Adding Liraglutide to High Dose Insulin: Breaking the Cycle

Obesity Clinical Trial

Official title:

Adding Liraglutide to High Dose Insulin: Breaking the Cycle

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01505673
• Other study ID #: IIS-000235
• Status: Completed
• Phase: Phase 4
• First received: January 4, 2012
• Last updated: December 15, 2017
• Start date: January 2012
• Est. completion date: June 2016

Study information

• Verified date: December 2017
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate whether the addition of liraglutide 1.8 mg/day to a high-dose insulin regimen (>1.8 units/kg/day) in patients with uncontrolled (HbA1c >7.5%) type 2 diabetes mellitus will improve blood sugar control.

It also evaluates the effect of liraglutide on liver and pancreatic fat content, explores the mechanism of blood sugar improvement by assessing weight and pancreatic hormone release, and assesses blood pressure, lipid profile, and liver function. Finally it will look at patient quality of life and safety.

Description:

Type 2 diabetes is a progressive disease with incessant beta-cell dysfunction that often ultimately requires insulin treatment. Patients requiring high insulin dosages represent a particular treatment challenge and often have uncontrolled glycemia despite progressive dose increases and are especially prone to insulin related lipotoxicity and weight gain.

Glucagon-like peptide agonists (GLP-1) such as liraglutide have many actions that position them to break the vicious cycle in this population through the following mechanisms: (1) weight loss; (2) improved hepatic steatosis; (3) improved pancreatic steatosis; (4) decreased glucagon levels; (5) improved beta-cell function.

The purpose of the study is to demonstrate that liraglutide is both effective and safe when added to a high dose insulin treatment regimen. Liraglutide will improve glycemic control, weight, metabolic parameters, as well as patient satisfaction, with minimal adverse events. The study also proposes to study the mechanisms through which such improvements might occur, especially beta-cell function, glucagon levels, and hepatic and pancreatic fat content.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 71
• Est. completion date: June 2016
• Est. primary completion date: June 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Type 2 diabetes mellitus

• Insulin dose of >1.8 units/kg/day (represents total daily insulin dose, regardless of formulation, regimen, number of daily shots)

• HbA1c = 7.5% and = 11%

• Age = 18

• Stable comorbidities on stable treatment regimens

• Stable dose of all oral hypoglycemics for = 3 months prior to enrollment

• Ability to provide informed consent before any trial-related activities

Exclusion Criteria:

• Type 1 diabetes mellitus

• Any contraindication to the MRI procedure (metallic implants, severe claustrophobia, pregnancy, unable to lie still on a hard table for the duration of the procedure, weight above 400 lb - limit of the MRI table, magnet's inner circumference smaller than the largest body circumference)

• History of any pancreatic disease as it might interfere with the pancreatic TG measurement (i.e. pancreatitis, tumors, cysts, type 1 diabetes, any pancreatic surgery)

• End Stage Renal Disease on dialysis due to increased risk of hypoglycemia, and possible interference with accurate measurement of HbA1c

• Incretin therapy (any GLP-1 agonist or DPP-IV inhibitor)

• Unstable or decompensated comorbidities

• Personal or family history of medullary thyroid carcinoma or MEN-2 syndrome

• Severe gastroparesis

• Pregnancy, breast feeding, intention to become pregnant, or not using adequate contraceptive measures

• Organ transplant recipient or waiting list candidate

• Steroid use (current or potential use during the trial)

• Known/suspected allergy to trial medication, excipients, or related products

• Contraindications to study medications, worded specifically as stated in the product's prescribing information

• Non-English speaking volunteers since no interpreters are available and the safety of the volunteers could be jeopardized if adequate and reliable communication is not possible.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity
• Type 2 Diabetes Mellitus

Intervention

Drug:
• Liraglutide
Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months
• Saline
Placebo injection of 1.8mg saline once daily for 6-months

Locations

Country	Name	City	State
United States	UT Southwestern	Dallas	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Ildiko Lingvay	Novo Nordisk A/S

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic Control Measured by HbA1c	HbA1c (%)	6-months
Secondary	Pancreatic and Hepatic Triglyceride Content	Liver Triglyceride and Pancreatic Triglyceride	6-months
Secondary	Weight		6-months
Secondary	Beta-Cell Function	Fasting Glucose as a Measure of Beta-Cell Function	6-months
Secondary	Glucagon	Measured during mixed meal challenge test.	6-months
Secondary	Total Daily Insulin Dose	The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month.	6-months
Secondary	Number of Daily Injections	The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month.	6-months
Secondary	Blood Pressure		6-months
Secondary	Lipid Profile		6-months
Secondary	Liver Function Blood Test		6-months
Secondary	Hypoglycemic Events	Reported as hypoglycemic events per month by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl	6-months
Secondary	Quality of Life Survey (QoL) - General Health Perception	General health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 = excellent; 2 = very good; 3 = good; 4 = fair; 5 = poor.	6-months
Secondary	Beta-Cell Function	Fasting C-peptide as a Measure of Beta-Cell Function	6 months
Secondary	Matsuda Index as a Measure of Beta Cell Function	The Matsuda index is a measure of insulin sensitivity and has no minimum/maximum values. Index values are calculated as 500,000/square root of ((fasting glucose x fasting c-peptide x 333) x (mean 120 min post-meal glucose x mean 120 min post-meal c-peptide x 333)). Higher/lower values = better/worse insulin sensitivity.	6 months
Secondary	Beta-cell Function	AUC c-peptide	6 Months
Secondary	Ratio (AUC C-peptide/AUC Glucose)		6 months
Secondary	AUC Glucose		6 months
Secondary	Quality of Life Survey (QoL) - Current Health Perception	Current health perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago.	6 months
Secondary	Quality of Life Survey (QoL) - Treatment Satisfaction	Quality of Life Survey (QoL) - treatment satisfactionTreatment satisfaction was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.	6 months
Secondary	Quality of Life Survey (QoL) - Treatment Impact	Treatment impact was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.	6 months
Secondary	Quality of Life Survey (QoL) - Social or Vocational Worry	Social or vocational worry was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time.	6 months
Secondary	Quality of Life Survey (QoL) - Hypoglycemia Fear	Hypoglycemia fear was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry.	6 months
Secondary	Quality of Life Survey (QoL) - Glycemia Control Perception	Glycemia control perception was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled.	6 months
Secondary	Quality of Life Survey (QoL) - Lifestyle Flexibility	Lifestyle flexibility was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice.	6 months
Secondary	Quality of Life Survey (QoL) - Social Stigma	Social stigma was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1 strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree.	6 months
Secondary	Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment	Satisfaction with insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied.	6 months
Secondary	Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment	Willingness to continue insulin treatment was measured at randomization and 6 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing.	6 months