Outcome
Type |
Measure |
Description |
Time frame |
Safety issue |
Other |
Measures of beta-cell function using the oral minimal model method calculated using data from the mixed-meal test |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. Measures of beta-cell function will be calculated using the oral minimal model method with data from the mixed-meal test. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Other |
Measures of insulin sensitivity using the oral minimal model method calculated using data from the mixed-meal test |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. Measures of insulin sensitivity will be calculated using the oral minimal model method with data from the mixed-meal test. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Other |
Measures of first-pass hepatic insulin extraction using the oral minimal model method calculated using data from the mixed-meal test |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. Measures of first-pass hepatic insulin extraction will be calculated using the oral minimal model method with data from the mixed-meal test. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Other |
Average daily meal frequency (meals>30g/24h and meals <30g/24h) assessed during the treatment periods |
During the intake of empagliflozin and placebo, participants will report meals in an electronic event diary. Average daily meal frequency per 24 hours will be calculated. |
The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo. |
|
Other |
Total amount of daily excreted glucose (g/24h) measured in the 24h urine collection |
The participants will collect a 24-hours urine sample on the day before the mixed meal test. Total amount of daily excreted glucose (in grams per 24 hours) will be calculated. |
The outcome will be assessed during the day before the experimental visit. |
|
Other |
Glucagon response during the mixed-meal test (incremental AUC from 0 to 120min following meal ingestion) |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the plasma glucagon concentrations will be measured. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Other |
Insulin response during the mixed-meal test (incremental AUC from 0 to 120min following meal ingestion) |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the plasma insulin concentrations will be measured. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Other |
Ketone levels (3-beta-hydroxybutyrate) during the mixed-meal test |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, ketone levels (3-beta-hydroxybutyrate) will be measured. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Primary |
Amplitude of change in plasma glucose (difference between peak and nadir plasma glucose concentration in mmol/L) during the mixed meal test. |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the amplitude of plasma glucose (difference between peak and nadir plasma glucose concentration in mmol/L) will be measured. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Secondary |
Mean amplitude of glucose excursion (MAGE) based on CGM glucose |
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. MAGE will be calculated based on CGM data obtained during each observation period. |
The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded. |
|
Secondary |
Mean coefficient of variability based on CGM glucose |
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. The mean coefficient of variability will be calculated based on CGM data obtained during each observation period. |
The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded. |
|
Secondary |
Peak plasma glucose during mixed meal test |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the peak of plasma glucose (in mmol/L) will be documented. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Secondary |
Percent time spent with CGM glucose >10.0mmol/L |
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. Percent time spent with CGM glucose >10.0mmol/L will be calculated based on CGM data obtained during each observation period. |
The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded. |
|
Secondary |
Proportion of participants experiencing hypoglycaemia (defined as plasma glucose<3.0mmol/L) during the mixed meal tolerance test |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the proportion of participants experiencing hypoglycaemia (defined as plasma glucose<3.0mmol/L) will be documented. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Secondary |
Nadir plasma glucose during mixed meal test |
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the nadir of plasma glucose (in mmol/L) will be documented. |
The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period). |
|
Secondary |
Percent time spent with CGM glucose <3.0mmol/L |
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. Percent time spent with CGM glucose <3.0mmol/L will be calculated based on CGM data obtained during each observation period. |
The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded. |
|
Secondary |
Percent time spent with CGM glucose <2.8mmol/L |
During the intake of empagliflozin and placebo, participants will wear a continuous glucose monitoring device. After V1 and V2, CGM data will be extracted and analysed. Percent time spent with CGM glucose <2.8mmol/L will be calculated based on CGM data obtained during each observation period. |
The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded. |
|
Secondary |
Frequency of postprandial symptoms based on a modified Edinburgh Hypoglycaemia |
During the intake of empagliflozin and placebo, participants will report postprandial symptoms in an electronic event diary. The frequency of postprandial symptoms, based on a modified Edinburgh Hypoglycaemia Symptom Scale, will be documented. |
The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo. |
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