Clinical trial NCT01919489: Liraglutide Hospital Discharge Trial
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes
Keywords: Incretins
Liraglutide
Glargine
Randomized controlled trial
basal insulin
hospital discharge
inpatient diabetes
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Novo Nordisk A/S
First posted: 2013-08-09
Enrollment: 273
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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).
2. Admission HbA1c between 7% and 10%
3. 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.
4. 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).
5. BMI \> 25 Kg/m2 and ≤ 45 Kg/m2

Exclusion Criteria:

1. Age \< 18 or \> 80 years.
2. Subjects with stress hyperglycemia (BG \> 140 mg/dL and HbA1c \< 6.5%)
3. Subjects with a history of type 1 diabetes
4. Treatment with insulin or GLP-1 analogs during the past 3 months prior to admission.
5. Recurrent severe hypoglycemia or hypoglycemic unawareness.
6. Subjects with gastrointestinal obstruction, gastroparesis, or those expected to require gastrointestinal suction.
7. History of medullary thyroid cancer or multiple endocrine neoplasias
8. Patients with acute or chronic pancreatitis, pancreatic cancer, or gallbladder disease.
9. 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).
10. Treatment with oral or injectable corticosteroid (equivalent or higher than prednisone 5mg/day), parenteral nutrition, and immunosuppressive treatment.
11. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
12. Female subjects who are pregnant or breastfeeding at the time of enrollment into the study.
13. Females of childbearing potential who are not using adequate contraceptive methods (as required by local law or practice).

Primary outcomes:
measure: Glycemic Control at Hospital Discharge and 6 Months Follow up
timeFrame: Hospital discharge, 6 months (26 weeks)
Secondary outcomes:
measure: Fasting and Postprandial Blood Glucose (BG) Concentration After Follow up of 26 Weeks
timeFrame: After discharge, average at 3 months (12 week) and 6 months (26 weeks)
measure: Hypoglycemic Episodes
timeFrame: After discharge, average 6 months
measure: HbA1c <7.0% and no Hypoglycemia
timeFrame: After discharge, average 6 months
measure: HbA1c <7.0% and no Weight Gain
timeFrame: After discharge, average 6 months
measure: HbA1c <7.0% and no Hypoglycemia
timeFrame: After discharge, average 12 weeks
measure: Change in Body Weight From Baseline
timeFrame: After discharge, average 6 months
measure: Change in BMI
timeFrame: Baseline, and follow up after discharge (average 6 months)
measure: Total Daily Dose of Insulin
timeFrame: After discharge, average 6 months
measure: Change in Cardiovascular Risk Factors: Blood Pressure
timeFrame: Baseline, 26 weeks post-intervention
measure: Cardiovascular Risk Factor: Heart Rate
timeFrame: 26 weeks post-intervention
measure: Cardiovascular Risk Factor: Lipid Profile
timeFrame: 26 weeks post-intervention
measure: Emergency Room Visits and Readmissions
timeFrame: After discharge, average 6 months
measure: Acute Renal Failure
timeFrame: After discharge, average 6 months
measure: Self-measured Blood Glucose (SMBG) 7-point Profiles at 26 Weeks Follow up
timeFrame: 26 weeks post-intervention
Other outcomes:
Locations:
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory Universtiy Hospital at MIdtown
state: Georgia
city: New York
country: United States
facility: State University of NY at Buffalo
state: New York
Study officials:
affiliation: Emory University SOM
name: Guillermo E Umpierrez, MD
role: PRINCIPAL_INVESTIGATOR
References: