Trial Outcomes & Findings for Exenatide Versus Glimepiride in Patients With Type 2 Diabetes (NCT NCT00359762)
NCT ID: NCT00359762
Last Updated: 2015-09-15
Results Overview
Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
1029 participants
Primary outcome timeframe
Baseline to end of Period II (up to 4.5 years)
Results posted on
2015-09-15
Participant Flow
Patients meeting defined failure of HbA1c control (primary endpoint) in Study Period II were eligible for entry to Study Period III
Participant milestones
| Measure |
Period II, Glim + Met
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Period III, Exen + Met + Glim - Randomized
Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
|
Period III, Exen + Met + Pio or Rosi - Randomized
Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
|
Period III, Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
Period II, Exen + Met
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
|---|---|---|---|---|---|
|
Period II
STARTED
|
514
|
0
|
0
|
0
|
515
|
|
Period II
Intent to Treat (ITT) Safety Population
|
508
|
0
|
0
|
0
|
511
|
|
Period II
ITT Efficacy Population
|
487
|
0
|
0
|
0
|
490
|
|
Period II
Met Primary Endpoint
|
262
|
0
|
0
|
0
|
203
|
|
Period II
Without Treatment Failure
|
124
|
0
|
0
|
0
|
138
|
|
Period II
COMPLETED
|
386
|
0
|
0
|
0
|
341
|
|
Period II
NOT COMPLETED
|
128
|
0
|
0
|
0
|
174
|
|
Period III
STARTED
|
0
|
77
|
77
|
166
|
0
|
|
Period III
Extension ITT Safety Population
|
0
|
74
|
76
|
166
|
0
|
|
Period III
Extension ITT Efficacy Population
|
0
|
73
|
75
|
164
|
0
|
|
Period III
COMPLETED
|
0
|
48
|
47
|
101
|
0
|
|
Period III
NOT COMPLETED
|
0
|
29
|
30
|
65
|
0
|
|
Period I
STARTED
|
0
|
0
|
0
|
0
|
0
|
|
Period I
COMPLETED
|
0
|
0
|
0
|
0
|
0
|
|
Period I
NOT COMPLETED
|
0
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Period II, Glim + Met
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Period III, Exen + Met + Glim - Randomized
Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
|
Period III, Exen + Met + Pio or Rosi - Randomized
Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
|
Period III, Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
Period II, Exen + Met
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
|---|---|---|---|---|---|
|
Period II
Adverse Event
|
17
|
0
|
0
|
0
|
49
|
|
Period II
Protocol Violation
|
18
|
0
|
0
|
0
|
11
|
|
Period II
Physician Decision
|
17
|
0
|
0
|
0
|
23
|
|
Period II
Death
|
2
|
0
|
0
|
0
|
4
|
|
Period II
Lack of Efficacy
|
11
|
0
|
0
|
0
|
8
|
|
Period II
Lost to follow up
|
5
|
0
|
0
|
0
|
5
|
|
Period II
Entry Criteria Not Met
|
8
|
0
|
0
|
0
|
4
|
|
Period II
Subject Decision
|
50
|
0
|
0
|
0
|
70
|
|
Period III
Protocol Violation
|
0
|
5
|
3
|
8
|
0
|
|
Period III
Adverse Event
|
0
|
3
|
4
|
10
|
0
|
|
Period III
Physician Decision
|
0
|
5
|
9
|
15
|
0
|
|
Period III
Lack of Efficacy
|
0
|
7
|
5
|
9
|
0
|
|
Period III
Lost to follow up
|
0
|
1
|
1
|
2
|
0
|
|
Period III
Entry Criteria Not Met
|
0
|
1
|
0
|
1
|
0
|
|
Period III
Subject Decision
|
0
|
7
|
8
|
20
|
0
|
Baseline Characteristics
Exenatide Versus Glimepiride in Patients With Type 2 Diabetes
Baseline characteristics by cohort
| Measure |
Exen + Met
n=490 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=487 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Total
n=977 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
388 Participants
n=5 Participants
|
389 Participants
n=7 Participants
|
777 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
102 Participants
n=5 Participants
|
98 Participants
n=7 Participants
|
200 Participants
n=5 Participants
|
|
Age, Continuous
|
56.1 years
STANDARD_DEVIATION 10.03 • n=5 Participants
|
56.8 years
STANDARD_DEVIATION 9.14 • n=7 Participants
|
56.4 years
STANDARD_DEVIATION 9.60 • n=5 Participants
|
|
Sex: Female, Male
Female
|
218 Participants
n=5 Participants
|
235 Participants
n=7 Participants
|
453 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
272 Participants
n=5 Participants
|
252 Participants
n=7 Participants
|
524 Participants
n=5 Participants
|
|
Glycosylated hemoglobin (HbA1c)
|
7.4 percentage of total hemoglobin
STANDARD_DEVIATION 0.69 • n=5 Participants
|
7.4 percentage of total hemoglobin
STANDARD_DEVIATION 0.71 • n=7 Participants
|
7.4 percentage of total hemoglobin
STANDARD_DEVIATION 0.70 • n=5 Participants
|
|
Weight
|
92.8 kg
STANDARD_DEVIATION 16.70 • n=5 Participants
|
91.1 kg
STANDARD_DEVIATION 14.78 • n=7 Participants
|
92.0 kg
STANDARD_DEVIATION 15.78 • n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to end of Period II (up to 4.5 years)Population: ITT Efficacy Population: Enrolled patients with a baseline and at least one post-baseline measurement of HbA1c in Study Period II (including only Study Period II); patients analyzed according to treatment as randomized.
Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.
Outcome measures
| Measure |
Exen + Met
n=490 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=487 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Number of Patients With Treatment Failure
Number of patients with treatment failure
|
203 number of patients
|
262 number of patients
|
—
|
|
Number of Patients With Treatment Failure
Number of patients censored
|
287 number of patients
|
225 number of patients
|
—
|
PRIMARY outcome
Timeframe: Baseline to end of Period II (up to 4.5 years)Population: ITT Efficacy Population.
Treatment failure is defined as one of the following:1. HbA1c exceeding 9% at any visit after the initial 3 months of treatment (i.e., earliest at Month 6), on the maximally tolerated dose of antidiabetic agents. 2. HbA1c exceeding 7% at 2 consecutive visits 3 months apart, after the initial 6 months of treatment (i.e., earliest at Month 9), on the maximally tolerated dose of antidiabetic agents.
Outcome measures
| Measure |
Exen + Met
n=490 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=487 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Time to Treatment Failure
|
180.0 week
Interval 140.9 to
Since the last observed time point, beyond which all are missing, is still within the 95% confidence interval for the median survival time, the upper bound should be no less than the last observed time point, and is unknown due to censoring.
|
142.1 week
Interval 118.6 to 161.1
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Efficacy Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
HOMA-B at Year 3. HOMA-B is an index of beta-cell function and was calculated as: HOMA-B = (20 x fasting insulin (measured in pmol/L))/((fasting glucose (measured in mmol/L) - 3.5) x 7.175).
Outcome measures
| Measure |
Exen + Met
n=148 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=166 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Homeostasis Model Assessment of Beta-cell Function (HOMA-B) at Year 3
|
66.86 ratio
Standard Error 4.045
|
68.52 ratio
Standard Error 3.813
|
—
|
SECONDARY outcome
Timeframe: Baseline, end of Period II (up to 4.5 years)Population: ITT Efficacy Population. Missing data at endpoint was imputed using last observation carried forward (LOCF) approach.
Change in HOMA-B from baseline to endpoint.
Outcome measures
| Measure |
Exen + Met
n=326 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=329 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in HOMA-B From Baseline to Endpoint
|
5.56 ratio
Standard Error 6.147
|
19.92 ratio
Standard Error 6.340
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Efficacy Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio at Year 3.
Outcome measures
| Measure |
Exen + Met
n=152 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=170 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Fasting Proinsulin/Insulin Ratio at Year 3
|
0.22 ratio
Standard Error 0.023
|
0.23 ratio
Standard Error 0.022
|
—
|
SECONDARY outcome
Timeframe: Baseline, end of Period II (up to 4.5 years)Population: ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.
Change in fasting proinsulin (measured in pmol/L)/insulin (measured in pmol/L) ratio from baseline to endpoint.
Outcome measures
| Measure |
Exen + Met
n=326 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=331 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in Fasting Proinsulin/Insulin Ratio From Baseline to Endpoint.
|
0.03 ratio
Standard Error 0.014
|
0.05 ratio
Standard Error 0.015
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Efficacy Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
DI30/DG30 at Year 3. DI30/DG30 ratio was calculated as (30 minute post prandial insulin - fasting insulin) (measured in pmol/L)/(30 minute post prandial glucose - fasting glucose) (measured in mmol/L).
Outcome measures
| Measure |
Exen + Met
n=130 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=156 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Ratio of the 30 Minute Increment in Plasma Insulin Concentration and the 30 Minute Increment in Plasma Glucose During the Oral Glucose Tolerance Test (DI30/DG30 Ratio) at Year 3
|
25.81 ratio
Standard Error 3.323
|
26.38 ratio
Standard Error 3.032
|
—
|
SECONDARY outcome
Timeframe: Baseline, end of Period II (up to 4.5 years)Population: ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.
Change in DI30/DG30 ratio from baseline to endpoint.
Outcome measures
| Measure |
Exen + Met
n=302 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=311 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in DI30/DG30 Ratio From Baseline to Endpoint
|
12.10 ratio
Standard Error 4.115
|
0.91 ratio
Standard Error 4.299
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Efficacy Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Disposition Index at Year 3. Disposition index was calculated as (DI30/DG30 ratio)/(HOMA index for insulin resistance (HOMA-IR)); where HOMA-IR=(fasting insulin (measured in pmol/L) x fasting glucose (measured in mmol/L))/(22.5 x 7.175).
Outcome measures
| Measure |
Exen + Met
n=130 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=156 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Disposition Index at Year 3
|
12.56 ratio
Standard Error 1.179
|
7.89 ratio
Standard Error 1.078
|
—
|
SECONDARY outcome
Timeframe: Baseline, end of Period II (up to 4.5 years)Population: ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.
Change in disposition index from baseline to endpoint.
Outcome measures
| Measure |
Exen + Met
n=302 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=311 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in Disposition Index From Baseline to Endpoint
|
9.15 ratio
Standard Error 1.764
|
1.82 ratio
Standard Error 1.849
|
—
|
SECONDARY outcome
Timeframe: Baseline, Year 3 in Period IIPopulation: ITT Efficacy Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Change in HbA1c from baseline to Year 3.
Outcome measures
| Measure |
Exen + Met
n=182 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=197 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in HbA1c From Baseline to Year 3
|
-0.30 percentage of total hemoglobin
Standard Error 0.051
|
-0.12 percentage of total hemoglobin
Standard Error 0.049
|
—
|
SECONDARY outcome
Timeframe: Baseline, end of Period II (up to 4.5 years)Population: ITT Efficacy Population.
Change in HbA1c from baseline to endpoint. Endpoint for HbA1c was defined as the HbA1c measured at the treatment failure for patients reaching primary endpoint and was the last observation in study period II for other patients (either followed until the end of the study period II or discontinuing the study).
Outcome measures
| Measure |
Exen + Met
n=488 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=485 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in HbA1c From Baseline to Endpoint
|
-0.36 percentage of total hemoglobin
Standard Error 0.035
|
-0.21 percentage of total hemoglobin
Standard Error 0.035
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Efficacy Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Fasting plasma glucose at Year 3.
Outcome measures
| Measure |
Exen + Met
n=149 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=166 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Fasting Plasma Glucose at Year 3
|
7.27 mmol/L
Standard Error 0.127
|
7.96 mmol/L
Standard Error 0.120
|
—
|
SECONDARY outcome
Timeframe: Baseline, end of Period II (up to 4.5 years)Population: ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.
Change in fasting plasma glucose from baseline to endpoint.
Outcome measures
| Measure |
Exen + Met
n=327 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=329 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in Fasting Plasma Glucose From Baseline to Endpoint
|
-0.87 mmol/L
Standard Error 0.155
|
-0.41 mmol/L
Standard Error 0.161
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Efficacy Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Postprandial (2 hours) plasma glucose at Year 3.
Outcome measures
| Measure |
Exen + Met
n=138 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=160 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Postprandial (2 Hours) Plasma Glucose at Year 3
|
12.65 mmol/L
Standard Error 0.311
|
15.45 mmol/L
Standard Error 0.289
|
—
|
SECONDARY outcome
Timeframe: Baseline, end of Period II (up to 4.5 years)Population: ITT Efficacy Population. Missing data at endpoint was imputed using LOCF approach.
Change from baseline in postprandial (2 hours) plasma glucose to endpoint.
Outcome measures
| Measure |
Exen + Met
n=310 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=320 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in Postprandial (2 Hours) Plasma Glucose From Baseline to Endpoint
|
-2.72 mmol/L
Standard Error 0.275
|
-0.53 mmol/L
Standard Error 0.286
|
—
|
SECONDARY outcome
Timeframe: Baseline, Year 3 in Period IIPopulation: ITT Safety Population: Enrolled patients receiving at least one dose of study medication in Study Period II with patients analyzed according to treatment actually received. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Change in Body weight from baseline to Year 3.
Outcome measures
| Measure |
Exen + Met
n=185 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=201 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in Body Weight From Baseline to Year 3
|
-3.92 kg
Standard Error 0.335
|
1.47 kg
Standard Error 0.319
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Systolic Blood pressure at Year 3.
Outcome measures
| Measure |
Exen + Met
n=183 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=203 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Systolic Blood Pressure at Year 3
|
130.58 mmHg
Standard Error 0.891
|
135.78 mmHg
Standard Error 0.845
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Diastolic Blood pressure at Year 3.
Outcome measures
| Measure |
Exen + Met
n=183 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=203 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Diastolic Blood Pressure at Year 3
|
77.45 mmHg
Standard Error 0.544
|
79.16 mmHg
Standard Error 0.517
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Heart rate at Year 3.
Outcome measures
| Measure |
Exen + Met
n=181 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=199 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Heart Rate at Year 3
|
73.51 beats per minute
Standard Error 0.583
|
74.23 beats per minute
Standard Error 0.555
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Triglycerides at Year 3.
Outcome measures
| Measure |
Exen + Met
n=178 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=193 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Triglycerides at Year 3
|
1.69 mmol/L
Standard Error 0.065
|
1.95 mmol/L
Standard Error 0.062
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
Total Cholesterol at Year 3.
Outcome measures
| Measure |
Exen + Met
n=178 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=193 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Total Cholesterol at Year 3
|
4.77 mmol/L
Standard Error 0.057
|
4.75 mmol/L
Standard Error 0.054
|
—
|
SECONDARY outcome
Timeframe: Year 3 in Period IIPopulation: ITT Safety Population. The analysis included only time points up to that week where at least 25% of the originally enrolled population was still in the study. Missing data at Year 3 was not imputed.
HDL Cholesterol at Year 3.
Outcome measures
| Measure |
Exen + Met
n=178 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=195 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
High-density Lipoprotein (HDL) Cholesterol at Year 3
|
1.31 mmol/L
Standard Error 0.013
|
1.25 mmol/L
Standard Error 0.013
|
—
|
SECONDARY outcome
Timeframe: Baseline to end of Period II (up to 4.5 years)Population: ITT Safety Population.
All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration \<=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration \<=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.
Outcome measures
| Measure |
Exen + Met
n=511 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=508 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Hypoglycemia Rate Per Year
|
1.52 events per subject-year
Standard Error 0.142
|
5.32 events per subject-year
Standard Error 0.473
|
—
|
SECONDARY outcome
Timeframe: Baseline in Period III, Year 2 in Period IIIPopulation: Extension ITT Efficacy Population: Extension enrolled patients with at least one post-baseline measurement of HbA1c in Study Period III. The analysis included patients randomized at entry in study period III. Missing data at Year 2 was not imputed.
Change in HbA1c from baseline to Year 2.
Outcome measures
| Measure |
Exen + Met
n=44 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=42 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in HbA1c From Baseline to Year 2 for Patients Randomized at Entry in Period III
|
-0.19 percentage of total hemoglobin
Standard Error 0.099
|
-0.47 percentage of total hemoglobin
Standard Error 0.100
|
—
|
SECONDARY outcome
Timeframe: Baseline in Period III, Year 2 in Period IIIPopulation: Extension ITT Efficacy population. The analysis included patients not randomized at entry in study period III. Missing data at Year 2 was not imputed.
Change in HbA1c from baseline to Year 2.
Outcome measures
| Measure |
Exen + Met
n=89 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Change in HbA1c From Baseline to Year 2 for Patients Not Randomized at Entry in Period III
|
-0.47 percentage of total hemoglobin
Standard Deviation 0.984
|
—
|
—
|
SECONDARY outcome
Timeframe: Start of Period III to end of studyPopulation: Extension ITT Safety Population: Extension enrolled patients receiving at least one dose of study medication in Study Period III.
All hypoglycemia episodes were taken into account. Severe hypoglycemia: event requiring assistance of another person to administer carbohydrate, glucagons, or other resuscitative actions; Documented symptomatic hypoglycemia: event with typical symptoms accompanied by a measured plasma glucose concentration \<=70 mg/dL; Asymptomatic hypoglycemia: event not accompanied by typical symptoms but with a measured plasma glucose concentration \<=70 mg/dL; Probable symptomatic hypoglycemia: event with symptoms not accompanied by a plasma glucose determination.
Outcome measures
| Measure |
Exen + Met
n=74 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
Glim + Met
n=76 Participants
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Glim + Met + Exen - Not Randomized
n=166 Participants
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
|---|---|---|---|
|
Hypoglycemia Rate Per Year in Period III
|
2.78 events per subject-year
Standard Deviation 5.456
|
0.60 events per subject-year
Standard Deviation 1.674
|
4.62 events per subject-year
Standard Deviation 10.411
|
Adverse Events
Period II, Glim + Met
Serious events: 68 serious events
Other events: 248 other events
Deaths: 0 deaths
Period III, Exen + Met + Glim - Randomized
Serious events: 7 serious events
Other events: 39 other events
Deaths: 0 deaths
Period III, Exen + Met + Pio or Rosi - Randomized
Serious events: 13 serious events
Other events: 39 other events
Deaths: 0 deaths
Period III, Glim + Met + Exen - Not Randomized
Serious events: 19 serious events
Other events: 91 other events
Deaths: 0 deaths
Period II, Exen + Met
Serious events: 73 serious events
Other events: 311 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Period II, Glim + Met
n=508 participants at risk
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Period III, Exen + Met + Glim - Randomized
n=74 participants at risk
Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
|
Period III, Exen + Met + Pio or Rosi - Randomized
n=76 participants at risk
Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
|
Period III, Glim + Met + Exen - Not Randomized
n=166 participants at risk
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
Period II, Exen + Met
n=511 participants at risk
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
|---|---|---|---|---|---|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.20%
1/508
|
0.00%
0/74
|
1.3%
1/76
|
0.60%
1/166
|
0.59%
3/511
|
|
Injury, poisoning and procedural complications
Fall
|
0.39%
2/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.59%
3/511
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.59%
3/511
|
|
Cardiac disorders
Atrial fibrillation
|
0.39%
2/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.39%
2/511
|
|
Infections and infestations
Erysipelas
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.79%
4/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Renal and urinary disorders
Renal colic
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Respiratory, thoracic and mediastinal disorders
Sleep apnoea syndrome
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Nervous system disorders
Syncope
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Cardiac disorders
Tachyarrhythmia
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.39%
2/511
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
Abscess
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
Abscess limb
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Cardiac disorders
Acute coronary syndrome
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.20%
1/511
|
|
Blood and lymphatic system disorders
Anaemia
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Gastrointestinal disorders
Anal fissure
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Cardiac disorders
Atrial flutter
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Brain contusion
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Respiratory, thoracic and mediastinal disorders
Bullous lung disease
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Nervous system disorders
Carotid arteriosclerosis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
Cellulitis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Musculoskeletal and connective tissue disorders
Cervical spinal stenosis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
General disorders
Chest pain
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Hepatobiliary disorders
Cholecystitis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.00%
0/508
|
1.4%
1/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colon cancer
|
0.39%
2/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.20%
1/511
|
|
Gastrointestinal disorders
Colonic polyp
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Colorectal cancer
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Gastrointestinal disorders
Constipation
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Contusion
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Renal and urinary disorders
Cystitis haemorrhagic
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Vascular disorders
Deep vein thrombosis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Nervous system disorders
Encephalitis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Gastrointestinal disorders
Faecaloma
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gallbladder cancer
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
Gastroenteritis norovirus
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Glioblastoma
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
HIV infection
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Congenital, familial and genetic disorders
Haemophilia A with anti factor VIII
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
Helicobacter gastritis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
Influenza
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Injury
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc degeneration
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Nervous system disorders
Ischaemic stroke
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Limb crushing injury
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung squamous cell carcinoma stage unspecified
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Cardiac disorders
Myocardial infarction
|
0.39%
2/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Cardiac disorders
Palpitations
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Musculoskeletal and connective tissue disorders
Periarthritis
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.60%
1/166
|
0.20%
1/511
|
|
Infections and infestations
Pneumonia
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Pubis fracture
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.39%
2/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Nervous system disorders
Radiculopathy
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal cancer
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Renal and urinary disorders
Renal failure acute
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Nervous system disorders
Sciatica
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
Sinusitis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Sternal fracture
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Subdural haemorrhage
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
General disorders
Sudden cardiac death
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Injury, poisoning and procedural complications
Tendon rupture
|
0.59%
3/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Reproductive system and breast disorders
Uterine cervical erosion
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Infections and infestations
Viral labyrinthitis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.20%
1/511
|
|
Gastrointestinal disorders
Abdominal adhesions
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Gastrointestinal disorders
Abdominal hernia
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Accident
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Gastrointestinal disorders
Acute abdomen
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Cardiac disorders
Acute myocardial infarction
|
0.39%
2/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Anal abscess
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Cardiac disorders
Angina unstable
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
1.2%
2/166
|
0.00%
0/511
|
|
Eye disorders
Angle closure glaucoma
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Appendicitis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.39%
2/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer
|
0.39%
2/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder neoplasm
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer metastatic
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Bronchitis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Renal and urinary disorders
Calculus ureteric
|
0.00%
0/508
|
1.4%
1/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Cardiac disorders
Cardiac disorder
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Nervous system disorders
Carpal tunnel syndrome
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Chondropathy
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Clavicle fracture
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Cardiac disorders
Coronary artery disease
|
0.59%
3/508
|
1.4%
1/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Psychiatric disorders
Depression
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Congenital, familial and genetic disorders
Dermoid cyst
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Gastrointestinal disorders
Diverticulum intestinal
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Gastrointestinal disorders
Dyspepsia
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Endometrial cancer
|
0.00%
0/508
|
1.4%
1/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Reproductive system and breast disorders
Endometrial hyperplasia
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Reproductive system and breast disorders
Endometrial hypertrophy
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Fibula fracture
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Foot deformity
|
0.20%
1/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Foot fracture
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Gastric neoplasm
|
0.00%
0/508
|
1.4%
1/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Gastrointestinal disorders
Gastritis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Infections and infestations
Gastroenteritis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Gastrointestinal disorders
Gastrointestinal inflammation
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Endocrine disorders
Goitre
|
0.59%
3/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Gastrointestinal disorders
Haemorrhoids
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Vascular disorders
Hypertension
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
0.00%
0/508
|
1.4%
1/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
0.00%
0/508
|
1.4%
1/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Infected epidermal cyst
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Intervertebral discitis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Joint effusion
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Knee deformity
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Localised infection
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Eye disorders
Macular oedema
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Meniscus lesion
|
0.79%
4/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Psychiatric disorders
Mental disorder
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to bone
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastases to liver
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Reproductive system and breast disorders
Metrorrhagia
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Psychiatric disorders
Mood altered
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Cardiac disorders
Myocardial ischaemia
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Nervous system disorders
Nervous system disorder
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Renal and urinary disorders
Nocturia
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Metabolism and nutrition disorders
Obesity
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Musculoskeletal and connective tissue disorders
Osteitis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Osteomyelitis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/508
|
0.00%
0/74
|
0.00%
0/76
|
0.60%
1/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Pelvic fracture
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Cardiac disorders
Pericarditis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Post procedural haematoma
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Postoperative wound infection
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectosigmoid cancer
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal neoplasm
|
0.00%
0/508
|
0.00%
0/74
|
1.3%
1/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer stage unspecified
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Sports injury
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Staphylococcal sepsis
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Infections and infestations
Subcutaneous abscess
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Nervous system disorders
Transient global amnesia
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Injury, poisoning and procedural complications
Ureteric injury
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Renal and urinary disorders
Urinary bladder polyp
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Renal and urinary disorders
Urinary tract inflammation
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine cancer
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
|
Reproductive system and breast disorders
Uterine polyp
|
0.20%
1/508
|
0.00%
0/74
|
0.00%
0/76
|
0.00%
0/166
|
0.00%
0/511
|
Other adverse events
| Measure |
Period II, Glim + Met
n=508 participants at risk
Glimepiride one 1 mg tablet daily with subsequent titration every 4 weeks to maximally-tolerated dose for the remainder of Period II and daily oral Metformin
|
Period III, Exen + Met + Glim - Randomized
n=74 participants at risk
Glimepiride once daily, started at 1 mg dose and titrated up to maintenance doses, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
|
Period III, Exen + Met + Pio or Rosi - Randomized
n=76 participants at risk
Oral Rosiglitazone or Pioglitazone once or twice daily, started 15 mg per day, was added to Exenatide 10 mcg twice daily subcutaneously injected and daily oral Metformin in Period III
|
Period III, Glim + Met + Exen - Not Randomized
n=166 participants at risk
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for the first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period III) was added to oral Glimepiride once daily and daily oral Metformin in Period III
|
Period II, Exen + Met
n=511 participants at risk
Exenatide 10 mcg twice daily subcutaneously injected (5 mcg exenatide per dose for first 4 weeks followed by 10 mcg exenatide per dose for the remainder of period II) and daily oral Metformin
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
Nausea
|
2.2%
11/508
|
13.5%
10/74
|
11.8%
9/76
|
22.9%
38/166
|
28.8%
147/511
|
|
Infections and infestations
Nasopharyngitis
|
18.3%
93/508
|
27.0%
20/74
|
19.7%
15/76
|
16.3%
27/166
|
18.8%
96/511
|
|
Gastrointestinal disorders
Diarrhoea
|
6.5%
33/508
|
9.5%
7/74
|
9.2%
7/76
|
7.8%
13/166
|
12.1%
62/511
|
|
Nervous system disorders
Headache
|
9.4%
48/508
|
14.9%
11/74
|
9.2%
7/76
|
6.0%
10/166
|
11.0%
56/511
|
|
Infections and infestations
Influenza
|
6.9%
35/508
|
9.5%
7/74
|
7.9%
6/76
|
4.8%
8/166
|
10.6%
54/511
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.6%
54/508
|
6.8%
5/74
|
11.8%
9/76
|
5.4%
9/166
|
10.2%
52/511
|
|
Gastrointestinal disorders
Vomiting
|
2.4%
12/508
|
5.4%
4/74
|
1.3%
1/76
|
7.8%
13/166
|
8.6%
44/511
|
|
Infections and infestations
Bronchitis
|
6.1%
31/508
|
2.7%
2/74
|
9.2%
7/76
|
3.0%
5/166
|
6.7%
34/511
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
8.1%
41/508
|
2.7%
2/74
|
2.6%
2/76
|
3.6%
6/166
|
4.1%
21/511
|
|
Gastrointestinal disorders
Dyspepsia
|
2.8%
14/508
|
5.4%
4/74
|
0.00%
0/76
|
8.4%
14/166
|
5.1%
26/511
|
|
Infections and infestations
Pharyngitis
|
4.1%
21/508
|
2.7%
2/74
|
2.6%
2/76
|
3.0%
5/166
|
5.1%
26/511
|
|
Gastrointestinal disorders
Abdominal pain upper
|
2.6%
13/508
|
8.1%
6/74
|
2.6%
2/76
|
3.6%
6/166
|
4.1%
21/511
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.9%
25/508
|
5.4%
4/74
|
5.3%
4/76
|
6.0%
10/166
|
3.5%
18/511
|
|
Infections and infestations
Gastroenteritis
|
2.6%
13/508
|
5.4%
4/74
|
3.9%
3/76
|
5.4%
9/166
|
3.5%
18/511
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
4.3%
22/508
|
4.1%
3/74
|
2.6%
2/76
|
6.0%
10/166
|
3.1%
16/511
|
|
Vascular disorders
Hypertension
|
4.7%
24/508
|
8.1%
6/74
|
3.9%
3/76
|
5.4%
9/166
|
2.9%
15/511
|
|
Infections and infestations
Cystitis
|
3.7%
19/508
|
6.8%
5/74
|
3.9%
3/76
|
2.4%
4/166
|
2.7%
14/511
|
|
Gastrointestinal disorders
Abdominal pain
|
2.0%
10/508
|
5.4%
4/74
|
1.3%
1/76
|
2.4%
4/166
|
2.2%
11/511
|
|
General disorders
Oedema peripheral
|
2.2%
11/508
|
0.00%
0/74
|
6.6%
5/76
|
1.2%
2/166
|
1.2%
6/511
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60