insulin secretion, decrease plasma glucagon levels, inhibit gastric emptying, reduce food intake and body weight and improve ß-cell function when administered subcutaneously. Liraglutide increases insulin secretion in a glucose-dependent manner (i.e., only when plasma glucose levels are elevated), resulting in low-risk of hypoglycemia when used as monotherapy. When compared to insulin glargine therapy, the use of GLP-1 has resulted in comparable reduction in HbA1c level, lower rates of hypoglycemia and less weight gain. No prospective studies; however, have compared the efficacy and safety of liraglutide in the hospital setting or after hospital discharge. The primary objective is to compare the safety and efficacy of liraglutide (Victoza®) versus glargine insulin in combination to oral anti-diabetic agents (OADs: metformin, sulfonylureas, nateglinide, repaglinide or pioglitazone) on glycemic control after 26 weeks of treatment in medicine patients with T2D after hospital discharge.

Detailed Description
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Specific Aim: To determine whether treatment with liraglutide (Victoza®) will result in similar glycemic control (HbA1c at 26 weeks) and a lower rate of hypoglycemic events compared to treatment with glargine (Lantus®) in patients with T2D after hospital discharge. Patients with poorly controlled (HbA1c >7%-10%) T2D treated with diet or oral antidiabetic agents or low dose insulin naïve (0.4u/kg/day) prior to admission will be randomized to liraglutide or glargine in combination to OADs at hospital discharge.

Official Title
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A Randomized Controlled Trial Comparing the Safety and Efficacy of Liraglutide Versus Glargine Insulin for the Management of Patients With Type 2 Diabetes After Hospital Discharge

Conditions
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Type 2 Diabetes

Intervention / Treatment
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* Drug: Liraglutide + OADs
* Drug: Glargine + OADs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between the ages of 18 and 80 years discharged after hospital admission from non- ICU general surgery and medicine services (excluding gastrointestinal and cardiac surgeries). Admission HbA1c between 7% and 10% Patients with T2D treated with diet alone or with oral antidiabetic agents as monotherapy or in combination therapy (excluding GLP1 receptor agonists) or on low-dose insulin therapy (TDD ≤0.4 unit/kg/day) prior to admission. Subjects with a hospital admission BG < 400 mg/dL without laboratory evidence of diabetic ketoacidosis (serum bicarbonate < 18 mEq/L or positive serum or urinary ketones). BMI > 25 Kg/m2 and ≤ 45 Kg/m2 Exclusion Criteria: Age < 18 or > 80 years. Subjects with stress hyperglycemia (BG > 140 mg/dL and HbA1c < 6.5%) Subjects with a history of type 1 diabetes Treatment with insulin or GLP-1 analogs during the past 3 months prior to admission. Recurrent severe hypoglycemia or hypoglycemic unawareness. Subjects with gastrointestinal obstruction, gastroparesis, or those expected to require gastrointestinal suction. History of medullary thyroid cancer or multiple endocrine neoplasias Patients with acute or chronic pancreatitis, pancreatic cancer, or gallbladder disease. Patients with clinically significant hepatic disease (cirrhosis, jaundice, end-stage liver disease, portal hypertension) and elevated ALT and AST > 3 times upper limit of normal, or significantly impaired renal function (GFR < 30 ml/min). Treatment with oral or injectable corticosteroid (equivalent or higher than prednisone 5mg/day), parenteral nutrition, and immunosuppressive treatment. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study. Female subjects who are pregnant or breastfeeding at the time of enrollment into the study. Females of childbearing potential who are not using adequate contraceptive methods (as required by local law or practice).

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: Liraglutide + OADs<br>Liraglutide once daily in combination to oral anti-diabetic agents (OADs) | Drug: Liraglutide + OADs<br>* Liraglutide subcutaneously daily<br>* Other names: Victoza® + OADs;|
| Active Comparator: Glargine + OADs<br>Glargine once daily in combination to oral anti-diabetic agents (OADs) | Drug: Glargine + OADs<br>* Glargine once daily subcutaneously<br>* Other names: Glargine (Lantus®) + OADs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Control at Hospital Discharge and 6 Months Follow up | To determine differences in HbA1c concentration at 26 weeks from discharge between liraglutide and glargine insulin therapy | Hospital discharge, 6 months (26 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fasting and Postprandial Blood Glucose (BG) Concentration After Follow up of 26 Weeks | To determine differences in BG concentration between liraglutide and glargine insulin therapy | After discharge, average at 3 months (12 week) and 6 months (26 weeks) | 
| Hypoglycemic Episodes | Number of participants who had at least one hypoglycemic event (<70 mg/dl) and severe hypoglycemic event (<40 mg/dl) | After discharge, average 6 months | 
| HbA1c <7.0% and no Hypoglycemia | Percent of patients with 26 week HbA1c <7.0% and no hypoglycemia | After discharge, average 6 months | 
| HbA1c <7.0% and no Weight Gain | Percent of patients with 26 week HbA1c <7.0% and no weight gain | After discharge, average 6 months | 
| HbA1c <7.0% and no Hypoglycemia | Percent of patients with 12 week HbA1c <7.0% and no hypoglycemia | After discharge, average 12 weeks | 
| Change in Body Weight From Baseline | Change in body weight from baseline after 6 months of follow up (26 weeks) | After discharge, average 6 months | 
| Change in BMI | Change in BMI after 6 months from baseline | Baseline, and follow up after discharge (average 6 months) | 
| Total Daily Dose of Insulin | Evaluate the total daily dose of insulin needed in the group receiving glargine | After discharge, average 6 months | 
| Change in Cardiovascular Risk Factors: Blood Pressure | Cardiovascular risk factors including changes in systolic and diastolic blood pressure from baseline to 26 weeks post-intervention | Baseline, 26 weeks post-intervention | 
| Cardiovascular Risk Factor: Heart Rate | Cardiovascular risk: heart rate at baseline and 26 weeks post-intervention | 26 weeks post-intervention | 
| Cardiovascular Risk Factor: Lipid Profile | Lipid profile was measured with total cholesterol level results at 26 weeks post-intervention. This outcome was not part of standard of care. | 26 weeks post-intervention | 
| Emergency Room Visits and Readmissions | Number of participants who had at least one emergency room visit and hospital readmissions | After discharge, average 6 months | 
| Acute Renal Failure | Acute renal failure during the 26-week follow-up defined as a clinical diagnosis of acute renal failure with documented new-onset abnormal renal function (increment in creatinine > 0.5 mg/dL from baseline) | After discharge, average 6 months | 
| Self-measured Blood Glucose (SMBG) 7-point Profiles at 26 Weeks Follow up | Number of participants that reported self-measured blood glucose (SMBG) 7-point profiles at 26 weeks follow up | 26 weeks post-intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Incretins, Liraglutide, Glargine, Randomized controlled trial, basal insulin, hospital discharge, inpatient diabetes