Adding Liraglutide to High Dose Insulin: Breaking the Cycle
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.
|Type 2 Diabetes Mellitus Obesity||Drug: Liraglutide Drug: Saline||Phase 4|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
|Official Title:||Adding Liraglutide to High Dose Insulin: Breaking the Cycle|
- Glycemic control measured by HbA1c [ Time Frame: 2-months and 6-months ]
- Pancreatic and Hepatic triglyceride content [ Time Frame: 6-months ]Magnetic Resonance Spectroscopy scan of liver and pancreas
- Weight [ Time Frame: 1-, 2-, 4-, and 6-months ]
- Beta-Cell Function [ Time Frame: 6-months ]Mixed Meal Challenge Test over 4 hours measuring glucose, c-peptide, and insulin. Then C-peptide area under the curve (AUC)and change in c-peptide over change in glucose will be calculated.
- Glucagon [ Time Frame: 6-months ]Measured during mixed meal challenge test.
- Total Daily Insulin Dose [ Time Frame: 1-, 2-, 4-, and 6-months ]Calculated at each visit by summing all insulin shots of all types over a 24 hrs period. The average of the 3 most recent 24 hrs prior to each visit will be used.
- Number of daily injections [ Time Frame: 1-, 2-, 4-, and 6-months ]Counted by adding all shots regardless of the type of insulin. The average of the 3 most recent 24 hrs prior to each visit will be used.
- Blood Pressure [ Time Frame: 1-, 2-, 4-, and 6-months ]
- Lipid Profile [ Time Frame: 1-, 2-, 4-, and 6-months ]
- Liver Function blood test [ Time Frame: 1-, 2-, 4-, and 6-months ]
- Hypoglycemic Events [ Time Frame: 3-, 7-, 14-days and 1-, 2-, 4-, and 6-months ]Reported by patient as any blood glucose <70 mg/dl or symptoms of hypoglycemia with blood glucose >70 mg/dl
- Quality of Life Survey [ Time Frame: 6-months ]
|Study Start Date:||January 2012|
|Study Completion Date:||June 2016|
|Primary Completion Date:||June 2016 (Final data collection date for primary outcome measure)|
|Active Comparator: Liraglutide||
Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months
Other Name: Victoza
|Placebo Comparator: Saline injection||
Placebo injection of 1.8mg saline once daily for 6-months
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01505673
|United States, Texas|
|Dallas, Texas, United States, 75390|
|Principal Investigator:||Ildiko Lingvay, MD||UT Southwestern|