Trial Outcomes & Findings for CHOICE: CHanges to Treatment and Outcomes in Patients With Type 2 Diabetes Initiating InjeCtablE Therapy (NCT NCT00635492)

Results Overview

The primary objective of this study is to estimate the time spent on initial treatment regime before significant treatment change for patients with type 2 diabetes initiating therapy with either insulin or exenatide for the first time. Initial treatment regime is defined as the treatment regime prescribed when the patient is enrolled in the study. Significant treatment change for patients initiated on insulin or exenatide is defined as at least one of the following: Insulin: * Addition of a new medication for the treatment of type 2 diabetes * A change in the number of times insulin is administered per day * Discontinuation of any insulin initiated at baseline * Substitution of a human insulin for an analogue insulin or vice-versa. * Switching between brands of the same class/type of insulin is not included in the definition of significant treatment change. Exenatide: * Addition of a new medication for the treatment of type 2 diabetes * Discontinuation of exenatide.

Recruitment status

COMPLETED

Target enrollment

2515 participants

Primary outcome timeframe

Month 24

Results posted on

2015-04-09

Participant Flow

This observational study was conducted at 322 study centers in 6 countries (Belgium, Denmark, France, Germany, Greece, Sweden). Date of first patient enrolled: 25 January 2008 Date of last patient completed: 01 December 2011

2515 patients enrolled. 2388 patients in final analysis (22 not in either cohort), excluded: 92 had no investigator signature on summary page, 11 had no treatment start date, 2 had issues with their informed consent to release their data.

Participant milestones

Participant milestones
Measure	Exenatide BID Daily dose ranging from 5-20 mcg	Insulin Insulin at a dose selected by the health care provided (HCP) and patient
Overall Study STARTED	1114	1274
Overall Study COMPLETED	835	992
Overall Study NOT COMPLETED	279	282

Reasons for withdrawal

Reasons for withdrawal
Measure	Exenatide BID Daily dose ranging from 5-20 mcg	Insulin Insulin at a dose selected by the health care provided (HCP) and patient
Overall Study Death	12	40
Overall Study Lost to Follow-up	151	172
Overall Study Physician Decision	32	22
Overall Study Sponsor decision	2	3
Overall Study Withdrawal by Subject	82	45

Baseline Characteristics

CHOICE: CHanges to Treatment and Outcomes in Patients With Type 2 Diabetes Initiating InjeCtablE Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Exenatide BID n=1114 Participants Daily dose ranging from 5-20 ug	Insulin n=1274 Participants Insulin at a dose selected by the HCP and patient	Total n=2388 Participants Total of all reporting groups
Age, Continuous	58.1 years STANDARD_DEVIATION 10.1 • n=5 Participants	63.7 years STANDARD_DEVIATION 10.9 • n=7 Participants	61.1 years STANDARD_DEVIATION 10.9 • n=5 Participants
Sex: Female, Male Female	516 Participants n=5 Participants	541 Participants n=7 Participants	1057 Participants n=5 Participants
Sex: Female, Male Male	598 Participants n=5 Participants	733 Participants n=7 Participants	1331 Participants n=5 Participants
Region of Enrollment France	168 participants n=5 Participants	84 participants n=7 Participants	252 participants n=5 Participants
Region of Enrollment Greece	319 participants n=5 Participants	488 participants n=7 Participants	807 participants n=5 Participants
Region of Enrollment Denmark	43 participants n=5 Participants	16 participants n=7 Participants	59 participants n=5 Participants
Region of Enrollment Germany	384 participants n=5 Participants	438 participants n=7 Participants	822 participants n=5 Participants
Region of Enrollment Sweden	84 participants n=5 Participants	85 participants n=7 Participants	169 participants n=5 Participants
Region of Enrollment Belgium	116 participants n=5 Participants	163 participants n=7 Participants	279 participants n=5 Participants
Glycosylated hemoglobin (HbA1c)	8.4 percentage of total hemoglobin STANDARD_DEVIATION 1.4 • n=5 Participants	9.2 percentage of total hemoglobin STANDARD_DEVIATION 1.9 • n=7 Participants	8.8 percentage of total hemoglobin STANDARD_DEVIATION 1.7 • n=5 Participants
Body Weight	101.2 kg STANDARD_DEVIATION 21.8 • n=5 Participants	84.2 kg STANDARD_DEVIATION 17.6 • n=7 Participants	92.1 kg STANDARD_DEVIATION 21.4 • n=5 Participants
Body Mass Index (BMI)	35.3 kg/m2 STANDARD_DEVIATION 6.6 • n=5 Participants	29.7 kg/m2 STANDARD_DEVIATION 5.4 • n=7 Participants	32.3 kg/m2 STANDARD_DEVIATION 6.6 • n=5 Participants
Duration of Diabetes	8.2 years STANDARD_DEVIATION 5.7 • n=5 Participants	9.8 years STANDARD_DEVIATION 7.3 • n=7 Participants	9.1 years STANDARD_DEVIATION 6.7 • n=5 Participants
Concomitant Oral Anti-Diabetic Medication No OAD	50 Number of Patients n=5 Participants	154 Number of Patients n=7 Participants	204 Number of Patients n=5 Participants
Concomitant Oral Anti-Diabetic Medication Single OAD	383 Number of Patients n=5 Participants	476 Number of Patients n=7 Participants	859 Number of Patients n=5 Participants
Concomitant Oral Anti-Diabetic Medication Combination of 2 OADs	552 Number of Patients n=5 Participants	523 Number of Patients n=7 Participants	1075 Number of Patients n=5 Participants
Concomitant Oral Anti-Diabetic Medication Combination of 3 OADs	118 Number of Patients n=5 Participants	112 Number of Patients n=7 Participants	230 Number of Patients n=5 Participants
Concomitant Oral Anti-Diabetic Medication Combination of 4 OADs	11 Number of Patients n=5 Participants	9 Number of Patients n=7 Participants	20 Number of Patients n=5 Participants

PRIMARY outcome

Timeframe: Month 24

Population: All patients who provided consent to release information and who fulfil the study entry criteria were included in the analyses. Patients were assigned to the exenatide BID or insulin cohort based the injectable treatment started at baseline; analyses were conducted irrespective of later treatment changes.

The primary objective of this study is to estimate the time spent on initial treatment regime before significant treatment change for patients with type 2 diabetes initiating therapy with either insulin or exenatide for the first time. Initial treatment regime is defined as the treatment regime prescribed when the patient is enrolled in the study. Significant treatment change for patients initiated on insulin or exenatide is defined as at least one of the following: Insulin: * Addition of a new medication for the treatment of type 2 diabetes * A change in the number of times insulin is administered per day * Discontinuation of any insulin initiated at baseline * Substitution of a human insulin for an analogue insulin or vice-versa. * Switching between brands of the same class/type of insulin is not included in the definition of significant treatment change. Exenatide: * Addition of a new medication for the treatment of type 2 diabetes * Discontinuation of exenatide.

Outcome measures

Outcome measures
Measure	Exenatide BID n=1113 Participants daily dose ranging from 5-20mcg/day	Insulin n=1273 Participants insulin at a dose selected by the HCP and patient
Estimates of Probability to Remain on Initial Injectable Treatment at 12 and 24 Months. Estimate at 24 months	53.9 probability (%) 95% Confidence Interval 123 • Interval 50.8 to 57.0	60.6 probability (%) 95% Confidence Interval 123 • Interval 57.7 to 63.5
Estimates of Probability to Remain on Initial Injectable Treatment at 12 and 24 Months. Estimate at 12 months	67.8 probability (%) Interval 65.0 to 70.6	70.6 probability (%) Interval 68.0 to 73.1

SECONDARY outcome

Timeframe: Baseline

Population: All participants who provided consent to release information, fulfilled the study entry criteria, and had a start date provided were included in the analyses.

Higher BMI was one of the Factors evaluated for association with treatment choice at baseline. BMI was calculated as body weight in kilograms (kg) divided by height in meters (m) squared (kg/m\^2). The mean BMI at baseline is provided below and the statistical analysis provides the 2 arms odds ratio for BMI=1 kg/m\^2 higher. Participants were assigned to the exenatide BID or insulin cohort based the injectable treatment started at baseline; analyses were conducted irrespective of later treatment changes. Baseline was Visit T1 (prior to start of treatment).

Outcome measures

Outcome measures
Measure	Exenatide BID n=1177 Participants daily dose ranging from 5-20mcg/day	Insulin n=1315 Participants insulin at a dose selected by the HCP and patient
Higher Body Mass Index (BMI) Associated With Treatment Choice at Baseline	35.3 kg/m^2 Standard Deviation 6.5 • Interval 1.13 to 1.19	29.7 kg/m^2 Standard Deviation 5.4

SECONDARY outcome

Timeframe: Baseline

Population: All participants who provided consent to release information, fulfilled the study entry criteria, and had a start date provided were included in the analyses.

Higher HbA1c was one of the Factors evaluated for association with treatment choice at baseline.HbA1c was reported in percent of hemoglobin. The mean HbA1c at baseline is provided below and the statistical analysis provides the 2 arms odds ratio for HbA1c=1% higher.

Outcome measures

Outcome measures
Measure	Exenatide BID n=1177 Participants daily dose ranging from 5-20mcg/day	Insulin n=1315 Participants insulin at a dose selected by the HCP and patient
Higher Hemoglobin A1c (HbA1) Associated With Treatment Choice at Baseline	8.4 percent of hemoglobin Standard Deviation 1.4	9.2 percent of hemoglobin Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline

Population: All participants who provided consent to release information, fulfilled the study entry criteria, and had a start date provided were included in the analyses.

Older age (1 year older) was one of the Factors evaluated for association with treatment choice at baseline. The mean age at baseline is provided below and the statistical analysis provides the 2 arms odds ratio for age 1 year older. Participants were assigned to the exenatide BID or insulin cohort based the injectable treatment started at baseline; analyses were conducted irrespective of later treatment changes. Baseline was Visit T1 (prior to start of treatment).

Outcome measures

Outcome measures
Measure	Exenatide BID n=1114 Participants daily dose ranging from 5-20mcg/day	Insulin n=1274 Participants insulin at a dose selected by the HCP and patient
Older Age Associated With Treatment Choice at Baseline	58.1 years Standard Deviation 10.1	63.7 years Standard Deviation 10.9

SECONDARY outcome

Timeframe: Baseline

Population: All participants who provided consent to release information, fulfilled the study entry criteria, provided the specific data (DHP-18 subscale on disinhibited eating) and had a start date provided were included in the analyses.

Diabetes Health Profile (DHP-18) - consists of 18 items across 3 domains (psychological distress, barriers to activity, and disinhibited eating), with each item standardized score rated from 0-100; 0=no dysfunction, higher numbers=greater dysfunction. The subscale of disinhibited eating was one of the Factors evaluated for association with treatment choice at baseline. The number of participants with disinhibited eating at baseline is provided below and the statistical analysis provides the 2 arms odds ratio for disinhibited eating. Participants were assigned to the exenatide BID or insulin cohort based the injectable treatment started at baseline; analyses were conducted irrespective of later treatment changes. Baseline was Visit T1 (prior to start of treatment).

Outcome measures

Outcome measures
Measure	Exenatide BID n=386 Participants daily dose ranging from 5-20mcg/day	Insulin n=446 Participants insulin at a dose selected by the HCP and patient
Disinhibited Eating Associated With Treatment Choice at Baseline	43.52 units on a scale Standard Deviation 20.99	34.38 units on a scale Standard Deviation 20.33

SECONDARY outcome

Timeframe: 6 months prior to Baseline

Random Glucose 1 millimole per liter (mmol/L) higher was one of the Factors evaluated for association with treatment choice at baseline. Random glucose is a glucose within the last 6 months prior to baseline. The mean is provided below and the statistical analysis provides the 2 arms odds ratio for the glucose 1 mmol/L higher. Participants were assigned to the exenatide BID or insulin cohort based the injectable treatment started at baseline; analyses were conducted irrespective of later treatment changes. Baseline was Visit T1 (prior to start of treatment).

Outcome measures

Outcome measures
Measure	Exenatide BID n=1177 Participants daily dose ranging from 5-20mcg/day	Insulin n=1315 Participants insulin at a dose selected by the HCP and patient
Higher Random Glucose Associated With Treatment Choice at Baseline	10.37 mmol/L Standard Deviation 3.13	12.13 mmol/L Standard Deviation 4.36

SECONDARY outcome

Timeframe: 4 weeks prior to Baseline

Population: All participants who provided consent to release information, fulfilled the study entry criteria, and had a start date provided were included in the analyses.

Frequent glucose self-testing (1 test/week more) was one of the Factors evaluated for association with treatment choice at baseline. The mean number of self monitoring blood glucose tests per week over the last 4 weeks prior to baseline was determined at baseline and is provided below. The statistical analysis provides the 2 arms odds ratio. Participants were assigned to the exenatide BID or insulin cohort based the injectable treatment started at baseline; analyses were conducted irrespective of later treatment changes. Baseline was Visit T1 (prior to start of treatment).

Outcome measures

Outcome measures
Measure	Exenatide BID n=928 Participants daily dose ranging from 5-20mcg/day	Insulin n=1050 Participants insulin at a dose selected by the HCP and patient
Frequent Blood Glucose Self Monitoring Associated With Treatment Choice at Baseline	9.28 tests/week Standard Deviation 7.98	9.91 tests/week Standard Deviation 8.58

SECONDARY outcome

Timeframe: Baseline

Population: All participants who provided consent to release information, fulfilled the study entry criteria, and had a start date provided were included in the analyses.

Receipt of diet and exercise advice was one of the Factors evaluated for association with treatment choice at baseline. The number of participants who checked yes or no during the baseline visit for prior receipt of diet/exercise advice in his/her Diabetes management is provided below and the statistical analysis provides the 2 arms odds ratio. Participants were assigned to the exenatide BID or insulin cohort based the injectable treatment started at baseline; analyses were conducted irrespective of later treatment changes. Baseline was Visit T1 (prior to start of treatment).

Outcome measures

Outcome measures
Measure	Exenatide BID n=1177 Participants daily dose ranging from 5-20mcg/day	Insulin n=1315 Participants insulin at a dose selected by the HCP and patient
Diet and Exercise Advice in Diabetes Management Associated With Treatment Choice at Baseline Missing	12 participants	1 participants
Diet and Exercise Advice in Diabetes Management Associated With Treatment Choice at Baseline No	131 participants	237 participants
Diet and Exercise Advice in Diabetes Management Associated With Treatment Choice at Baseline Yes	910 participants	905 participants
Diet and Exercise Advice in Diabetes Management Associated With Treatment Choice at Baseline Unknown	124 participants	172 participants

SECONDARY outcome

Timeframe: Baseline

Population: All participants who provided consent to release information, fulfilled the study entry criteria, and had a start date provided were included in the analyses.

Higher (1 mmol/L higher) LDL cholesterol was one of the Factors evaluated for association with treatment choice at baseline. The mean LDL cholesterol at baseline is provided below and the statistical analysis provides the 2 arms odds ratio for 1 mmol/L higher at baseline. Participants were assigned to the exenatide BID or insulin cohort based the injectable treatment started at baseline; analyses were conducted irrespective of later treatment changes. Baseline was Visit T1 (prior to start of treatment).

Outcome measures

Outcome measures
Measure	Exenatide BID n=1177 Participants daily dose ranging from 5-20mcg/day	Insulin n=1315 Participants insulin at a dose selected by the HCP and patient
Higher Value of Low Density Lipoprotein Cholesterol Associated With Treatment Choice at Baseline	2.82 mmol/L Standard Deviation 1.09	3.00 mmol/L Standard Deviation 1.01

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: Patients were assigned to the exenatide BID or insulin cohort based on their initial injectable treatment started at baseline, and analyses were conducted irrespective of later treatment changes. All patients who provided consent to release information and who fulfilled study entry criteria were included in this analysis population.

Changes in HbA1c From Baseline to Month 24

Outcome measures

Outcome measures
Measure	Exenatide BID n=795 Participants daily dose ranging from 5-20mcg/day	Insulin n=924 Participants insulin at a dose selected by the HCP and patient
Changes in HbA1c From Baseline to Month 24	-1.03 percentage of total hemoglobin Standard Deviation 1.48	-1.71 percentage of total hemoglobin Standard Deviation 1.82

SECONDARY outcome

Timeframe: Month 24

Population: Patients were assigned to the exenatide BID or insulin cohort based on their initial injectable treatment started at baseline, and analyses were conducted irrespective of later treatment changes. All patients who provided consent to release information and who fulfilled study entry criteria were included in this analysis population.

Percentage of Patients Achieving HbA1c Concentration \<7.0% at Month 24. Only patients with baseline HbA1c \>= 7.0 % were included in this analysis

Outcome measures

Outcome measures
Measure	Exenatide BID n=959 Participants daily dose ranging from 5-20mcg/day	Insulin n=1170 Participants insulin at a dose selected by the HCP and patient
Percentage of Patients Achieving HbA1c Concentration <7.0% at Month 24	26.9 percentage of patients	28.5 percentage of patients

SECONDARY outcome

Timeframe: Month 24

Population: Patients were assigned to the exenatide BID or insulin cohort based on their initial injectable treatment started at baseline, and analyses were conducted irrespective of later treatment changes. All patients who provided consent to release information and who fulfilled study entry criteria were included in this analysis population.

Percentage of Patients Achieving HbA1c Concentration \<6.5% at Month 24. Note: Only patients with baseline HbA1c \>=6.5% were included in this analysis.

Outcome measures

Outcome measures
Measure	Exenatide BID n=1019 Participants daily dose ranging from 5-20mcg/day	Insulin n=1208 Participants insulin at a dose selected by the HCP and patient
Percentage of Patients Achieving HbA1c Concentration <6.5% at Month 24	12.5 percentage of patients	10.7 percentage of patients

SECONDARY outcome

Timeframe: Baseline, Month 24

Population: Patients were assigned to the exenatide BID or insulin cohort based on their initial injectable treatment started at baseline, and analyses were conducted irrespective of later treatment changes. All patients who provided consent to release information and who fulfilled study entry criteria were included in this analysis population.

Changes in Weight From Baseline to Month 24