Liraglutide in Type 1 Diabetes

Overweight Clinical Trial

Official title:

Liraglutide in Type 1 Diabetes. A Randomised, Double-blind, Placebo Controlled Study of the Effect of Liraglutide as an Additional Treatment to Insulin on HbA1c, Body Weight and Hypoglycaemia in Poorly Regulated Type 1 Diabetes Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01612468
• Other study ID #: Lira1
• Status: Completed
• Phase: Phase 4
• First received: May 11, 2012
• Last updated: January 26, 2016
• Start date: June 2012
• Est. completion date: February 2015

Study information

• Verified date: January 2016
• Source: Steno Diabetes Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Dataprotection AgencyDenmark: Danish Medicines AgencyDenmark: The Danish National Committee on Biomedical Research Ethics
• Study type: Interventional

Clinical Trial Summary

A randomised, double-blind, placebo controlled study of the effect of liraglutide as an additional treatment to insulin on HbA1c, body weight and hypoglycaemia in poorly regulated type 1 diabetes patients.

Background: Treatment with glucagon-like peptid 1 (GLP-1) agonists liraglutide and exanatide leads to weight loss and decrease in haemoglobin A1c in oral anti diabetic treated type 2 diabetes patients.

It is estimated that 40-50 % of type 1 diabetes patients in the US suffers from overweight or poor glycaemic control (HbA1c > 8 %).

Small studies, not placebo controlled, reports effects of adding liraglutide to a group of well regulated (HbA1c < 7.5 %) normal to overweight insulin treated type 1 diabetes patients for 24 weeks. A decrease in HbA1c, weight, insulin doses and glycaemic excursions measured by continuous glucose monitoring was seen.

Primary objective:To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in HbA1c in patients with type 1 diabetes as an add-on therapy to insulin. Secondary objectives:To investigate the effect of liraglutide as an add-on therapy to insulin compared to placebo on change in:Weight, insulin dose,hypoglycaemic events, CGM, BMI, body composition, quality of life, treatment satisfaction,food preferences, meal test, CIMT, PWV and 24 hour blood pressure.

Description:

A randomised, double-blind, placebo controlled study of the effect of liraglutide as an additional treatment to insulin on HbA1c, body weight and hypoglycaemia in poorly regulated type 1 diabetes patients.

Background Treatment with glucagon-like peptid 1 (GLP-1) agonists liraglutide and exenatide leads to weight loss and decrease in haemoglobin A1c (HbA1c) in oral anti diabetic treated type 2 diabetes patients. Smaller studies have shown similar effects in insulin treated type 2 diabetes patients, with no increased risk of hypoglycaemia.

It is estimated that 40-50 % of type 1 diabetes patients in the US suffers from overweight or poor glycaemic control (HbA1c > 8 %). At present treatment of type 1 diabetes solely consists of insulin injections.

A recent study reports effects of adding liraglutide to a group of well regulated (HbA1c < 7.5 %) normal to overweight insulin treated type 1 diabetes patients for 24 weeks. A decrease in HbA1c, weight, insulin doses and glycaemic excursions measured by continuous glucose monitoring was seen. The study was not placebo controlled.

The available literature suggests that GLP-1 agonists reduce insulin dose and weight in well regulated type 1 diabetes patients, who are normal- to overweight. To our knowledge, no study has addressed whether liraglutide will improve HbA1c and reduce bodyweight in overweight and poorly regulated type 1 diabetes patients.

At present the most efficient way to reduce HbA1c is to use insulin pump therapy, and most studies suggest that this will decreased HbA1c by approximately 0.5 %. Insulin pump therapy is however only an option in very compliant patients. In most clinics treating type 1 diabetes 40-50 % of patients will have HbA1c > 8 % and many of these patients will, due to insufficient compliance, not be candidates for an insulin pump.

At Steno Diabetes Center approximately 3000 well characterized type 1 diabetes patients is followed in the outpatient clinic, and 40-50 % of these have HbA1c > 8.0 %. If liraglutide given once daily results in a reduction of HbA1c of 0.5 % it will probably be a very cost-effective additional therapy for type 1 diabetes patients in insufficient metabolic control.

Several studies have shown that liraglutide lowers systolic blood pressure. Dysregulation increases the risk of microvascular complications in type 1 diabetes of which microalbuminuria results in a need for treatment with antihypertensive medication. Overweight increases the risk of hypertension and arteriosclerosis and thereby cardiovascular diseases. Carotis intima media thickness is a validated estimate for future cardiovascular disease and pulse wave velocity is a measure of arterial stiffness. We perform 24 hour blood pressure measurements to document possible effects of liraglutide on blood pressure and CIMT and PWV to investigate the effect of liraglutide on cardiovascular disease and arteriosclerosis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 100
• Est. completion date: February 2015
• Est. primary completion date: February 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Type 1 diabetes according to WHO criteria = 1 year

• Age = 18 years

• BMI > 25 kg/m2

• HbA1c > 8.0 % at visit 0

Exclusion Criteria:

• Insulin pump treatment

• Hypoglycaemia unawareness (unability to register low blood glucose)

• Diabetic gastroparesis

• Compromised kidney function (eGFR < 60 ml/min/1,73m2), dialysis or kidney transplantation at visit 0

• Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)

• Acute or chronic pancreatitis

• Inflammatory bowel disease

• Cancer unless in complete remission for > 5 years

• History of thyroid adenoma or carcinoma

• Other concomitant disease or treatment that according to the investigator's assessment makes the patient unsuitable for study participation

• Alcohol/drug abuse

• Fertile women not using contraceptives

• Pregnant or nursing women

• Known or suspected hypersensitivity to trial product or related products

• Receipt of an investigational drug within 30 days prior to visit 0

• Simultaneous participation in any other clinical intervention trial

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Overweight

Intervention

Drug:
• Liraglutide
1.8 mg/day subcutaneous
• Placebo
1.8 mg/day subcutaneous

Locations

Country	Name	City	State
Denmark	Steno Diabetes Center	Gentofte

Sponsors (3)

Lead Sponsor	Collaborator
Steno Diabetes Center	University Hospital, Gentofte, Copenhagen, University of Copenhagen

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c	To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in HbA1c in patients with type 1 diabetes as an adjunctive therapy to insulin treatment.	24 week	Yes
Secondary	Body weight	To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in weight, BMI and body composition	24 weeks	Yes
Secondary	Cardiovascular	To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in carotis intima media thickness, pulse wave velocity, 24 hour blood pressure	24 weeks	Yes
Secondary	Standardised liquid meal test	To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in postprandial glucagon levels, glycaemic excursion, gastric emptying, VAS score for appetite and food preference	24 weeks	Yes
Secondary	Glycaemic excursions	To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in insulin dose, hypoglycaemic events and glycaemic excursions (time spent in hypo- and hyperglycaemia as measured by CGM)	24 weeks	Yes
Secondary	Quality of life	To investigate the effect of liraglutide 1.8 mg once daily compared to placebo for 24 weeks on change in quality of life and treatment satisfaction	24 weeks	Yes