Feasibility of Once/Daily Administered GLP/1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin

NCT ID: NCT02168491

Last Updated: 2017-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-11-30
• Study Completion Date: 2015-08-31

Brief 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

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intervention group

10 type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide

Group Type: EXPERIMENTAL

Lixisenatide

Intervention Type: DRUG

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.

Insulin glargine

Intervention Type: DRUG

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.

Interventions

Lixisenatide

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 Type: DRUG

Insulin glargine

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 Type: DRUG

Other Intervention Names

Lyxumia; Lantus

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Prof. Dr. Michael Krebs

Prof. MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Krebs, MD, Prof.

Role: PRINCIPAL_INVESTIGATOR

Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria

Locations

Medical University Of Vienna, Department of Internal Medicine III

Vienna, Vienna, Austria

Countries

Austria

References

Harreiter J, Kosi-Trebotic L, Lukas A, Wolf P, Winhofer Y, Luger A, Kautzky-Willer A, Krebs MR. Switch to Combined GLP1 Receptor Agonist Lixisenatide with Basal Insulin Glargine in Poorly Controlled T2DM Patients with Premixed Insulin Therapy: A Clinical Observation and Pilot Study in Nine Patients. Diabetes Ther. 2017 Jun;8(3):683-692. doi: 10.1007/s13300-017-0249-4. Epub 2017 Mar 29.

Reference Type: DERIVED

PMID: 28357772 (View on PubMed)

Other Identifiers

2013-005334-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LixiBIT_V3

Identifier Type: -

Identifier Source: org_study_id