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

NCT02168491 | Completed Phase 3 Results DMC

• 2 other identifiers: LixiBIT_V32013-005334-37
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• Change in HbA1c From Baseline to End

  A change between two time points is reported. Time Frame: baseline and 12 weeks.

  12 weeks

Secondary Outcomes (2)

• Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks)

  12 weeks

• Change in Body Weight From Baseline to End of Study

  12 weeks

Study Arms (1)

Intervention group

EXPERIMENTAL

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

Drug: Lixisenatide; Drug: Insulin glargine

Interventions

Lixisenatide 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.

Also known as: Lyxumia

Intervention group

Insulin glargine 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.

Also known as: Lantus

Intervention group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Medical University of Vienna: lead

Study Sites (1)

Medical University Of Vienna, Department of Internal Medicine III

Vienna, Vienna, 1090, Austria

Location

Related Publications (1)

• 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.

  PMID: 28357772 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

lixisenatide; Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Results Point of Contact

• Title: Prof. Dr. Michael Krebs
• Organization: Medical University Vienna, Austria

michael.krebs@meduniwien.ac.at

+ 43 1 40400

Study Officials

• Michael Krebs, MD, Prof.

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

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. MD

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: June 20, 2014
• Study Start: November 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: August 1, 2015
• Last Updated: May 9, 2017
• Results First Posted: April 4, 2017

Record last verified: 2017-03

Locations

AU (1)