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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-005334-37 | EudraCT Number |
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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in HbA1c From Baseline to End | A change between two time points is reported. Time Frame: baseline and 12 weeks. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks) | Patients will be instructed to record all insulin injections and a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) during a one-week prestudy run-in period to confirm compliance and document current metabolic control and doses of premixed insulin. Patients will be asked to record not only glucose profiles (at least 4 measurements per day) but also the occurrence of hypoglycemic symptoms or other adverse effects daily throughout the study. During the last week of the study patients will be asked to again record a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) and drug injections to confirm compliance and document metabolic control. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Michael Krebs, MD, Prof. | Medical University of Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medical University Of Vienna, Department of Internal Medicine III | Vienna | State of Vienna | 1090 | Austria |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28357772 | Derived | 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. |
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2 patients declined to participate because of time restraints, thus study medication was administered in 9 patients
11 patients were screened
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| ID | Title | Description |
|---|---|---|
| FG000 | Lixisenatide With Basal Insulin (LixiBIT) | Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide 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. 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Lixisenatide With Basal Insulin (LixiBIT) | Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in HbA1c From Baseline to End | A change between two time points is reported. Time Frame: baseline and 12 weeks. | Posted | Mean | Standard Deviation | HbA1c in percent | 12 weeks |
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Lixisenatide With Basal Insulin (LixiBIT) | Type 2 diabetic patients will be included to perform in this study and will be switched from premixed insulin to insulin glargine and lixisenatide |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| elective ENT surgery | Surgical and medical procedures |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| mild asymptomatic hypoglycaemia | Endocrine disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Prof. Dr. Michael Krebs | Medical University Vienna, Austria | + 43 1 40400 | 43120 | michael.krebs@meduniwien.ac.at |
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| ID | Term |
|---|---|
| D003924 | Diabetes Mellitus, Type 2 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C479460 | lixisenatide |
| D000069036 | Insulin Glargine |
| ID | Term |
|---|---|
| D049528 | Insulin, Long-Acting |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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|
|
| 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. |
|
|
| 12 weeks |
| Change in Body Weight From Baseline to End of Study | A change between two time points is reported. Time Frame: baseline and 12 weeks. | 12 weeks |
| years |
|
| Sex: Female, Male | Count of Participants | Participants | No |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
|
|
| Secondary | Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks) | Patients will be instructed to record all insulin injections and a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) during a one-week prestudy run-in period to confirm compliance and document current metabolic control and doses of premixed insulin. Patients will be asked to record not only glucose profiles (at least 4 measurements per day) but also the occurrence of hypoglycemic symptoms or other adverse effects daily throughout the study. During the last week of the study patients will be asked to again record a complete 7-point-blood glucose profile (fasting, 2h after breakfast, before lunch, 2h after lunch, before dinner, 2h after dinner, late before going to bed) and drug injections to confirm compliance and document metabolic control. | Posted | Mean | 95% Confidence Interval | glucose in mg/dl | 12 weeks |
|
|
|
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| Secondary | Change in Body Weight From Baseline to End of Study | A change between two time points is reported. Time Frame: baseline and 12 weeks. | Posted | Mean | Standard Deviation | weight in kg | 12 weeks |
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| 1 |
| 9 |
| 3 |
| 9 |
| mild gastrointestinal complaints | Gastrointestinal disorders |
|
| urinary tract infection | Infections and infestations |
|
| symptomatic hypoglycaemia | Endocrine disorders |
|
| hypercholesterolaemia | Endocrine disorders |
|
| haematuria | Renal and urinary disorders |
|
| cough | General disorders |
|
| shoulder pain | Musculoskeletal and connective tissue disorders |
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| elective ambulatory cataract surgery | Eye disorders |
|
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| D004700 | Endocrine System Diseases |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |