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Completed

NCT Number: NCT01505673

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.

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Key information

Conditions

Type 2 Diabetes Mellitus Body Weight Diabetes Mellitus Diabetes Mellitus, Type 2 Digestive System Diseases Endocrine System Diseases Fatty Liver Glucose Metabolism Disorders Hyperinsulinism Insulin Resistance Liver Diseases Metabolic Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

UT Southwestern

Dallas, Texas, 75390, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

liraglutide

Drug

Liraglutdie 1.8mg injected subcutaneously from pen device once daily for 6-months

Other names: Victoza

Saline

Drug

Placebo injection of 1.8mg saline once daily for 6-months

Primary outcomes

  1. Glycemic Control Measured by HbA1c

    Time frame: 6-months

    HbA1c (%)

Secondary outcomes

  1. Pancreatic and Hepatic Triglyceride Content

    Time frame: 6-months

    Liver Triglyceride and Pancreatic Triglyceride

  2. Weight

    Time frame: 6-months

  3. Beta-Cell Function

    Time frame: 6-months

    Fasting Glucose as a Measure of Beta-Cell Function

  4. Glucagon

    Time frame: 6-months

    Measured during mixed meal challenge test.

  5. Total Daily Insulin Dose

    Time frame: 6-months

    The 3 days average of the total daily dose of insulin used within 3 consecutive days prior office visit 6 month.

  6. Number of Daily Injections

    Time frame: 6-months

    The 3 days average of the number of daily injections performed within 3 consecutive days prior office visit 6 month.

  7. Blood Pressure

    Time frame: 6-months

  8. Lipid Profile

    Time frame: 6-months

  9. Liver Function Blood Test

    Time frame: 6-months

  10. Hypoglycemic Events

    Time frame: 6-months

    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

  11. Quality of Life Survey (QoL) - General Health Perception

    Time frame: 6-months

    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.

  12. Beta-Cell Function

    Time frame: 6 months

    Fasting C-peptide as a Measure of Beta-Cell Function

  13. Matsuda Index as a Measure of Beta Cell Function

    Time frame: 6 months

    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.

  14. Beta-cell Function

    Time frame: 6 Months

    AUC c-peptide

  15. Ratio (AUC C-peptide/AUC Glucose)

    Time frame: 6 months

  16. AUC Glucose

    Time frame: 6 months

  17. Quality of Life Survey (QoL) - Current Health Perception

    Time frame: 6 months

    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.

  18. Quality of Life Survey (QoL) - Treatment Satisfaction

    Time frame: 6 months

    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.

  19. Quality of Life Survey (QoL) - Treatment Impact

    Time frame: 6 months

    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.

  20. Quality of Life Survey (QoL) - Social or Vocational Worry

    Time frame: 6 months

    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.

  21. Quality of Life Survey (QoL) - Hypoglycemia Fear

    Time frame: 6 months

    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.

  22. Quality of Life Survey (QoL) - Glycemia Control Perception

    Time frame: 6 months

    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.

  23. Quality of Life Survey (QoL) - Lifestyle Flexibility

    Time frame: 6 months

    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.

  24. Quality of Life Survey (QoL) - Social Stigma

    Time frame: 6 months

    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.

  25. Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment

    Time frame: 6 months

    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.

  26. Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment

    Time frame: 6 months

    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.

Sponsors and collaborators

Lead sponsor

Ildiko Lingvay

Other

Collaborators

  • Novo Nordisk A/S

Registry information

Important dates

Study start
2012
Primary completion
2016
Study completion
2016
First posted
Jan 6, 2012
Registry last updated
Jan 16, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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