Liraglutide in the Treatment of Type 1 Diabetes Mellitus
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Intervention: Liraglutide; Placebo
Intervention description: Patients randomized to 1.2 mg of liraglutide : They will start liraglutide 0.6 mg sc once daily for one week and will increase the dose to 1.2 mg sc once daily thereafter.
Patients randomized to 1.8 mg of liraglutide: They will start liraglutide 0.6 mg sc once daily for one week; will increase to 1.2 mg sc once daily for second week and will stay on 1.8 mg of liraglutide from third week onwards.; Patients randomized to 1.2 mg of placebo: They will start placebo 0.6 mg sc once daily for one week and then increase to 1.2 mg once daily thereafter.
Patients randomized to 1.8 mg of placebo: They will start placebo 0.6 mg sc once daily for one week; increase to 1.2 mg sc once daily for second week and then to 1.8 mg sc once daily from third week onwards.
Intervention MeSH terms: Liraglutide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 72.0
Sex: Female
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Liraglutide; Glucagon; Systolic blood pressure; Weight; Carbohydrate intake; Insulin dose; HbA1c; Post-prandial glucagon

Summary:

      Hypothesis 1: Treatment with Liraglutide in patients with type 1 diabetes decreases fasting,
      postprandial and the overall mean glucose concentrations.

      Aim 1.1: To compare the mean fasting, the mean weekly glucose and the standard deviation of
      weekly blood glucose concentrations as recorded by continuous glucose monitoring prior to and
      following 6 weeks and 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. In
      addition, the time spent at glucose concentrations >150 and 200mg/dl and <70 and <40 mg/dl
      will also be compared.

      Aim 1.2: To compare the postprandial glucose concentrations following a test meal before and
      after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily. Glucose
      concentrations will be measured as areas under the curve for the data obtained from the meal
      challenge.

      Aim 1.3: To compare HbA1c levels(glycated hemoglobin) before and after 12 weeks of treatment
      with 0.6, 1.2 and 1.8 mg of liraglutide daily Hypothesis 2: Treatment with Liraglutide in
      patients with type 1 diabetes decreases postprandial glucagon concentrations and increases
      postprandial C-peptide concentrations.

      Aim 2.1: To compare fasting and postprandial glucagon and C-peptide concentrations following
      a test meal before and after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide
      daily.

      Hypothesis 3: Treatment with Liraglutide in patients with type 1 diabetes delays gastric
      emptying.

      Aim 3.1: To compare the gastric emptying as measured by acetaminophen absorption before and
      after 12 weeks of treatment with 0.6, 1.2 and 1.8 mg of liraglutide daily.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with type 1 diabetes mellitus: Fasting c-peptide < 0.1nmol/l on insulin
             therapy for more than 12 months with or without history of diabetic ketoacidosis.

          2. Using a continuous glucose monitoring device (CGM) and regularly measuring their blood
             sugars four times daily

          3. HbA1c of less than 8.5%.

          4. Well versed with carbohydrate counting

          5. Age 18-75 years

        Exclusion Criteria:

          1. Type 1 diabetes for less than 12 months;

          2. Coronary event or procedure (myocardial infarction, unstable angina, coronary artery
             bypass, surgery or coronary angioplasty) in the previous four weeks;

          3. Hepatic disease (transaminase > 3 times normal) or cirrhosis;

          4. Renal impairment (serum creatinine > 1.5);

          5. HIV or Hepatitis C positive status;

          6. Participation in any other concurrent clinical trial;

          7. Any other life-threatening, non-cardiac disease;

          8. Use of an investigational agent or therapeutic regimen within 30 days of study.

          9. history of pancreatitis

         10. pregnancy

         11. inability to give informed consent

         12. history of gastroparesis

         13. history of medullary thyroid carcinoma or MEN 2 syndrome.

         14. Family history of MEN 2, Family history of medullary thyroid cancer, or familial
             medullary thyroid cancer

         15. Women of childbearing potential who are not using adequate contraception 16) Women who
             are pregnant