Type 2 Diabetes Mellitus
Conditions
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
Interventions
DRUGLixisenatide
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.
DRUGInsulin 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.
Sponsors
Medical University of Vienna
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c From Baseline to End | 12 weeks | A change between two time points is reported. Time Frame: baseline and 12 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks) | 12 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. |
| Change in Body Weight From Baseline to End of Study | 12 weeks | A change between two time points is reported. Time Frame: baseline and 12 weeks. |
Countries
Austria
Participant flow
Recruitment details
11 patients were screened
Pre-assignment details
2 patients declined to participate because of time restraints, thus study medication was administered in 9 patients
Participants by arm
| Arm | Count |
|---|---|
| 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 | 9 |
| Total | 9 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Lixisenatide With Basal Insulin (LixiBIT) |
|---|---|
| Age, Continuous | 65.6 years STANDARD_DEVIATION 6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Region of Enrollment Austria | 9 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 9 |
| serious Total, serious adverse events | 1 / 9 |
Outcome results
Primary
Change in HbA1c From Baseline to End
A change between two time points is reported. Time Frame: baseline and 12 weeks.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide With Basal Insulin (LixiBIT) | Change in HbA1c From Baseline to End | -0.54 HbA1c in percent | Standard Deviation 0.52 |
p-value: <0.02paired t test
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lixisenatide With Basal Insulin (LixiBIT) | Change in Body Weight From Baseline to End of Study | -1.4 weight in kg | Standard Deviation 3.6 |
p-value: 0.28paired t test
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Lixisenatide With Basal Insulin (LixiBIT) | Change in Fasting Plasma Glucose (FPG, Mean Over 2 Weeks) | -9 glucose in mg/dl |
p-value: 0.24paired t test