Clinical trial NCT02168491: Feasibility of Once/Daily Administered GLP/1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin
Official title: Feasibility of Once-daily Administered GLP-1 Receptoragonist (Lixisenatide) in Combination With Basal Insulin in Patients With Type-2 Diabetes Mellitus Not Achieving Therapeutic Targets With Premixed Insulin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 2 Diabetes Mellitus
Lead sponsor: Medical University of Vienna
Sponsor class: OTHER
First posted: 2014-06-20
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


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

Primary outcomes:
measure: Change in HbA1c From Baseline to End
timeFrame: 12 weeks
Secondary outcomes:
measure: Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks)
timeFrame: 12 weeks
measure: Change in Body Weight From Baseline to End of Study
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Vienna
country: Austria
facility: Medical University Of Vienna, Department of Internal Medicine III
Study officials:
affiliation: Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
name: Michael Krebs, MD, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.