Trial Outcomes & Findings for A Study in Participants With Type 2 Diabetes Mellitus (NCT NCT01468987)
NCT ID: NCT01468987
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 stratification factors (country, low-density lipoprotein cholesterol \[LDL-C, \<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
COMPLETED
PHASE3
1369 participants
Baseline, 26 weeks
2018-04-17
Participant Flow
Participant milestones
| Measure |
LY2605541 + Insulin Lispro
Includes participants that were randomized to receive LY2605541 plus Insulin Lispro.
Participant-specific dose of LY2605541 was administered subcutaneously (SC) once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial (pre-meal) and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
Includes participants that were randomized to receive Insulin Glargine plus Insulin Lispro.
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Overall Study
STARTED
|
691
|
678
|
|
Overall Study
Received at Least 1 Dose of Study Drug
|
691
|
677
|
|
Overall Study
COMPLETED
|
620
|
618
|
|
Overall Study
NOT COMPLETED
|
71
|
60
|
Reasons for withdrawal
| Measure |
LY2605541 + Insulin Lispro
Includes participants that were randomized to receive LY2605541 plus Insulin Lispro.
Participant-specific dose of LY2605541 was administered subcutaneously (SC) once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial (pre-meal) and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
Includes participants that were randomized to receive Insulin Glargine plus Insulin Lispro.
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Overall Study
Adverse Event
|
12
|
9
|
|
Overall Study
Death
|
4
|
1
|
|
Overall Study
Lost to Follow-up
|
10
|
5
|
|
Overall Study
Protocol Violation
|
8
|
2
|
|
Overall Study
Withdrawal by Subject
|
28
|
28
|
|
Overall Study
Physician Decision
|
8
|
15
|
|
Overall Study
Sponsor Decision
|
1
|
0
|
Baseline Characteristics
A Study in Participants With Type 2 Diabetes Mellitus
Baseline characteristics by cohort
| Measure |
LY2605541 + Insulin Lispro
n=691 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=678 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Total
n=1369 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
57.43 years
STANDARD_DEVIATION 9.21 • n=93 Participants
|
57.77 years
STANDARD_DEVIATION 9.17 • n=4 Participants
|
57.6 years
STANDARD_DEVIATION 9.19 • n=27 Participants
|
|
Sex: Female, Male
Female
|
315 Participants
n=93 Participants
|
274 Participants
n=4 Participants
|
589 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
376 Participants
n=93 Participants
|
404 Participants
n=4 Participants
|
780 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
74 Participants
n=93 Participants
|
78 Participants
n=4 Participants
|
152 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
452 Participants
n=93 Participants
|
427 Participants
n=4 Participants
|
879 Participants
n=27 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
165 Participants
n=93 Participants
|
173 Participants
n=4 Participants
|
338 Participants
n=27 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Asian
|
25 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
55 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
2 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
4 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Black or African American
|
42 Participants
n=93 Participants
|
50 Participants
n=4 Participants
|
92 Participants
n=27 Participants
|
|
Race (NIH/OMB)
White
|
615 Participants
n=93 Participants
|
585 Participants
n=4 Participants
|
1200 Participants
n=27 Participants
|
|
Race (NIH/OMB)
More than one race
|
5 Participants
n=93 Participants
|
9 Participants
n=4 Participants
|
14 Participants
n=27 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
|
Region of Enrollment
United States
|
276 Participants
n=93 Participants
|
270 Participants
n=4 Participants
|
546 Participants
n=27 Participants
|
|
Region of Enrollment
Taiwan
|
7 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Region of Enrollment
Slovakia
|
25 Participants
n=93 Participants
|
17 Participants
n=4 Participants
|
42 Participants
n=27 Participants
|
|
Region of Enrollment
Greece
|
12 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
23 Participants
n=27 Participants
|
|
Region of Enrollment
Spain
|
30 Participants
n=93 Participants
|
35 Participants
n=4 Participants
|
65 Participants
n=27 Participants
|
|
Region of Enrollment
Lithuania
|
4 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
6 Participants
n=27 Participants
|
|
Region of Enrollment
Turkey
|
4 Participants
n=93 Participants
|
7 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Region of Enrollment
Austria
|
9 Participants
n=93 Participants
|
6 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Region of Enrollment
Russia
|
19 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
39 Participants
n=27 Participants
|
|
Region of Enrollment
Israel
|
20 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
|
Region of Enrollment
United Kingdom
|
5 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
8 Participants
n=27 Participants
|
|
Region of Enrollment
Italy
|
16 Participants
n=93 Participants
|
16 Participants
n=4 Participants
|
32 Participants
n=27 Participants
|
|
Region of Enrollment
Czechia
|
23 Participants
n=93 Participants
|
22 Participants
n=4 Participants
|
45 Participants
n=27 Participants
|
|
Region of Enrollment
Hungary
|
36 Participants
n=93 Participants
|
36 Participants
n=4 Participants
|
72 Participants
n=27 Participants
|
|
Region of Enrollment
Mexico
|
13 Participants
n=93 Participants
|
12 Participants
n=4 Participants
|
25 Participants
n=27 Participants
|
|
Region of Enrollment
Puerto Rico
|
20 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
46 Participants
n=27 Participants
|
|
Region of Enrollment
Poland
|
20 Participants
n=93 Participants
|
20 Participants
n=4 Participants
|
40 Participants
n=27 Participants
|
|
Region of Enrollment
Brazil
|
11 Participants
n=93 Participants
|
13 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
|
Region of Enrollment
Romania
|
34 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
65 Participants
n=27 Participants
|
|
Region of Enrollment
Croatia
|
5 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
7 Participants
n=27 Participants
|
|
Region of Enrollment
Denmark
|
9 Participants
n=93 Participants
|
3 Participants
n=4 Participants
|
12 Participants
n=27 Participants
|
|
Region of Enrollment
Australia
|
26 Participants
n=93 Participants
|
25 Participants
n=4 Participants
|
51 Participants
n=27 Participants
|
|
Region of Enrollment
Netherlands
|
7 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
15 Participants
n=27 Participants
|
|
Region of Enrollment
Germany
|
50 Participants
n=93 Participants
|
54 Participants
n=4 Participants
|
104 Participants
n=27 Participants
|
|
Region of Enrollment
Japan
|
10 Participants
n=93 Participants
|
11 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: Baseline, 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 a 2 to 3 month timeframe. Least Squares (LS) means were calculated using mixed model repeated measures (MMRM) adjusting for stratification factors (country, low-density lipoprotein cholesterol \[LDL-C, \<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=684 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=672 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Change From Baseline in Hemoglobin A1c (HbA1c) at 26 Weeks
|
-1.66 percentage of HbA1c
Standard Error 0.04
|
-1.45 percentage of HbA1c
Standard Error 0.04
|
SECONDARY outcome
Timeframe: Baseline through 26 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 millimoles per liter \[mmol/L\]). 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=689 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=676 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Total Hypoglycemia Rates (Adjusted for 30 Days)
|
5.97 episodes/participant/30 days
Standard Error 0.20
|
5.42 episodes/participant/30 days
Standard Error 0.19
|
SECONDARY outcome
Timeframe: Baseline through 26 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 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=689 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=676 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Percentage of Participants With Total Hypoglycemia Episodes
|
95.2 percentage of participants
|
96.6 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline through 26 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 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=689 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=676 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Nocturnal Hypoglycemia Rates (Adjusted for 30 Days)
|
0.51 events/participant/30 days
Standard Error 0.03
|
0.92 events/participant/30 days
Standard Error 0.05
|
SECONDARY outcome
Timeframe: Baseline through 26 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 an event which is associated with 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=689 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=676 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Percentage of Participants With Nocturnal Hypoglycemia Episodes
|
59.5 percentage of participants
|
74.0 percentage of participants
|
SECONDARY outcome
Timeframe: Baseline, 26 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 stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment-by-visit interaction, and baseline body weight as fixed effects, and participant as a random effect.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=682 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=671 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Body Weight Change From Baseline to 26 Weeks
|
1.25 kilograms (kg)
Standard Error 0.16
|
2.21 kilograms (kg)
Standard Error 0.16
|
SECONDARY outcome
Timeframe: 26 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 nonconsecutive days within the week prior to Weeks 0, 4, 12, and 26. 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 stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline BG values.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=639 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=619 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
0300 hours
|
143.90 mg/dL
Standard Error 2.54
|
140.19 mg/dL
Standard Error 2.59
|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
Pre-morning meal
|
137.31 mg/dL
Standard Error 1.63
|
133.81 mg/dL
Standard Error 1.66
|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
2 hours post-morning meal
|
162.77 mg/dL
Standard Error 2.59
|
156.41 mg/dL
Standard Error 2.64
|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
Pre-midday meal
|
130.02 mg/dL
Standard Error 1.97
|
133.63 mg/dL
Standard Error 2.02
|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
2 hours post-midday meal
|
145.55 mg/dL
Standard Error 2.67
|
156.17 mg/dL
Standard Error 2.72
|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
Pre-evening meal
|
142.65 mg/dL
Standard Error 2.09
|
149.19 mg/dL
Standard Error 2.14
|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
2 hours post-evening meal
|
156.56 mg/dL
Standard Error 2.72
|
166.59 mg/dL
Standard Error 2.85
|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
Bedtime
|
160.15 mg/dL
Standard Error 2.60
|
163.62 mg/dL
Standard Error 2.70
|
|
Self-Monitored Blood Glucose (SMBG) 9-point Profiles at 26 Weeks
Pre-morning meal next day
|
135.09 mg/dL
Standard Error 1.77
|
132.07 mg/dL
Standard Error 1.81
|
SECONDARY outcome
Timeframe: up to 26 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=684 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=672 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Percentage of Participants With HbA1c <7.0% and ≤6.5% at 26 Weeks
HbA1c ≤6.5%
|
44.4 percentage of participants
|
32.6 percentage of participants
|
|
Percentage of Participants With HbA1c <7.0% and ≤6.5% at 26 Weeks
HbA1c <7.0%
|
63.3 percentage of participants
|
53.3 percentage of participants
|
SECONDARY outcome
Timeframe: up to 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data. Missing endpoints were imputed with the LOCF method, using only post-baseline data.
Hypoglycemic episodes are defined as an event which is 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=684 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=672 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Percentage of Participants With HbA1c <7.0% Without Nocturnal Hypoglycemia at 26 Weeks
|
23.7 percentage of participants
|
12.2 percentage of participants
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable insulin dose data.
Basal insulin dose, short-acting bolus insulin dose (each meal and overall), 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 post-baseline visit and stratification variables (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and baseline number of insulin injections \[1, 2, or ≥3\]).
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=615 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=613 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Basal, Bolus, and Total Insulin Dose by Weight at 26 Weeks
Basal Insulin
|
0.68 units/kg/day
Standard Error 0.01
|
0.60 units/kg/day
Standard Error 0.01
|
|
Basal, Bolus, and Total Insulin Dose by Weight at 26 Weeks
Bolus Insulin
|
0.61 units/kg/day
Standard Error 0.02
|
0.63 units/kg/day
Standard Error 0.02
|
|
Basal, Bolus, and Total Insulin Dose by Weight at 26 Weeks
Total Insulin
|
1.27 units/kg/day
Standard Error 0.02
|
1.21 units/kg/day
Standard Error 0.02
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable FSG data at both baseline and post-baseline.
LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment-by-visit interaction, and baseline FSG.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=683 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=672 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Fasting Serum Glucose (FSG) From Laboratory at 26 Weeks
|
125.33 mg/dL
Standard Error 1.93
|
132.02 mg/dL
Standard Error 1.94
|
SECONDARY outcome
Timeframe: 26 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 self-monitored blood glucose (SMBG). Between-day glucose variability is measured by the standard deviation of FBG. LS means were calculated using MMRM adjusting for the stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment-by-visit interaction, and baseline FBG variability.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=674 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=652 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Fasting Blood Glucose (FBG) (by SMBG) Intra-participant Variability at 26 Weeks
|
28.67 mg/dL
Standard Error 0.79
|
33.54 mg/dL
Standard Error 0.80
|
SECONDARY outcome
Timeframe: 26 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 SMBG profiles with both 0300 hours and the next day pre-morning measurements are included for the calculation of such excursion). LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment-by-visit interaction, and baseline excursion.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=470 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=450 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
0300-hour Blood Glucose to FBG Excursion at 26 Weeks
|
-11.95 mg/dL
Standard Error 2.34
|
-15.16 mg/dL
Standard Error 2.37
|
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 stratification factors (country, LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and number of insulin injections at baseline \[1, 2, or ≥3\]), treatment, visit, treatment, visit-by-treatment interaction, and baseline HbA1c.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=684 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=672 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
HbA1c at 26 Weeks
|
6.76 percentage of HbA1c
Standard Error 0.04
|
6.97 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 lipid data at both baseline and post-baseline.
Concentrations of cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and triglycerides are summarized. LS means were calculated using MMRM adjusting for stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, LDL-C \[\<100 mg/dL and ≥100 mg/dL\], except for the LDL-C outcome variable\], number of insulin injections at baseline \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=684 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=674 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Lipid Profile at 26 Weeks
Cholesterol
|
177.17 mg/dL
Standard Error 1.13
|
174.79 mg/dL
Standard Error 1.14
|
|
Lipid Profile at 26 Weeks
HDL-C
|
46.44 mg/dL
Standard Error 0.27
|
47.71 mg/dL
Standard Error 0.27
|
|
Lipid Profile at 26 Weeks
LDL-C
|
97.87 mg/dL
Standard Error 0.99
|
98.89 mg/dL
Standard Error 0.99
|
|
Lipid Profile at 26 Weeks
Triglycerides
|
168.79 mg/dL
Standard Error 2.85
|
141.78 mg/dL
Standard Error 2.86
|
SECONDARY outcome
Timeframe: Baseline through 26 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 number of participants with a treatment-emergent anti-LY2605541 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=682 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=672 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Number of Participants With Change in Anti-LY2605541 Antibodies From Baseline to 26 Weeks
|
152 participants
|
161 participants
|
SECONDARY outcome
Timeframe: up to 26 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.
ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, Insulin Delivery Device. Data presented are the transformed overall score on a scale of 0-100, where higher scores indicate better treatment satisfaction. LS means were calculated using an analysis of covariance (ANCOVA) model with treatment and stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, and baseline number of insulin injections \[1, 2, or ≥3\]) as fixed effects and baseline value of the ITSQ scores as a covariate.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=631 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=637 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Insulin Treatment Satisfaction Questionnaire (ITSQ) at 26 Weeks
|
77.01 units on a scale
Standard Error 0.55
|
77.29 units on a scale
Standard Error 0.54
|
SECONDARY outcome
Timeframe: 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable LBSS data at both baseline and post-baseline.
LBSS (also referenced as Hypoglycemia Fear Survey - II \[HFS-II\]) is a 33-item 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 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 including stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, baseline number of insulin injections \[1, 2, or ≥3\]), visit, treatment, visit-by-treatment interaction, and baseline LBSS score.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=682 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=671 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Low Blood Sugar Survey (LBSS) at 26 Weeks
|
21.44 units on a scale
Standard Error 0.56
|
21.67 units on a scale
Standard Error 0.56
|
SECONDARY outcome
Timeframe: up to 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable EQ-5D data at both baseline and post-baseline. Missing endpoints were imputed with the LOCF method.
The EQ-5D 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 ANCOVA adjusting for treatment, stratification factors (baseline HbA1c \[≤8.5% and \>8.5%\], country, and baseline number of insulin injections \[1, 2, or ≥ 3\]), and baseline EQ-5D score.
Outcome measures
| Measure |
LY2605541 + Insulin Lispro
n=636 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=644 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
EuroQoL-5D (EQ-5D) at 26 Weeks
|
0.86 units on a scale
Standard Error 0.00
|
0.85 units on a scale
Standard Error 0.00
|
SECONDARY outcome
Timeframe: up to 26 weeksPopulation: Participants who were randomized, had at least 1 dose of study medication, and had evaluable RAPA data. Missing endpoints were imputed with the LOCF method, using only post-baseline 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 activities, 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=331 Participants
Participant-specific dose of LY2605541 was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=346 Participants
Participant-specific dose of Insulin Glargine was administered SC once daily at bedtime for 26 weeks.
Participant-specific dose of Insulin Lispro was administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
RAPA 1, Sedentary
|
2.2 percentage of participants
|
2.4 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
RAPA 1, Light activity
|
21.9 percentage of participants
|
18.0 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
RAPA 1, Regular underactive
|
32.7 percentage of participants
|
27.1 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
RAPA 1, Active
|
38.6 percentage of participants
|
46.3 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
RAPA 2, Neither strength/flexibility
|
58.3 percentage of participants
|
53.8 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
RAPA 2, Either strength/flexibility
|
28.1 percentage of participants
|
30.6 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
RAPA 2, Both strength/flexibility
|
13.6 percentage of participants
|
15.6 percentage of participants
|
|
Rapid Assessment of Physical Activity (RAPA) at 26 Weeks
RAPA 1, Underactive
|
4.6 percentage of participants
|
6.2 percentage of participants
|
Adverse Events
LY2605541 + Insulin Lispro
Insulin Glargine + Insulin Lispro
Serious adverse events
| Measure |
LY2605541 + Insulin Lispro
n=691 participants at risk
Participant-specific doses of LY2605541 were administered SC once daily at bedtime for 26 weeks.
Participant-specific doses of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=677 participants at risk
Participant-specific doses of Insulin Glargine were administered SC once daily at bedtime for 26 weeks.
Participant-specific doses of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
Cardiac disorders
Acute myocardial infarction
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
Cardiac disorders
Angina pectoris
|
0.14%
1/691 • Number of events 1
|
0.30%
2/677 • Number of events 2
|
|
Cardiac disorders
Angina unstable
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
Cardiac disorders
Atrial fibrillation
|
0.29%
2/691 • Number of events 2
|
0.15%
1/677 • Number of events 2
|
|
Cardiac disorders
Cardiac arrest
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Cardiac disorders
Cardiac failure
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Cardiac disorders
Cardiac failure acute
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Cardiac disorders
Cardio-respiratory arrest
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Cardiac disorders
Coronary artery disease
|
0.43%
3/691 • Number of events 4
|
0.30%
2/677 • Number of events 2
|
|
Cardiac disorders
Coronary artery stenosis
|
0.43%
3/691 • Number of events 3
|
0.00%
0/677
|
|
Cardiac disorders
Hypertensive heart disease
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Cardiac disorders
Myocardial infarction
|
0.29%
2/691 • Number of events 2
|
0.15%
1/677 • Number of events 1
|
|
Cardiac disorders
Nodal arrhythmia
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Cardiac disorders
Ventricular tachycardia
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Ear and labyrinth disorders
Inner ear disorder
|
0.14%
1/691 • Number of events 2
|
0.00%
0/677
|
|
Ear and labyrinth disorders
Vertigo
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Endocrine disorders
Hyperparathyroidism primary
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Eye disorders
Cataract
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Eye disorders
Panophthalmitis
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Gastrointestinal disorders
Abdominal pain
|
0.00%
0/691
|
0.30%
2/677 • Number of events 2
|
|
Gastrointestinal disorders
Anal fistula
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Gastrointestinal disorders
Bezoar
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Gastrointestinal disorders
Crohn's disease
|
0.14%
1/691 • Number of events 2
|
0.00%
0/677
|
|
Gastrointestinal disorders
Diarrhoea
|
0.14%
1/691 • Number of events 3
|
0.00%
0/677
|
|
Gastrointestinal disorders
Haematochezia
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Gastrointestinal disorders
Inguinal hernia
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Gastrointestinal disorders
Large intestine polyp
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Gastrointestinal disorders
Oesophagitis
|
0.14%
1/691 • Number of events 3
|
0.00%
0/677
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/691
|
0.15%
1/677 • Number of events 2
|
|
Gastrointestinal disorders
Small intestinal obstruction
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Gastrointestinal disorders
Umbilical hernia
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
General disorders
Chest pain
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
General disorders
Death
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
General disorders
Medical device complication
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
General disorders
Non-cardiac chest pain
|
0.29%
2/691 • Number of events 2
|
0.00%
0/677
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Hepatobiliary disorders
Drug-induced liver injury
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Hepatobiliary disorders
Hepatic cirrhosis
|
0.00%
0/691
|
0.15%
1/677 • Number of events 2
|
|
Immune system disorders
Anaphylactic shock
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Immune system disorders
Drug hypersensitivity
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Immune system disorders
Hypersensitivity
|
0.00%
0/691
|
0.30%
2/677 • Number of events 2
|
|
Immune system disorders
Sarcoidosis
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Infections and infestations
Appendicitis
|
0.29%
2/691 • Number of events 2
|
0.00%
0/677
|
|
Infections and infestations
Bronchitis
|
0.29%
2/691 • Number of events 2
|
0.15%
1/677 • Number of events 2
|
|
Infections and infestations
Cellulitis
|
0.43%
3/691 • Number of events 6
|
0.15%
1/677 • Number of events 1
|
|
Infections and infestations
Diabetic foot infection
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
Infections and infestations
Enterococcal infection
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Infections and infestations
Incision site infection
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Infections and infestations
Infected skin ulcer
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Infections and infestations
Infectious mononucleosis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Infections and infestations
Osteomyelitis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Infections and infestations
Pneumonia
|
0.43%
3/691 • Number of events 3
|
0.44%
3/677 • Number of events 3
|
|
Infections and infestations
Rotavirus infection
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Infections and infestations
Subcutaneous abscess
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Infections and infestations
Viral infection
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Infections and infestations
Wound infection
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Acetabulum fracture
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Bone contusion
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Contusion
|
0.14%
1/691 • Number of events 2
|
0.15%
1/677 • Number of events 1
|
|
Injury, poisoning and procedural complications
Coronary artery restenosis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Excoriation
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Fall
|
0.14%
1/691 • Number of events 1
|
0.30%
2/677 • Number of events 2
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Injury, poisoning and procedural complications
Head injury
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Injury
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Lower limb fracture
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Injury, poisoning and procedural complications
Medication error
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Road traffic accident
|
0.29%
2/691 • Number of events 2
|
0.30%
2/677 • Number of events 2
|
|
Injury, poisoning and procedural complications
Skull fractured base
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Injury, poisoning and procedural complications
Subdural haematoma
|
0.00%
0/691
|
0.30%
2/677 • Number of events 3
|
|
Injury, poisoning and procedural complications
Tibia fracture
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Traumatic haematoma
|
0.14%
1/691 • Number of events 2
|
0.00%
0/677
|
|
Injury, poisoning and procedural complications
Upper limb fracture
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
Investigations
Catheterisation cardiac
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Metabolism and nutrition disorders
Fluid overload
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
2.6%
18/691 • Number of events 21
|
1.8%
12/677 • Number of events 15
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.14%
1/691 • Number of events 2
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Bursitis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Exostosis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
Musculoskeletal and connective tissue disorders
Mobility decreased
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Rhabdomyolysis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome
|
0.14%
1/691 • Number of events 2
|
0.00%
0/677
|
|
Musculoskeletal and connective tissue disorders
Spinal column stenosis
|
0.00%
0/691
|
0.30%
2/677 • Number of events 5
|
|
Musculoskeletal and connective tissue disorders
Spinal disorder
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
|
0.00%
0/691
|
0.30%
2/677 • Number of events 2
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Large intestine benign neoplasm
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Ovarian cancer
|
0.32%
1/315 • Number of events 1
|
0.00%
0/273
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
|
0.27%
1/376 • Number of events 1
|
0.00%
0/404
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer metastatic
|
0.00%
0/376
|
0.25%
1/404 • Number of events 1
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Rectal adenocarcinoma
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Nervous system disorders
Carotid artery stenosis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Nervous system disorders
Diabetic hyperosmolar coma
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Nervous system disorders
Hypoglycaemic unconsciousness
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Nervous system disorders
Ischaemic stroke
|
0.29%
2/691 • Number of events 2
|
0.00%
0/677
|
|
Nervous system disorders
Transient ischaemic attack
|
0.43%
3/691 • Number of events 3
|
0.15%
1/677 • Number of events 1
|
|
Psychiatric disorders
Adjustment disorder
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Psychiatric disorders
Depression
|
0.29%
2/691 • Number of events 4
|
0.00%
0/677
|
|
Psychiatric disorders
Panic attack
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Renal and urinary disorders
Calculus ureteric
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Renal and urinary disorders
Nephrolithiasis
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/691
|
0.30%
2/677 • Number of events 2
|
|
Renal and urinary disorders
Renal failure chronic
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Renal and urinary disorders
Urinary tract obstruction
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Reproductive system and breast disorders
Postmenopausal haemorrhage
|
0.00%
0/315
|
0.37%
1/273 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea exertional
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
|
0.00%
0/691
|
0.15%
1/677 • Number of events 2
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Skin and subcutaneous tissue disorders
Blister
|
0.14%
1/691 • Number of events 2
|
0.00%
0/677
|
|
Surgical and medical procedures
Coronary arterial stent insertion
|
0.14%
1/691 • Number of events 1
|
0.15%
1/677 • Number of events 1
|
|
Surgical and medical procedures
Knee arthroplasty
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Vascular disorders
Deep vein thrombosis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Vascular disorders
Hypertensive crisis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Vascular disorders
Intermittent claudication
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
|
Vascular disorders
Peripheral arterial occlusive disease
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Vascular disorders
Subclavian artery stenosis
|
0.14%
1/691 • Number of events 1
|
0.00%
0/677
|
|
Vascular disorders
Venous insufficiency
|
0.00%
0/691
|
0.15%
1/677 • Number of events 1
|
Other adverse events
| Measure |
LY2605541 + Insulin Lispro
n=691 participants at risk
Participant-specific doses of LY2605541 were administered SC once daily at bedtime for 26 weeks.
Participant-specific doses of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks.
|
Insulin Glargine + Insulin Lispro
n=677 participants at risk
Participant-specific doses of Insulin Glargine were administered SC once daily at bedtime for 26 weeks.
Participant-specific doses of Insulin Lispro were administered SC for preprandial and supplemental doses for 26 weeks.
|
|---|---|---|
|
Eye disorders
Diabetic retinopathy
|
1.0%
7/691 • Number of events 8
|
0.74%
5/677 • Number of events 5
|
|
Gastrointestinal disorders
Abdominal pain
|
1.0%
7/691 • Number of events 7
|
0.59%
4/677 • Number of events 4
|
|
Gastrointestinal disorders
Constipation
|
1.3%
9/691 • Number of events 9
|
0.89%
6/677 • Number of events 6
|
|
Gastrointestinal disorders
Diarrhoea
|
3.5%
24/691 • Number of events 27
|
2.8%
19/677 • Number of events 22
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
1.0%
7/691 • Number of events 7
|
0.59%
4/677 • Number of events 4
|
|
Gastrointestinal disorders
Nausea
|
2.3%
16/691 • Number of events 16
|
1.3%
9/677 • Number of events 10
|
|
Gastrointestinal disorders
Vomiting
|
1.6%
11/691 • Number of events 11
|
1.5%
10/677 • Number of events 13
|
|
General disorders
Asthenia
|
0.00%
0/691
|
1.0%
7/677 • Number of events 7
|
|
General disorders
Fatigue
|
0.87%
6/691 • Number of events 8
|
2.4%
16/677 • Number of events 16
|
|
General disorders
Oedema peripheral
|
1.6%
11/691 • Number of events 11
|
3.8%
26/677 • Number of events 31
|
|
General disorders
Pyrexia
|
1.2%
8/691 • Number of events 8
|
1.0%
7/677 • Number of events 7
|
|
Infections and infestations
Bronchitis
|
2.9%
20/691 • Number of events 21
|
3.0%
20/677 • Number of events 22
|
|
Infections and infestations
Gastroenteritis
|
1.2%
8/691 • Number of events 9
|
2.4%
16/677 • Number of events 16
|
|
Infections and infestations
Gastroenteritis viral
|
1.7%
12/691 • Number of events 12
|
0.89%
6/677 • Number of events 6
|
|
Infections and infestations
Influenza
|
2.6%
18/691 • Number of events 19
|
2.4%
16/677 • Number of events 17
|
|
Infections and infestations
Nasopharyngitis
|
7.1%
49/691 • Number of events 58
|
9.3%
63/677 • Number of events 69
|
|
Infections and infestations
Pharyngitis
|
0.43%
3/691 • Number of events 3
|
1.0%
7/677 • Number of events 7
|
|
Infections and infestations
Sinusitis
|
2.3%
16/691 • Number of events 19
|
1.8%
12/677 • Number of events 13
|
|
Infections and infestations
Upper respiratory tract infection
|
4.2%
29/691 • Number of events 33
|
4.7%
32/677 • Number of events 39
|
|
Infections and infestations
Urinary tract infection
|
2.6%
18/691 • Number of events 19
|
3.4%
23/677 • Number of events 26
|
|
Injury, poisoning and procedural complications
Contusion
|
0.58%
4/691 • Number of events 6
|
1.2%
8/677 • Number of events 9
|
|
Injury, poisoning and procedural complications
Muscle strain
|
0.43%
3/691 • Number of events 3
|
1.0%
7/677 • Number of events 9
|
|
Investigations
Alanine aminotransferase increased
|
1.6%
11/691 • Number of events 12
|
0.30%
2/677 • Number of events 3
|
|
Investigations
Aspartate aminotransferase increased
|
1.0%
7/691 • Number of events 7
|
0.15%
1/677 • Number of events 1
|
|
Investigations
Blood creatine phosphokinase increased
|
0.29%
2/691 • Number of events 2
|
1.3%
9/677 • Number of events 9
|
|
Investigations
Weight increased
|
0.72%
5/691 • Number of events 5
|
1.2%
8/677 • Number of events 8
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
2.2%
15/691 • Number of events 17
|
2.2%
15/677 • Number of events 20
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
3.2%
22/691 • Number of events 25
|
3.4%
23/677 • Number of events 25
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
|
0.87%
6/691 • Number of events 7
|
1.2%
8/677 • Number of events 10
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.4%
10/691 • Number of events 10
|
2.1%
14/677 • Number of events 14
|
|
Nervous system disorders
Carpal tunnel syndrome
|
1.4%
10/691 • Number of events 11
|
0.15%
1/677 • Number of events 1
|
|
Nervous system disorders
Dizziness
|
1.3%
9/691 • Number of events 11
|
1.5%
10/677 • Number of events 10
|
|
Nervous system disorders
Headache
|
1.7%
12/691 • Number of events 12
|
2.8%
19/677 • Number of events 20
|
|
Nervous system disorders
Hypoaesthesia
|
1.0%
7/691 • Number of events 8
|
1.0%
7/677 • Number of events 9
|
|
Psychiatric disorders
Depression
|
0.58%
4/691 • Number of events 4
|
1.0%
7/677 • Number of events 7
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
1.6%
11/691 • Number of events 11
|
1.8%
12/677 • Number of events 12
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.72%
5/691 • Number of events 5
|
1.0%
7/677 • Number of events 7
|
|
Skin and subcutaneous tissue disorders
Lipohypertrophy
|
1.3%
9/691 • Number of events 11
|
0.00%
0/677
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
1.0%
7/691 • Number of events 7
|
0.15%
1/677 • Number of events 1
|
|
Skin and subcutaneous tissue disorders
Rash
|
1.3%
9/691 • Number of events 9
|
1.0%
7/677 • Number of events 8
|
|
Vascular disorders
Hypertension
|
2.0%
14/691 • Number of events 16
|
1.8%
12/677 • Number of events 12
|
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