Feasibility of Once/Daily Administered GLP/1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin
Condition: Type 2 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2
Intervention: Lixisenatide; Insulin glargine
Intervention description: Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist.; Patients will be switched to basal insulin glargine (Lantus, once daily in the morning) and GLP-1 receptor agonist Lixisenatide (Lyxumia, once daily in the morning before breakfast; days 1-14 10 µg thereafter 20 µg). The (mean) daily dose of premixed insulin will be calculated based on the records of the run in period. The initial dose of insulin glargine will be adjusted at about 60% of the daily insulin dose of premixed insulin. This is based on the observed reduction of required insulin dose described in recent literature upon initiation with a GLP-1 agonist.
Intervention MeSH terms: Insulin Glargine; Lixisenatide
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No

Summary:

      Premixed insulin-based therapy is a standard insulin treatment strategy in Austria. The
      widespread use of premixed insulin is explained by high acceptance by health care
      professionals and patients due to one single product and flexible number of injections (1-3
      daily) which covers the demand in controlling fasting and postprandial glucose excursions of
      most patients with diabetes. However, the use of pre-mixed insulin frequently leads to a high
      insulin demand and consequently weight gain and an increased risk of hypoglycemia. Hence,
      achieve good metabolic control in these patients remains a major challenge.

      For those patients, the approach to treatment intensification without facing the typical
      risks of insulin treatment (hypoglycemia and weight increase) is of major importance. One, so
      far not exploited option may be the BIT-strategy: Basal insulin in combination with
      incretin-based therapy.

      Pathophysiologically basal insulin inhibits glucose production in the liver, decreases
      hepatic insulin resistance and improves the function of beta cells in the postprandial state
      by discharge of fasting insulin secretion. During further diabetes progression steadily
      increasing HbA1c levels - despite good fasting blood glucose control - indicate the need for
      additional intervention of meal-related glucose excursions. In this stage of type-2 diabetes
      basal insulin can be combined with prandial (short-acting) insulin or prandial GLP-1 receptor
      agonists. However, regarding important safety parameters: risks of hypoglycemia and weight
      gain in the long-term treatment GLP-1 receptor agonists are beneficial.

      Lixisenatide is a novel GLP-1 receptor agonist with a pronounced postprandial (PPG) effect
      which fits with basal insulin mode of action primarily focused on fasting blood glucose
      reduction.

      Therefore 10 patients (both gender) under treatment with premixed insulin (2-3 times daily)
      and HbA1c>7% will be switched to basal insulin glargine (Lantus, once daily) and GLP-1
      receptor agonist Lixisenatide (Lyxumia, once daily). The investigators hypothesize that
      switching from a therapy based on premixed insulin to a simple, once daily administered
      combination of basal insulin plus a GLP-1 receptor agonist in patients with type-2 diabetes
      not achieving therapeutic target (HbA1c>7%) is clinically feasable in an out patient setting
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18 - 70a

          -  Subjects understand study related activities and give written informed concent

          -  HbA1c between 7 - 10 % under treatment with premixed insulin (2-3 injections)

        Exclusion Criteria:

          -  Females of child-bearing age

          -  History of hypoglycemia unawareness

          -  Gastrointestinal disease associated with prolonged nausea and vomiting

          -  Impaired liver function (transaminase >2x than normal)

          -  Impaired kidney function (creatinin > 1,2 mg/dl)

          -  Known intolerance against GLP-1 receptor agonists

          -  History of pancreatitis or pancreas tumor

          -  Malignancies, autoimmune diseases

          -  Severe dyslipidemia (serum triglycerides > 400 mg/dl, cholesterol > 300 mg/dl)

          -  Psychiatric disorder

          -  Oral glucose lowering medication except for metformin