Trial Outcomes & Findings for QT Interval Abnormalities in Sulfonylurea Treated Type 2 Diabetes: Relationship to Treatment Induced Hypoglycaemia (NCT NCT02298803)
NCT ID: NCT02298803
Last Updated: 2018-02-28
Results Overview
The nocturnal time period for the study spanned from 11 pm in the evening until 7 am the following morning on two consecutive days. The change in the corrected QT interval during nocturnal hypoglycemia was determined by calculating the difference between the average QTc interval length during periods of hypoglycemia (blood glucose level \<3.5 mmol/L) and the average QTc interval length during periods of normoglycemia (blood glucose level \>3.5 mmol/L) for the nocturnal time period. The average QTc interval was calculated using an individually optimised correction formula. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was positive, the participant experienced QTc prolongation during hypoglycemia. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was negative, the participant experienced QTc shortening during hypoglycemia.
COMPLETED
NA
30 participants
Nocturnal time period (2300-0700) during the 48 hours of Holter monitoring
2018-02-28
Participant Flow
Patients with type 2 diabetes attending the Diabetes Centre, Royal Prince Alfred Hospital who fulfilled the entry criteria were approached to participate. The requirements of the study were discussed and participants were given a copy of the Participant Information Sheet and Consent Form to read. 30 individuals were recruited in 2015.
30 participants were screened and enrolled. Data from all 30 participants was included in the analysis.
Participant milestones
| Measure |
Holter and Glucose Monitoring
In this study all participants underwent simultaneous monitoring of glucose and QT interval via a subcutaneous continuous glucose monitor and a Hoter monitor, respectively.
Holter and Glucose monitoring: (i) Continuous Glucose Monitoring A sterile disposable glucose-sensing sensor was inserted into the subcutaneous tissue in the abdomen of the patient. This sensor automatically measured the average glucose concentration in interstitial fluid every 5 minutes. The monitor was worn for 48 hours.
(ii)Holter Monitoring The Holter monitor was worn for the same period as the continuous glucose monitor. QT intervals were extracted using proprietary software. Study participants were encouraged to perform regular daily activities during monitoring.
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|---|---|
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Overall Study
STARTED
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30
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Overall Study
COMPLETED
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30
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Overall Study
NOT COMPLETED
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0
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Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Males and Females analysed separately
Baseline characteristics by cohort
| Measure |
Hypoglycemic Group
n=9 Participants
N=9; these participants experienced at least one episode of hypoglycaemia (blood glucose level \<3.5mmol/L) during the monitoring period.
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Normoglycemic Group
n=21 Participants
N=21; these participants experienced no episodes of hypoglycaemia during the monitoring period.
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Total
n=30 Participants
Total of all reporting groups
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|---|---|---|---|
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Age, Continuous
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62.8 years
STANDARD_DEVIATION 10.2 • n=9 Participants
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68.3 years
STANDARD_DEVIATION 7.4 • n=21 Participants
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66.7 years
STANDARD_DEVIATION 8.6 • n=30 Participants
|
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Sex: Female, Male
Female
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3 Participants
n=9 Participants
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9 Participants
n=21 Participants
|
12 Participants
n=30 Participants
|
|
Sex: Female, Male
Male
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6 Participants
n=9 Participants
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12 Participants
n=21 Participants
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18 Participants
n=30 Participants
|
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Region of Enrollment
Australia
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9 participants
n=9 Participants
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21 participants
n=21 Participants
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30 participants
n=30 Participants
|
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Ethnicity: Caucasian, Non-Caucasian
Caucasian
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7 Participants
n=9 Participants
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17 Participants
n=21 Participants
|
24 Participants
n=30 Participants
|
|
Ethnicity: Caucasian, Non-Caucasian
Non-Caucasian
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2 Participants
n=9 Participants
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4 Participants
n=21 Participants
|
6 Participants
n=30 Participants
|
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Diabetes duration
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15.0 years
n=9 Participants
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14.0 years
n=21 Participants
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14.5 years
n=30 Participants
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Diabetes Treatment: Mono or dual therapy, Triple or quadruple therapy
Mono or dual therapy
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5 Participants
n=9 Participants
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9 Participants
n=21 Participants
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14 Participants
n=30 Participants
|
|
Diabetes Treatment: Mono or dual therapy, Triple or quadruple therapy
Triple or quadruple therapy
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4 Participants
n=9 Participants
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12 Participants
n=21 Participants
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16 Participants
n=30 Participants
|
|
HbA1c
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6.6 %
STANDARD_DEVIATION 0.8 • n=9 Participants
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7.0 %
STANDARD_DEVIATION 0.9 • n=21 Participants
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6.9 %
STANDARD_DEVIATION 0.9 • n=30 Participants
|
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Body Mass Index
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31.8 kg/m2
STANDARD_DEVIATION 6.3 • n=9 Participants
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31.2 kg/m2
STANDARD_DEVIATION 5.0 • n=21 Participants
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31.3 kg/m2
STANDARD_DEVIATION 5.4 • n=30 Participants
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Waist circumference
Male
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113 cm
STANDARD_DEVIATION 13 • n=6 Participants • Males and Females analysed separately
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107 cm
STANDARD_DEVIATION 11 • n=12 Participants • Males and Females analysed separately
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109 cm
STANDARD_DEVIATION 13 • n=18 Participants • Males and Females analysed separately
|
|
Waist circumference
Female
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108 cm
STANDARD_DEVIATION 10 • n=3 Participants • Males and Females analysed separately
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108 cm
STANDARD_DEVIATION 11 • n=9 Participants • Males and Females analysed separately
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108 cm
STANDARD_DEVIATION 10 • n=12 Participants • Males and Females analysed separately
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Systolic Blood Pressure
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122 mmHg
STANDARD_DEVIATION 10 • n=9 Participants
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131 mmHg
STANDARD_DEVIATION 10 • n=21 Participants
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128 mmHg
STANDARD_DEVIATION 11 • n=30 Participants
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Smoking Status: Current, Former, Lifelong non-smoker
Current
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2 Participants
n=9 Participants
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0 Participants
n=21 Participants
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2 Participants
n=30 Participants
|
|
Smoking Status: Current, Former, Lifelong non-smoker
Former
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4 Participants
n=9 Participants
|
6 Participants
n=21 Participants
|
10 Participants
n=30 Participants
|
|
Smoking Status: Current, Former, Lifelong non-smoker
Lifelong non-smoker
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3 Participants
n=9 Participants
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15 Participants
n=21 Participants
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18 Participants
n=30 Participants
|
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Alcohol consumption status: Consumer, Abstainer
Consumer
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5 Participants
n=9 Participants
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17 Participants
n=21 Participants
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22 Participants
n=30 Participants
|
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Alcohol consumption status: Consumer, Abstainer
Abstainer
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4 Participants
n=9 Participants
|
4 Participants
n=21 Participants
|
8 Participants
n=30 Participants
|
|
Microvascular Complication Status: Present, Absent
Present
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1 Participants
n=9 Participants
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8 Participants
n=21 Participants
|
9 Participants
n=30 Participants
|
|
Microvascular Complication Status: Present, Absent
Absent
|
8 Participants
n=9 Participants
|
13 Participants
n=21 Participants
|
21 Participants
n=30 Participants
|
PRIMARY outcome
Timeframe: Nocturnal time period (2300-0700) during the 48 hours of Holter monitoringThe nocturnal time period for the study spanned from 11 pm in the evening until 7 am the following morning on two consecutive days. The change in the corrected QT interval during nocturnal hypoglycemia was determined by calculating the difference between the average QTc interval length during periods of hypoglycemia (blood glucose level \<3.5 mmol/L) and the average QTc interval length during periods of normoglycemia (blood glucose level \>3.5 mmol/L) for the nocturnal time period. The average QTc interval was calculated using an individually optimised correction formula. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was positive, the participant experienced QTc prolongation during hypoglycemia. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was negative, the participant experienced QTc shortening during hypoglycemia.
Outcome measures
| Measure |
Hypoglycemia Group
n=8 Participants
While there were nine study participants who experienced hypoglycemia during the entire study period, only eight of those participants experienced hypoglycemia during the nocturnal time period (2300-0700). Six study participants experienced isolated nocturnal hypoglycemia; two study participants experienced both nocturnal and day time hypoglycemia. Hypoglycemia during monitoring was defined as a blood glucose level \<3.5mmol/L that was sustained for a minimum of 20 consecutive minutes.
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|---|---|
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Change in the Corrected QT-interval During Nocturnal Hypoglycemia
QTc shortening during hypoglycemia
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5 Participants
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Change in the Corrected QT-interval During Nocturnal Hypoglycemia
QTc prolongation during hypoglycemia
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3 Participants
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PRIMARY outcome
Timeframe: Day time period (0700-2300) during the 48 hours of Holter monitoringThe day time period for the study spanned from 7 am in the morning until 11 pm in the evening on two consecutive days. The change in the corrected QT interval during day time hypoglycemia was determined by calculating the difference between the average QTc interval length during periods of hypoglycemia (blood glucose level \<3.5 mmol/L) and the average QTc interval length during periods of normoglycemia (blood glucose level \>3.5 mmol/L) for the day time period. The average QTc interval was calculated using an individually optimised correction formula. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was positive, the participant experienced QTc prolongation during hypoglycemia. If the result of average QTc (hypoglycemia) - average QTc (normoglycemia) was negative, the participant experienced QTc shortening during hypoglycemia.
Outcome measures
| Measure |
Hypoglycemia Group
n=3 Participants
While there were nine study participants who experienced hypoglycemia during the entire study period, only eight of those participants experienced hypoglycemia during the nocturnal time period (2300-0700). Six study participants experienced isolated nocturnal hypoglycemia; two study participants experienced both nocturnal and day time hypoglycemia. Hypoglycemia during monitoring was defined as a blood glucose level \<3.5mmol/L that was sustained for a minimum of 20 consecutive minutes.
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|---|---|
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Change in Corrected QT Interval During Day Time Hypoglycaemia
Experienced QTc prolongation during hypoglycemia
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2 Participants
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Change in Corrected QT Interval During Day Time Hypoglycaemia
Experienced QTc shortening during hypoglycemia
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1 Participants
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SECONDARY outcome
Timeframe: Nocturnal time period (2300-0700) during the 48 hours of Holter monitoringPopulation: The eight study participants who experienced nocturnal hypoglycemia are included in the analysis population.
MAGE, a commonly used index of glucose variability, was calculated using data obtained during continuous glucose monitoring. Analysis of correlation between MAGE and delta QTc was undertaken. Please note delta QTc represents the difference between average QTc length during hypoglycemia and average QTc length during normoglycemia.
Outcome measures
| Measure |
Hypoglycemia Group
n=8 Participants
While there were nine study participants who experienced hypoglycemia during the entire study period, only eight of those participants experienced hypoglycemia during the nocturnal time period (2300-0700). Six study participants experienced isolated nocturnal hypoglycemia; two study participants experienced both nocturnal and day time hypoglycemia. Hypoglycemia during monitoring was defined as a blood glucose level \<3.5mmol/L that was sustained for a minimum of 20 consecutive minutes.
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|---|---|
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Pearson's Correlation Coefficient of Delta QTc and a Measure of Glucose Variability, MAGE (Mean Amplitude of Glycemic Excursion).
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0.09 Correlation coefficient
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SECONDARY outcome
Timeframe: 48 hours of continuous glucose monitoringPopulation: Only those participants who experienced nocturnal hypoglycemia (BGL \<3.5 mmol/L for \>20 minutes) are included in the analysis population
The MAGE results (in mmol/L) for the eight participants who experienced nocturnal hypoglycemia are included in the table below.
Outcome measures
| Measure |
Hypoglycemia Group
n=8 Participants
While there were nine study participants who experienced hypoglycemia during the entire study period, only eight of those participants experienced hypoglycemia during the nocturnal time period (2300-0700). Six study participants experienced isolated nocturnal hypoglycemia; two study participants experienced both nocturnal and day time hypoglycemia. Hypoglycemia during monitoring was defined as a blood glucose level \<3.5mmol/L that was sustained for a minimum of 20 consecutive minutes.
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|---|---|
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Mean Amplitude of Glycemic Excursion (MAGE)
Participant 1
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3.9 mmol/L
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Mean Amplitude of Glycemic Excursion (MAGE)
Participant 24
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4.3 mmol/L
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Mean Amplitude of Glycemic Excursion (MAGE)
Participant 4
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4.7 mmol/L
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Mean Amplitude of Glycemic Excursion (MAGE)
Participant 5
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3.0 mmol/L
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Mean Amplitude of Glycemic Excursion (MAGE)
Participant 10
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3.9 mmol/L
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Mean Amplitude of Glycemic Excursion (MAGE)
Participant 15
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1.8 mmol/L
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Mean Amplitude of Glycemic Excursion (MAGE)
Participant 16
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3.6 mmol/L
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Mean Amplitude of Glycemic Excursion (MAGE)
Participant 19
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5.7 mmol/L
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SECONDARY outcome
Timeframe: Nocturnal time period (2300-0700) during the 48 hours of Holter monitoringdeltaQTc is the difference in QTc observed during periods of hypoglycemia and periods of normoglycemia (for those participants who experienced nocturnal hypoglycemia)
Outcome measures
| Measure |
Hypoglycemia Group
n=8 Participants
While there were nine study participants who experienced hypoglycemia during the entire study period, only eight of those participants experienced hypoglycemia during the nocturnal time period (2300-0700). Six study participants experienced isolated nocturnal hypoglycemia; two study participants experienced both nocturnal and day time hypoglycemia. Hypoglycemia during monitoring was defined as a blood glucose level \<3.5mmol/L that was sustained for a minimum of 20 consecutive minutes.
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|---|---|
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deltaQTc
Participant 1
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10 milliseconds
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deltaQTc
Participant 4
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4 milliseconds
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deltaQTc
Participant 5
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-2 milliseconds
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deltaQTc
Participant 10
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-6 milliseconds
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deltaQTc
Participant 15
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-4 milliseconds
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deltaQTc
Participant 16
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-1 milliseconds
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deltaQTc
Participant 19
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-8 milliseconds
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deltaQTc
Participant 24
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15 milliseconds
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Adverse Events
Hypoglycemic Group
Normoglycemic Group
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Hypoglycemic Group
n=9 participants at risk
N=9; these participants experienced at least one episode of hypoglycaemia (blood glucose level \<3.5mmol/L) during the monitoring period.
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Normoglycemic Group
n=21 participants at risk
N=21; these participants experienced no episodes of hypoglycaemia during the monitoring period.
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|---|---|---|
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Endocrine disorders
Hypoglycemia
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100.0%
9/9 • Number of events 15
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0.00%
0/21
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Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place