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Liraglutide Hospital Discharge Trial

Phase 4
Completed
Conditions
Type 2 Diabetes
Interventions
Drug: Liraglutide + OADs
Drug: Glargine + OADs
Registration Number
NCT01919489
Lead Sponsor
Emory University
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
273
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
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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).
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Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Liraglutide + OADsLiraglutide + OADsLiraglutide once daily in combination to oral anti-diabetic agents (OADs)
Glargine + OADsGlargine + OADsGlargine once daily in combination to oral anti-diabetic agents (OADs)
Primary Outcome Measures
NameTimeMethod
Glycemic Control at Hospital Discharge and 6 Months Follow upHospital discharge, 6 months (26 weeks)

To determine differences in HbA1c concentration at 26 weeks from discharge between liraglutide and glargine insulin therapy

Secondary Outcome Measures
NameTimeMethod
Cardiovascular Risk Factor: Lipid Profile26 weeks post-intervention

Lipid profile was measured with total cholesterol level results at 26 weeks post-intervention. This outcome was not part of standard of care.

Emergency Room Visits and ReadmissionsAfter discharge, average 6 months

Number of participants who had at least one emergency room visit and hospital readmissions

Acute Renal FailureAfter discharge, average 6 months

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)

Fasting and Postprandial Blood Glucose (BG) Concentration After Follow up of 26 WeeksAfter discharge, average at 3 months (12 week) and 6 months (26 weeks)

To determine differences in BG concentration between liraglutide and glargine insulin therapy

Hypoglycemic EpisodesAfter discharge, average 6 months

Number of participants who had at least one hypoglycemic event (\<70 mg/dl) and severe hypoglycemic event (\<40 mg/dl)

HbA1c <7.0% and no Weight GainAfter discharge, average 6 months

Percent of patients with 26 week HbA1c \<7.0% and no weight gain

Change in Cardiovascular Risk Factors: Blood PressureBaseline, 26 weeks post-intervention

Cardiovascular risk factors including changes in systolic and diastolic blood pressure from baseline to 26 weeks post-intervention

HbA1c <7.0% and no HypoglycemiaAfter discharge, average 12 weeks

Percent of patients with 12 week HbA1c \<7.0% and no hypoglycemia

Change in Body Weight From BaselineAfter discharge, average 6 months

Change in body weight from baseline after 6 months of follow up (26 weeks)

Change in BMIBaseline, and follow up after discharge (average 6 months)

Change in BMI after 6 months from baseline

Total Daily Dose of InsulinAfter discharge, average 6 months

Evaluate the total daily dose of insulin needed in the group receiving glargine

Cardiovascular Risk Factor: Heart Rate26 weeks post-intervention

Cardiovascular risk: heart rate at baseline and 26 weeks post-intervention

Self-measured Blood Glucose (SMBG) 7-point Profiles at 26 Weeks Follow up26 weeks post-intervention

Number of participants that reported self-measured blood glucose (SMBG) 7-point profiles at 26 weeks follow up

Trial Locations

Locations (5)

Emory Universtiy Hospital at MIdtown

🇺🇸

Atlanta, Georgia, United States

University of Miami

🇺🇸

Miami, Florida, United States

Grady Memorial Hospital

🇺🇸

Atlanta, Georgia, United States

Emory University Hospital

🇺🇸

Atlanta, Georgia, United States

State University of NY at Buffalo

🇺🇸

New York, New York, United States

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