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Adding Liraglutide to High Dose Insulin: Breaking the Cycle

This study has been completed.
ClinicalTrials.gov Identifier:
First Posted: January 6, 2012
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Novo Nordisk A/S
Information provided by (Responsible Party):
Ildiko Lingvay, University of Texas Southwestern Medical Center

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.

Condition Intervention Phase
Type 2 Diabetes Mellitus Obesity Drug: Liraglutide Drug: Saline Phase 4

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by Ildiko Lingvay, University of Texas Southwestern Medical Center:

Primary Outcome Measures:
  • Glycemic control measured by HbA1c [ Time Frame: 2-months and 6-months ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 98
Study Start Date: January 2012
Study Completion Date: June 2016
Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Liraglutide Drug: Liraglutide
Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months
Other Name: Victoza
Placebo Comparator: Saline injection Drug: Saline
Placebo injection of 1.8mg saline once daily for 6-months

Detailed 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.


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01505673

United States, Texas
UT Southwestern
Dallas, Texas, United States, 75390
Sponsors and Collaborators
Ildiko Lingvay
Novo Nordisk A/S
Principal Investigator: Ildiko Lingvay, MD UT Southwestern
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ildiko Lingvay, Assistant Professor, University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier: NCT01505673     History of Changes
Other Study ID Numbers: IIS-000235
First Submitted: January 4, 2012
First Posted: January 6, 2012
Last Update Posted: November 17, 2017
Last Verified: May 2017

Keywords provided by Ildiko Lingvay, University of Texas Southwestern Medical Center:
Glucagon-like peptide
pancreatic steatosis
hepatic steatosis

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists