Trial Outcomes & Findings for Continuous Glucose Monitoring Evaluation of Exenatide Twice Daily Versus Insulin Glargine (NCT NCT01089569)

NCT ID: NCT01089569

Last Updated: 2017-05-23

Results Overview

Measure the changes in HbA1C attributable to exenatide, insulin glargine and their combination. Employ CGM with AGP analysis to determine if there is an incremental benefit for subjects who do not reach target to add exenatide to insulin glargine or insulin glargine to exenatide in patients taking metformin.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

60 participants

Primary outcome timeframe

baseline to final visit (32 weeks)

Results posted on

2017-05-23

Participant Flow

Participant milestones

Participant milestones
Measure
Exenatide
5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Overall Study
STARTED
20
20
20
Overall Study
COMPLETED
16
17
16
Overall Study
NOT COMPLETED
4
3
4

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Continuous Glucose Monitoring Evaluation of Exenatide Twice Daily Versus Insulin Glargine

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Exenatide
n=16 Participants
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study Exenatide: refer to Arm detail
Insulin Glargine
n=17 Participants
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results Insulin Glargine: refer to Arm detail
Exenatide + Insulin Glargine
n=16 Participants
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Total
n=49 Participants
Total of all reporting groups
Age, Continuous
58.6 years
STANDARD_DEVIATION 7.8 • n=5 Participants
53.8 years
STANDARD_DEVIATION 7.4 • n=7 Participants
56.7 years
STANDARD_DEVIATION 8.7 • n=5 Participants
56.3 years
STANDARD_DEVIATION 8.0 • n=4 Participants
Sex: Female, Male
Female
6 Participants
n=5 Participants
10 Participants
n=7 Participants
7 Participants
n=5 Participants
23 Participants
n=4 Participants
Sex: Female, Male
Male
10 Participants
n=5 Participants
7 Participants
n=7 Participants
9 Participants
n=5 Participants
26 Participants
n=4 Participants
Region of Enrollment
United States
16 Participants
n=5 Participants
17 Participants
n=7 Participants
16 Participants
n=5 Participants
49 Participants
n=4 Participants

PRIMARY outcome

Timeframe: baseline to final visit (32 weeks)

Measure the changes in HbA1C attributable to exenatide, insulin glargine and their combination. Employ CGM with AGP analysis to determine if there is an incremental benefit for subjects who do not reach target to add exenatide to insulin glargine or insulin glargine to exenatide in patients taking metformin.

Outcome measures

Outcome measures
Measure
Exenatide
n=16 Participants
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine
n=17 Participants
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine
n=16 Participants
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
HbA1c Change
Baseline
6.4 %HbA1c
Standard Deviation 0.3
6.4 %HbA1c
Standard Deviation 0.5
6.2 %HbA1c
Standard Deviation 0.5
HbA1c Change
Final - Week 32
7.8 %HbA1c
Standard Deviation .6
7.6 %HbA1c
Standard Deviation .5
7.6 %HbA1c
Standard Deviation .7

SECONDARY outcome

Timeframe: baseline to final visit (32 weeks)

Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- iv. Incidence of hypoglycemia (frequency) Change from baseline was calculated as mean incidence rate at baseline minus mean incidence rate at final visit (32 weeks)

Outcome measures

Outcome measures
Measure
Exenatide
n=16 Participants
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine
n=17 Participants
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine
n=16 Participants
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Change From Baseline in Incidence of Hypoglycemia (Frequency)
.7 episodes/day
Standard Deviation 0.8
.8 episodes/day
Standard Deviation 0.8
.6 episodes/day
Standard Deviation 0.4

SECONDARY outcome

Timeframe: baseline to final visit (32 weeks)

Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- iv. Incidence of hypoglycemia (degree) Change from baseline was calculated as mean incidence percentage at baseline minus mean incidence percentage at final visit (32 weeks)

Outcome measures

Outcome measures
Measure
Exenatide
n=16 Participants
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine
n=17 Participants
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine
n=16 Participants
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Change From Baseline in Incidence of Hypoglycemia (Degree)
1.7 percentage of measures under 70 mg/dL
Standard Deviation 2.7
1.7 percentage of measures under 70 mg/dL
Standard Deviation 1.8
1.3 percentage of measures under 70 mg/dL
Standard Deviation 1.1

SECONDARY outcome

Timeframe: baseline to final visit (32 weeks)

Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves iii. Glucose stability (absolute hourly rate of change in median curve) Change from baseline was calculated as mean absolute hourly rate of change in median curve at baseline minus rate at final visit (32 weeks). Mean absolute hourly rate of change in the smoothed median curve is calculated as delta subscript MC = (\|p subscript 50 zero - p subscript 50 23\|+Sum superscript 23 subscript i = 1\| p subscript 50i - p subscript 50 i-1\| over T. i = hour of day p subscript 50i = smoothed 50th percentile value for ith hour of day T = total # of non-missing hourly smoothed percentiles

Outcome measures

Outcome measures
Measure
Exenatide
n=16 Participants
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine
n=17 Participants
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine
n=16 Participants
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Change From Baseline in Glucose Stability (Absolute Hourly Rate of Change in Median Curve)
-2 mg/dL/hr
Standard Deviation 2.7
-2.9 mg/dL/hr
Standard Deviation 4.4
-2 mg/dL/hr
Standard Deviation 3.5

SECONDARY outcome

Timeframe: baseline to final visit (32 weeks)

Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- ii. Glucose variability (inter-quartile range) IQR is the difference between the 75th and 25th percentiles. Change from baseline was calculated as IQR at baseline minus IQR value at final visit (32 weeks).

Outcome measures

Outcome measures
Measure
Exenatide
n=16 Participants
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine
n=17 Participants
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine
n=16 Participants
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Change From Baseline in CGM Glucose Variability
-9 mg/dL
Standard Deviation 9.1
-7.7 mg/dL
Standard Deviation 19.4
-12.1 mg/dL
Standard Deviation 14

SECONDARY outcome

Timeframe: baseline - final visit (32 weeks)

Employ Continuous Glucose Monitoring (CGM) with Ambulatory Glucose Profile (AGP) analysis to characterize the diurnal patterns produced by oral medications (metformin) used in the treatment of type 2 diabetes. Employ CGM to measure the effect of exenatide, insulin glargine and exenatide plus insulin glargine in terms of underlying physiological defects and alter medications in a manner that improves- i. Glucose exposure (area under the diurnal median curve) Change from baseline was calculated as area under the diurnal median curve at baseline minus AUC value at final visit (32 weeks). AUC is calculated using modified rectangle method AUC = sum of superscript 23, subscript i=0 P subscript 50i I = hour of day P subscript 50i = smoother 50th percentile value for ith hour of day

Outcome measures

Outcome measures
Measure
Exenatide
n=16 Participants
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine
n=17 Participants
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine
n=16 Participants
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Change From Baseline in Glucose Exposure (Area Under the Diurnal Median Curve or AUC)
-1207.1 mg/dL*24hr
Standard Deviation 661.1
-1476.2 mg/dL*24hr
Standard Deviation 849.2
-1315 mg/dL*24hr
Standard Deviation 953.9

SECONDARY outcome

Timeframe: baseline - final visit (32 weeks)

Measure the changes in weight attributable to exenatide, insulin glargine and their combinations. Employ CGM with AGP analysis to determine if there is an incremental benefit for subjects who do not reach target to add exenatide to insulin glargine or insulin glargine to exenatide in patients taking metformin. Change from baseline was calculated as weight in pounds at baseline minus weight in pounds at final visit (32 weeks).

Outcome measures

Outcome measures
Measure
Exenatide
n=16 Participants
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study
Insulin Glargine
n=17 Participants
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Exenatide + Insulin Glargine
n=16 Participants
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Change From Baseline in Weight Changes
-13.5 lbs (pounds)
Standard Deviation 10.2
-0.5 lbs (pounds)
Standard Deviation 7.7
-10.3 lbs (pounds)
Standard Deviation 10.5

Adverse Events

Exenatide

Serious events: 0 serious events
Other events: 20 other events
Deaths: 0 deaths

Insulin Glargine

Serious events: 0 serious events
Other events: 10 other events
Deaths: 0 deaths

Exenatide + Insulin Glargine

Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Exenatide
n=20 participants at risk
5 mcg BID for 1 month increasing to 10 mcg BID for the remainder of the study Exenatide: refer to Arm detail
Insulin Glargine
n=20 participants at risk
.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results Insulin Glargine: refer to Arm detail
Exenatide + Insulin Glargine
n=20 participants at risk
Exenatide: 5 mcg BID (twice daily) for 1 month increasing to 10 mcg BID for the remainder of the study \+ Insulin Glargine: 0.1 unit per kg to start, titrated based on Continuous Glucose Monitoring results
Gastrointestinal disorders
nausea and vomiting
85.0%
17/20 • Number of events 17 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
0.00%
0/20 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
0.00%
0/20 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
Immune system disorders
Allergic reaction
5.0%
1/20 • Number of events 1 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
0.00%
0/20 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
0.00%
0/20 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
Skin and subcutaneous tissue disorders
Itching
0.00%
0/20 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
5.0%
1/20 • Number of events 1 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
0.00%
0/20 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
Gastrointestinal disorders
diarrhea
10.0%
2/20 • Number of events 2 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
0.00%
0/20 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
0.00%
0/20 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
Endocrine disorders
Hypoglycemia
20.0%
4/20 • Number of events 14 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
45.0%
9/20 • Number of events 24 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial
65.0%
13/20 • Number of events 26 • Adverse Events were collected for the 32 weeks subjects actively enrolled in trial

Additional Information

Dr. Richard M. Bergenstal

International Diabetes Center

Phone: 952-993-1913

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place