Trial Outcomes & Findings for A Study in Participants With Type I Diabetes Mellitus (NCT NCT01454284)
NCT ID: NCT01454284
Last Updated: 2018-04-17
Results Overview
HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, stratification factors (country, baseline low density lipoprotein cholesterol \[LDL-C\] \[\<100 milligrams/deciliter (mg/dL) (2.6 millimoles/liter \[mmol/L\]) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
COMPLETED
PHASE3
1114 participants
52 weeks
2018-04-17
Participant Flow
Participant milestones
| Measure |
LY2605541 + Insulin Lispro
Includes participants randomized to receive LY2605541 plus Insulin Lispro.
Participant-specific dose of LY2605541 was administered subcutaneously (SC) once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
Includes participants randomized to receive Insulin Glargine plus Insulin Lispro.
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
664
|
450
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
663
|
449
|
|
Overall Study
COMPLETED
|
548
|
377
|
|
Overall Study
NOT COMPLETED
|
116
|
73
|
Reasons for withdrawal
| Measure |
LY2605541 + Insulin Lispro
Includes participants randomized to receive LY2605541 plus Insulin Lispro.
Participant-specific dose of LY2605541 was administered subcutaneously (SC) once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
Includes participants randomized to receive Insulin Glargine plus Insulin Lispro.
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
20
|
7
|
|
Overall Study
Death
|
0
|
3
|
|
Overall Study
Lost to Follow-up
|
13
|
8
|
|
Overall Study
Protocol Violation
|
9
|
6
|
|
Overall Study
Withdrawal by Subject
|
58
|
36
|
|
Overall Study
Physician Decision
|
16
|
11
|
|
Overall Study
Sponsor Decision
|
0
|
2
|
Baseline Characteristics
A Study in Participants With Type I Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
LY2605541 + Insulin Lispro
n=664 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=450 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Total
n=1114 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
41.58 years
STANDARD_DEVIATION 13.50 • n=5 Participants
|
42.28 years
STANDARD_DEVIATION 13.16 • n=7 Participants
|
41.86 years
STANDARD_DEVIATION 13.36 • n=5 Participants
|
|
Sex: Female, Male
Female
|
267 Participants
n=5 Participants
|
169 Participants
n=7 Participants
|
436 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
397 Participants
n=5 Participants
|
281 Participants
n=7 Participants
|
678 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
23 Participants
n=5 Participants
|
18 Participants
n=7 Participants
|
41 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
477 Participants
n=5 Participants
|
315 Participants
n=7 Participants
|
792 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
164 Participants
n=5 Participants
|
117 Participants
n=7 Participants
|
281 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
6 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
15 Participants
n=5 Participants
|
14 Participants
n=7 Participants
|
29 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
625 Participants
n=5 Participants
|
426 Participants
n=7 Participants
|
1051 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
15 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
21 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
343 Participants
n=5 Participants
|
229 Participants
n=7 Participants
|
572 Participants
n=5 Participants
|
|
Region of Enrollment
Slovakia
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Greece
|
15 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Region of Enrollment
Spain
|
44 Participants
n=5 Participants
|
30 Participants
n=7 Participants
|
74 Participants
n=5 Participants
|
|
Region of Enrollment
Ireland
|
2 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
Region of Enrollment
Lithuania
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
Israel
|
13 Participants
n=5 Participants
|
9 Participants
n=7 Participants
|
22 Participants
n=5 Participants
|
|
Region of Enrollment
United Kingdom
|
38 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
63 Participants
n=5 Participants
|
|
Region of Enrollment
France
|
12 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
19 Participants
n=5 Participants
|
|
Region of Enrollment
Canada
|
33 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
52 Participants
n=5 Participants
|
|
Region of Enrollment
Belgium
|
20 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
36 Participants
n=5 Participants
|
|
Region of Enrollment
Brazil
|
19 Participants
n=5 Participants
|
11 Participants
n=7 Participants
|
30 Participants
n=5 Participants
|
|
Region of Enrollment
Poland
|
51 Participants
n=5 Participants
|
33 Participants
n=7 Participants
|
84 Participants
n=5 Participants
|
|
Region of Enrollment
Croatia
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Region of Enrollment
Denmark
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
Australia
|
22 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
39 Participants
n=5 Participants
|
|
Region of Enrollment
South Africa
|
16 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
24 Participants
n=5 Participants
|
|
Region of Enrollment
Netherlands
|
2 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Region of Enrollment
New Zealand
|
9 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
14 Participants
n=5 Participants
|
|
Region of Enrollment
Sweden
|
13 Participants
n=5 Participants
|
13 Participants
n=7 Participants
|
26 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.
HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for treatment, stratification factors (country, baseline low density lipoprotein cholesterol \[LDL-C\] \[\<100 milligrams/deciliter (mg/dL) (2.6 millimoles/liter \[mmol/L\]) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=648 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=444 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Hemoglobin A1c (HbA1c)
|
7.38 percentage of HbA1c
Standard Error 0.03
|
7.61 percentage of HbA1c
Standard Error 0.04
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.
HbA1c is a test that measures a participant's average blood glucose level over the past 2 to 3 months. LS means were calculated using MMRM adjusting for treatment, stratification factors (country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=648 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=444 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Hemoglobin A1c (HbA1c)
|
7.09 percentage of HbA1c
Standard Error 0.03
|
7.42 percentage of HbA1c
Standard Error 0.03
|
SECONDARY outcome
Timeframe: Baseline, 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.
HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. LS means were calculated using MMRM adjusting for treatment, stratification factors (country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=648 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=444 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Change From Baseline to 52 Weeks in HbA1c
|
-0.46 percentage of HbA1c
Standard Error 0.03
|
-0.24 percentage of HbA1c
Standard Error 0.04
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks, Baseline through 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.
Hypoglycemic episodes are defined as events which are associated with reported signs and symptoms of hypoglycemia and/or documented blood glucose (BG) concentrations of ≤70 mg/dL (3.9 mmol/L). Group mean rates of total hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline total hypoglycemia rate, with log \[exposure in days/30\] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=662 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=449 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Total Hypoglycemia Events
Weeks 0-26
|
16.83 episodes/participant/30 days
Standard Error 0.36
|
14.66 episodes/participant/30 days
Standard Error 0.36
|
|
Total Hypoglycemia Events
Weeks 0-52
|
15.34 episodes/participant/30 days
Standard Error 0.32
|
13.88 episodes/participant/30 days
Standard Error 0.35
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks, Baseline through 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.
Hypoglycemic episodes are defined as events that are associated with the reported signs and symptoms of hypoglycemia and/or documented BG concentrations of ≤70 mg/dL (3.9 mmol/L). The percentage of participants was calculated by dividing the number of participants with hypoglycemic episodes by the total number of participants analyzed, multiplied by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=662 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=449 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Percentage of Participants With Total Hypoglycemic Events
Weeks 0-26
|
99.1 percentage of participants
|
99.3 percentage of participants
|
|
Percentage of Participants With Total Hypoglycemic Events
Weeks 0-52
|
99.2 percentage of participants
|
99.3 percentage of participants
|
SECONDARY outcome
Timeframe: up to 26 weeks, up to 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data. Missing endpoints were imputed with the last observation carried forward (LOCF) method, using only post-baseline data.
The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=648 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=444 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Percentage of Participants With HbA1c Equal to or Less Than 6.5% and Less Than 7.0%
HbA1c ≤6.5%, Week 26
|
29.6 percentage of participants
|
17.8 percentage of participants
|
|
Percentage of Participants With HbA1c Equal to or Less Than 6.5% and Less Than 7.0%
HbA1c ≤6.5%, Week 52
|
20.8 percentage of participants
|
15.1 percentage of participants
|
|
Percentage of Participants With HbA1c Equal to or Less Than 6.5% and Less Than 7.0%
HbA1c <7.0%, Week 26
|
45.1 percentage of participants
|
34.5 percentage of participants
|
|
Percentage of Participants With HbA1c Equal to or Less Than 6.5% and Less Than 7.0%
HbA1c <7.0%, Week 52
|
35.3 percentage of participants
|
26.1 percentage of participants
|
SECONDARY outcome
Timeframe: up to 26 weeks, up to 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data. Missing endpoints were imputed with the LOCF method, using only post-baseline data.
Hypoglycemic episodes are defined as events associated with reported signs and symptoms of hypoglycemia and/or a documented blood glucose concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with HbA1c \<7.0% without nocturnal hypoglycemia by the total number of participants analyzed, multiplied by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=648 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=444 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Percentage of Participants With HbA1c Less Than 7.0% and Without Nocturnal Hypoglycemia
Week 26
|
7.1 percentage of participants
|
1.8 percentage of participants
|
|
Percentage of Participants With HbA1c Less Than 7.0% and Without Nocturnal Hypoglycemia
Week 52
|
4.3 percentage of participants
|
1.1 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks, Baseline through 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.
Hypoglycemic episodes are defined as events that are associated with reported signs and symptoms of hypoglycemia and/or a documented BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. Group mean rates of nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline nocturnal hypoglycemia rate, with log \[exposure in days/30\] as an offset variable). Group mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=662 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=449 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Nocturnal Hypoglycemia Rates
Weeks 0-26
|
1.37 events/participant/30 days
Standard Error 0.07
|
2.70 events/participant/30 days
Standard Error 0.12
|
|
Nocturnal Hypoglycemia Rates
Weeks 0-52
|
1.31 events/participant/30 days
Standard Error 0.06
|
2.46 events/participant/30 days
Standard Error 0.10
|
SECONDARY outcome
Timeframe: Baseline through 26 weeks, Baseline through 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable data at both baseline and post-baseline.
Hypoglycemic episodes are defined as events associated with the reported signs and symptoms of hypoglycemia and/or a BG concentration of ≤70 mg/dL (3.9 mmol/L). A nocturnal hypoglycemic event occurred between bedtime and waking and between the time points of 10:00 PM and 10:00 AM. The percentage of participants was calculated by dividing the number of participants with nocturnal hypoglycemic episodes by the total number of participants analyzed, multiplied by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=662 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=449 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Percentage of Participants With Nocturnal Hypoglycemic Events
Weeks 0-26
|
81.7 percentage of participants
|
94.7 percentage of participants
|
|
Percentage of Participants With Nocturnal Hypoglycemic Events
Weeks 0-52
|
87.5 percentage of participants
|
96.2 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 26 weeks, 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable body weight data at both baseline and post-baseline.
LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline body weight as fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=648 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=439 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Change in Body Weight
Week 26
|
-0.55 kilograms (kg)
Standard Error 0.14
|
0.78 kilograms (kg)
Standard Error 0.16
|
|
Change in Body Weight
Week 52
|
-0.61 kilograms (kg)
Standard Error 0.17
|
1.21 kilograms (kg)
Standard Error 0.20
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at both baseline and post-baseline.
9-point SMBG profiles were obtained over 2 days within the week prior to Weeks 0, 4, 12, 26, 39, and 52. SMBG measurements were taken at 9 time points: pre-morning meal, 2 hours post-morning meal, pre-midday meal, 2 hours post-midday meal, pre-evening meal, 2 hours post-evening meal, bedtime, at approximately 0300 hours, and the subsequent morning prior to the morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline BG values as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=615 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=416 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal, Week 26
|
153.85 mg/dL
Standard Error 2.67
|
148.91 mg/dL
Standard Error 3.17
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal, Week 52
|
156.18 mg/dL
Standard Error 2.75
|
155.25 mg/dL
Standard Error 3.30
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hour post-morning meal, Week 26
|
164.59 mg/dL
Standard Error 3.44
|
178.47 mg/dL
Standard Error 4.07
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hour post-morning meal, Week 52
|
171.94 mg/dL
Standard Error 3.43
|
183.35 mg/dL
Standard Error 4.10
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-midday meal, Week 26
|
136.70 mg/dL
Standard Error 2.70
|
152.87 mg/dL
Standard Error 3.22
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-midday meal, Week 52
|
145.22 mg/dL
Standard Error 2.87
|
158.50 mg/dL
Standard Error 3.42
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hour post-midday meal, Week 26
|
150.66 mg/dL
Standard Error 3.32
|
164.47 mg/dL
Standard Error 3.94
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hour post-midday meal, Week 52
|
156.92 mg/dL
Standard Error 3.73
|
172.61 mg/dL
Standard Error 4.42
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-evening meal, Week 26
|
155.38 mg/dL
Standard Error 3.13
|
176.50 mg/dL
Standard Error 3.73
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-evening meal, Week 52
|
153.30 mg/dL
Standard Error 3.21
|
170.83 mg/dL
Standard Error 3.79
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hour post-evening meal, Week 26
|
160.50 mg/dL
Standard Error 3.85
|
181.18 mg/dL
Standard Error 4.54
|
|
9 Point Self-monitored Blood Glucose (SMBG)
2 hour post-evening meal, Week 52
|
169.61 mg/dL
Standard Error 4.19
|
184.19 mg/dL
Standard Error 4.99
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Bedtime, Week 26
|
163.90 mg/dL
Standard Error 3.24
|
180.97 mg/dL
Standard Error 3.84
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Bedtime, Week 52
|
168.04 mg/dL
Standard Error 3.58
|
187.09 mg/dL
Standard Error 4.30
|
|
9 Point Self-monitored Blood Glucose (SMBG)
0300 Hours, Week 26
|
169.64 mg/dL
Standard Error 3.69
|
163.09 mg/dL
Standard Error 4.39
|
|
9 Point Self-monitored Blood Glucose (SMBG)
0300 Hours, Week 52
|
168.72 mg/dL
Standard Error 3.94
|
174.11 mg/dL
Standard Error 4.72
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal next day, Week 26
|
150.04 mg/dL
Standard Error 2.76
|
145.77 mg/dL
Standard Error 3.23
|
|
9 Point Self-monitored Blood Glucose (SMBG)
Pre-morning meal next day, Week 52
|
151.22 mg/dL
Standard Error 2.70
|
149.56 mg/dL
Standard Error 3.20
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable FSG data at both baseline and post-baseline.
Fasting serum glucose (FSG) is measured in blood before the morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=646 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=443 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Fasting Serum Glucose (by Laboratory Measurement)
Week 26
|
139.76 mg/dL
Standard Error 2.75
|
155.23 mg/dL
Standard Error 3.25
|
|
Fasting Serum Glucose (by Laboratory Measurement)
Week 52
|
142.02 mg/dL
Standard Error 2.95
|
171.67 mg/dL
Standard Error 3.48
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable FBG data at both baseline and post-baseline.
Fasting blood glucose (FBG) was measured by SMBG pre-morning meal. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline FBG as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=643 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=441 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Fasting Blood Glucose (by Participant Self Monitored Blood Glucose Readings)
Week 26
|
154.84 mg/dL
Standard Error 1.96
|
151.46 mg/dL
Standard Error 2.31
|
|
Fasting Blood Glucose (by Participant Self Monitored Blood Glucose Readings)
Week 52
|
159.85 mg/dL
Standard Error 2.02
|
153.09 mg/dL
Standard Error 2.39
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable FBG data at both baseline and post-baseline.
FBG was measured by SMBG. Between-day glucose variability is measured by the standard deviation (SD) of FBG. LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline SD of FBG as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=639 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=437 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Intra-participant Variability of Fasting Blood Glucose (FBG)
Week 26
|
51.70 mg/dL
Standard Error 1.22
|
64.73 mg/dL
Standard Error 1.44
|
|
Intra-participant Variability of Fasting Blood Glucose (FBG)
Week 52
|
53.97 mg/dL
Standard Error 1.24
|
63.11 mg/dL
Standard Error 1.46
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at baseline and post-baseline.
Results of a 0300-hour to pre-morning meal (FBG) excursion are presented (only excursions within a single SMBG profile are included). LS means were calculated using MMRM adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], baseline prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment-by-visit interaction, and baseline excursion as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=498 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=332 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
0300 Hours Blood Glucose (BG) to Fasting BG Excursion
Week 26
|
-25.49 mg/dL
Standard Error 3.96
|
-16.44 mg/dL
Standard Error 4.72
|
|
0300 Hours Blood Glucose (BG) to Fasting BG Excursion
Week 52
|
-23.36 mg/dL
Standard Error 4.10
|
-29.01 mg/dL
Standard Error 4.87
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable lipid data at both baseline and post-baseline.
Concentrations of cholesterol, HDL-C, and LDL-C, and triglycerides are presented. LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L), except for the LDL-C outcome variable\], prior basal insulin therapy \[insulin glargine/detemir/other\]), visit, treatment, treatment-by-visit interaction, and baseline value of corresponding lipid outcome variable as the fixed effects and participant as a random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=650 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=446 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
Cholesterol, Week 26
|
185.51 mg/dL
Standard Error 1.09
|
179.30 mg/dL
Standard Error 1.29
|
|
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
Cholesterol, Week 52
|
184.66 mg/dL
Standard Error 1.13
|
178.13 mg/dL
Standard Error 1.34
|
|
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
HDL-C, Week 26
|
58.44 mg/dL
Standard Error 0.39
|
61.52 mg/dL
Standard Error 0.46
|
|
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
HDL-C, Week 52
|
58.13 mg/dL
Standard Error 0.39
|
59.52 mg/dL
Standard Error 0.46
|
|
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
LDL-C, Week 26
|
106.25 mg/dL
Standard Error 0.90
|
100.90 mg/dL
Standard Error 1.07
|
|
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
LDL-C, Week 52
|
105.80 mg/dL
Standard Error 0.96
|
101.20 mg/dL
Standard Error 1.14
|
|
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
Triglycerides, Week 26
|
105.26 mg/dL
Standard Error 2.30
|
85.11 mg/dL
Standard Error 2.73
|
|
Triglycerides, Low Density Lipoprotein Cholesterol (LDL-C), High Density Lipoprotein Cholesterol (HDL-C), and Total Cholesterol
Triglycerides, Week 52
|
104.84 mg/dL
Standard Error 2.17
|
88.12 mg/dL
Standard Error 2.57
|
SECONDARY outcome
Timeframe: 26 weeks, 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable anti-LY2605541 antibody data at baseline and post-baseline.
The percentage of participants with anti-LY2605541 treatment-emergent antibody response (TEAR) is summarized. TEAR is defined as change from baseline to post-baseline in the anti-LY2605541 antibody level either from undetectable to detectable, or from detectable to the value with at least 130% relative increase from baseline.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=556 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=399 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Percentage of Participants With Change in Anti-LY2605541 Antibodies
Week 26
|
30.2 percentage of participants
|
14.0 percentage of participants
|
|
Percentage of Participants With Change in Anti-LY2605541 Antibodies
Week 52
|
32.8 percentage of participants
|
10.2 percentage of participants
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable insulin dose data.
Basal insulin dose, meal-time insulin dose (short-acting bolus dose), and total insulin dose were calculated based on the dose during the last 7 days prior to the post-treatment visit or last 3 days prior to the randomization visit. LS means were calculated using a constrained Longitudinal Data Analysis (cLDA) model adjusting for indicator variables of each treatment group at each postbaseline visit and stratification variables (baseline HbA1c \[≤8.5% and\> 8.5%\], country, baseline LDL-C \[\<100 mg/dL (2.6 mmol/L) and ≥100 mg/dL (2.6 mmol/L)\], and baseline prior basal insulin therapy \[insulin glargine/detemir/ other\]) as fixed effects.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=551 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=392 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Basal, Meal Time, and Total Insulin Dose Per Body Weight
Total insulin, Week 26
|
0.75 units/weight/day
Standard Error 0.01
|
0.77 units/weight/day
Standard Error 0.01
|
|
Basal, Meal Time, and Total Insulin Dose Per Body Weight
Basal insulin, Week 26
|
0.46 units/weight/day
Standard Error 0.01
|
0.35 units/weight/day
Standard Error 0.01
|
|
Basal, Meal Time, and Total Insulin Dose Per Body Weight
Basal insulin, Week 52
|
0.47 units/weight/day
Standard Error 0.01
|
0.35 units/weight/day
Standard Error 0.01
|
|
Basal, Meal Time, and Total Insulin Dose Per Body Weight
Meal time insulin, Week 26
|
0.32 units/weight/day
Standard Error 0.01
|
0.44 units/weight/day
Standard Error 0.01
|
|
Basal, Meal Time, and Total Insulin Dose Per Body Weight
Meal time insulin, Week 52
|
0.33 units/weight/day
Standard Error 0.01
|
0.43 units/weight/day
Standard Error 0.01
|
|
Basal, Meal Time, and Total Insulin Dose Per Body Weight
Total insulin, Week 52
|
0.78 units/weight/day
Standard Error 0.01
|
0.77 units/weight/day
Standard Error 0.02
|
SECONDARY outcome
Timeframe: up to 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable ITSQ data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.
Insulin Treatment Satisfaction Questionnaire (ITSQ) is a validated measure containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Convenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, and Insulin Delivery Device. Data are transformed to a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an ANCOVA model adjusting for treatment, baseline HbA1c (≤8.5% and \>8.5%), country, and baseline prior basal insulin therapy (insulin glargine/detemir/other) as fixed effects and baseline ITSQ scores as a covariate.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=561 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=406 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Insulin Treatment Satisfaction Questionnaire
|
73.60 units on a scale
Standard Error 0.57
|
72.92 units on a scale
Standard Error 0.67
|
SECONDARY outcome
Timeframe: up to 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable EQ-5D-3L data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.
The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three-level scale of 1-3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores range from -0.11 to 1.0, where a score of 1.0 indicates perfect health. LS means were calculated using an ANCOVA adjusting for treatment, baseline HbA1c (≤8.5% and \>8.5%), country, baseline prior basal insulin therapy (insulin glargine/detemir/other), and baseline EQ-5D-3L score as covariates.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=566 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=406 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
European Quality of Life -5 Dimension (EQ-5D-3L)
|
0.91 units on a scale
Standard Error 0.00
|
0.92 units on a scale
Standard Error 0.01
|
SECONDARY outcome
Timeframe: 26 weeks and 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable LBSS data at both baseline and post-baseline.
Low Blood Sugar Survey (LBSS) (also referenced as Hypoglycemia Fear Survey - II \[HFS-II\]) is a questionnaire that measures 1) behaviors to avoid hypoglycemia and its negative consequences (15 items) and 2) worries about hypoglycemia and its negative consequences (18 items). Responses are made on a 5-point Likert-type scale where 0 = Never and 4 = Always. Total score is the sum of all items (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using MMRM adjusting for treatment, baseline HbA1c (≤8.5% and \>8.5%), country, baseline prior basal insulin therapy (insulin glargine/detemir/other), visit, treatment-by-visit interaction, and baseline LBSS score as the fixed effects and participant as the random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=657 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=447 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Adult Low Blood Sugar Survey
Week 26
|
29.48 units on a scale
Standard Error 0.55
|
29.12 units on a scale
Standard Error 0.65
|
|
Adult Low Blood Sugar Survey
Week 52
|
30.43 units on a scale
Standard Error 0.59
|
29.27 units on a scale
Standard Error 0.70
|
SECONDARY outcome
Timeframe: 52 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable RAPA data.
The RAPA questionnaire assesses the level and intensity of physical activity of adult participants. It contains 2 subscales: RAPA 1 (Aerobic) and RAPA 2 (Strength and Flexibility). RAPA 1 contains 7 questions regarding the participant's amount and intensity of physical activity, allowing each participant's aerobic activity level to be categorized as sedentary, underactive, light activity, regular underactive, or active. RAPA 2 contains 2 questions regarding participants' physical activities that increase strength and improve flexibility. Each participant's strength and flexibility activity level is then categorized as neither strength nor flexibility activity, either strength or flexibility activity (not both), both strength and flexibility activity. The percentage of participants in each RAPA 1/2 category is presented and was calculated by dividing the number of participants in each RAPA 1/2 category by the total number of participants analyzed, multiplied by 100.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=367 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=254 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Sedentary
|
1.1 percentage of participants
|
1.2 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Underactive
|
3.8 percentage of participants
|
4.8 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Light activity
|
13.7 percentage of participants
|
14.5 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Regular underactive
|
24.5 percentage of participants
|
28.5 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 1, Active
|
56.9 percentage of participants
|
51.0 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Neither strength/flexibility
|
39.0 percentage of participants
|
46.9 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Either strength/flexibility
|
28.9 percentage of participants
|
26.8 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA)
RAPA 2, Both strength/flexibility
|
32.2 percentage of participants
|
26.4 percentage of participants
|
Adverse Events
LY2605541 + Insulin Lispro
Insulin Glargine + Insulin Lispro
Serious adverse events
| Measure |
LY2605541 + Insulin Lispro
n=663 participants at risk
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=449 participants at risk
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Nervous system disorders
Transient global amnesia
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Nervous system disorders
Transient ischaemic attack
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Pregnancy, puerperium and perinatal conditions
Hyperemesis gravidarum
|
0.00%
0/267
|
0.59%
1/169 • Number of events 1
|
|
Pregnancy, puerperium and perinatal conditions
Pregnancy
|
0.37%
1/267 • Number of events 1
|
0.00%
0/169
|
|
Psychiatric disorders
Acute psychosis
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Blood and lymphatic system disorders
Autoimmune thrombocytopenia
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Cardiac disorders
Acute myocardial infarction
|
0.15%
1/663 • Number of events 1
|
0.45%
2/449 • Number of events 3
|
|
Cardiac disorders
Angina pectoris
|
0.00%
0/663
|
0.45%
2/449 • Number of events 2
|
|
Cardiac disorders
Angina unstable
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Cardiac disorders
Arteriosclerosis coronary artery
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Cardiac disorders
Cardiac failure
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Cardiac disorders
Coronary artery disease
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Cardiac disorders
Coronary artery occlusion
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Cardiac disorders
Myocardial infarction
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Gastrointestinal disorders
Colitis microscopic
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Gastrointestinal disorders
Constipation
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Gastrointestinal disorders
Enteritis
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Gastrointestinal disorders
Gastric ulcer
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Gastrointestinal disorders
Gastritis
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.15%
1/663 • Number of events 1
|
0.22%
1/449 • Number of events 1
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
General disorders
Pyrexia
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.15%
1/663 • Number of events 2
|
0.00%
0/449
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.15%
1/663 • Number of events 1
|
0.22%
1/449 • Number of events 1
|
|
Immune system disorders
Drug hypersensitivity
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Immune system disorders
Food allergy
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Infections and infestations
Abscess limb
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Infections and infestations
Abscess oral
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Infections and infestations
Appendicitis
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Infections and infestations
Cellulitis
|
0.30%
2/663 • Number of events 2
|
0.22%
1/449 • Number of events 1
|
|
Infections and infestations
Gastritis viral
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Infections and infestations
Gastroenteritis
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Infections and infestations
Lobar pneumonia
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Infections and infestations
Pneumonia
|
0.30%
2/663 • Number of events 2
|
0.00%
0/449
|
|
Infections and infestations
Pyelonephritis
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Infections and infestations
Sepsis
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Infections and infestations
Viraemia
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Injury, poisoning and procedural complications
Accident at home
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Eye injury
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Injury, poisoning and procedural complications
Gun shot wound
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Hand fracture
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Intentional overdose
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Radius fracture
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Rib fracture
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.15%
1/663 • Number of events 1
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Thermal burn
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.00%
0/663
|
0.45%
2/449 • Number of events 3
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Injury, poisoning and procedural complications
Wrist fracture
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Investigations
Hepatic enzyme increased
|
0.15%
1/663 • Number of events 2
|
0.00%
0/449
|
|
Investigations
Liver function test abnormal
|
0.00%
0/663
|
0.22%
1/449 • Number of events 2
|
|
Investigations
Weight decreased
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Metabolism and nutrition disorders
Diabetic ketoacidosis
|
0.45%
3/663 • Number of events 3
|
1.3%
6/449 • Number of events 7
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
0.15%
1/663 • Number of events 1
|
0.67%
3/449 • Number of events 4
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
10.7%
71/663 • Number of events 108
|
12.9%
58/449 • Number of events 95
|
|
Metabolism and nutrition disorders
Ketoacidosis
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Lumbar spinal stenosis
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Musculoskeletal and connective tissue disorders
Neuropathic arthropathy
|
0.15%
1/663 • Number of events 2
|
0.00%
0/449
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma gastric
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.15%
1/663 • Number of events 1
|
0.22%
1/449 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign hydatidiform mole
|
0.15%
1/663 • Number of events 2
|
0.00%
0/449
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder papilloma
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cerebellopontine angle tumour
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Intraductal proliferative breast lesion
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Non-small cell lung cancer metastatic
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Oesophageal carcinoma
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of the tongue
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
|
0.00%
0/267
|
0.59%
1/169 • Number of events 1
|
|
Nervous system disorders
Cerebral infarction
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Nervous system disorders
Cerebrovascular accident
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Nervous system disorders
Convulsion
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Nervous system disorders
Encephalopathy
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Nervous system disorders
Epilepsy
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Nervous system disorders
Headache
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Nervous system disorders
Hypoglycaemic seizure
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Nervous system disorders
Hypoglycaemic unconsciousness
|
0.60%
4/663 • Number of events 4
|
0.22%
1/449 • Number of events 1
|
|
Psychiatric disorders
Anxiety
|
0.00%
0/663
|
0.22%
1/449 • Number of events 2
|
|
Psychiatric disorders
Major depression
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Psychiatric disorders
Suicide attempt
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Renal and urinary disorders
Nephrotic syndrome
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Reproductive system and breast disorders
Ovarian cyst
|
0.00%
0/267
|
0.59%
1/169 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Asthma
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Eczema
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Skin and subcutaneous tissue disorders
Lipohypertrophy
|
0.30%
2/663 • Number of events 4
|
0.00%
0/449
|
|
Skin and subcutaneous tissue disorders
Skin ulcer
|
0.00%
0/663
|
0.22%
1/449 • Number of events 3
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Vascular disorders
Haemorrhage
|
0.15%
1/663 • Number of events 1
|
0.00%
0/449
|
|
Vascular disorders
Peripheral ischaemia
|
0.00%
0/663
|
0.22%
1/449 • Number of events 1
|
Other adverse events
| Measure |
LY2605541 + Insulin Lispro
n=663 participants at risk
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
Insulin Glargine + Insulin Lispro
n=449 participants at risk
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 52 weeks.
Participant-specific dose of Insulin Lispro was administered SC at meal times for 52 weeks.
|
|---|---|---|
|
Gastrointestinal disorders
Diarrhoea
|
2.1%
14/663 • Number of events 16
|
3.6%
16/449 • Number of events 17
|
|
Gastrointestinal disorders
Nausea
|
3.2%
21/663 • Number of events 27
|
3.8%
17/449 • Number of events 18
|
|
Gastrointestinal disorders
Vomiting
|
3.0%
20/663 • Number of events 20
|
3.6%
16/449 • Number of events 21
|
|
General disorders
Injection site hypertrophy
|
2.4%
16/663 • Number of events 20
|
0.00%
0/449
|
|
Infections and infestations
Bronchitis
|
2.4%
16/663 • Number of events 17
|
2.7%
12/449 • Number of events 14
|
|
Infections and infestations
Gastroenteritis
|
1.8%
12/663 • Number of events 15
|
2.4%
11/449 • Number of events 14
|
|
Infections and infestations
Gastroenteritis viral
|
2.7%
18/663 • Number of events 18
|
3.3%
15/449 • Number of events 15
|
|
Infections and infestations
Influenza
|
6.8%
45/663 • Number of events 47
|
4.9%
22/449 • Number of events 23
|
|
Infections and infestations
Nasopharyngitis
|
15.8%
105/663 • Number of events 141
|
15.6%
70/449 • Number of events 99
|
|
Infections and infestations
Sinusitis
|
4.4%
29/663 • Number of events 33
|
3.1%
14/449 • Number of events 19
|
|
Infections and infestations
Upper respiratory tract infection
|
9.2%
61/663 • Number of events 76
|
8.9%
40/449 • Number of events 52
|
|
Infections and infestations
Urinary tract infection
|
3.6%
24/663 • Number of events 28
|
3.3%
15/449 • Number of events 18
|
|
Infections and infestations
Viral infection
|
1.1%
7/663 • Number of events 9
|
2.7%
12/449 • Number of events 12
|
|
Investigations
Alanine aminotransferase increased
|
2.6%
17/663 • Number of events 17
|
0.67%
3/449 • Number of events 4
|
|
Investigations
Weight increased
|
2.3%
15/663 • Number of events 16
|
1.3%
6/449 • Number of events 6
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.1%
14/663 • Number of events 15
|
2.2%
10/449 • Number of events 12
|
|
Nervous system disorders
Headache
|
3.6%
24/663 • Number of events 37
|
3.1%
14/449 • Number of events 21
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
4.7%
31/663 • Number of events 32
|
3.1%
14/449 • Number of events 15
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
2.1%
14/663 • Number of events 15
|
2.7%
12/449 • Number of events 12
|
|
Skin and subcutaneous tissue disorders
Lipohypertrophy
|
8.3%
55/663 • Number of events 69
|
0.22%
1/449 • Number of events 1
|
|
Vascular disorders
Hypertension
|
1.7%
11/663 • Number of events 12
|
2.4%
11/449 • Number of events 11
|
Additional Information
Chief Medical Officer
Eli Lilly and Company
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60