Liraglutide Hospital Discharge Trial

Type 2 Diabetes Clinical 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01919489
• Other study ID #: IRB00068128
• Secondary ID: (UTN) U1111-1139
• Status: Completed
• Phase: Phase 4
• Start date: March 2014
• Est. completion date: August 30, 2020

Study information

• Verified date: August 2021
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 273
• Est. completion date: August 30, 2020
• Est. primary completion date: August 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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).

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Liraglutide + OADs
Liraglutide subcutaneously daily
• Glargine + OADs
Glargine once daily subcutaneously

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	Emory Universtiy Hospital at MIdtown	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	University of Miami	Miami	Florida
United States	State University of NY at Buffalo	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Emory University	Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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)
Secondary	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
Secondary	HbA1c <7.0% and no Hypoglycemia	Percent of patients with 26 week HbA1c <7.0% and no hypoglycemia	After discharge, average 6 months
Secondary	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
Secondary	HbA1c <7.0% and no Hypoglycemia	Percent of patients with 12 week HbA1c <7.0% and no hypoglycemia	After discharge, average 12 weeks
Secondary	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
Secondary	Change in BMI	Change in BMI after 6 months from baseline	Baseline, and follow up after discharge (average 6 months)
Secondary	Total Daily Dose of Insulin	Evaluate the total daily dose of insulin needed in the group receiving glargine	After discharge, average 6 months
Secondary	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
Secondary	Cardiovascular Risk Factor: Heart Rate	Cardiovascular risk: heart rate at baseline and 26 weeks post-intervention	26 weeks post-intervention
Secondary	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
Secondary	Emergency Room Visits and Readmissions	Number of participants who had at least one emergency room visit and hospital readmissions	After discharge, average 6 months
Secondary	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
Secondary	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