Trial Outcomes & Findings for A Study for Patients With Type 2 Diabetes (NCT NCT01027871)

NCT ID: NCT01027871

Last Updated: 2018-06-08

Results Overview

8-point SMBG profiles are measured at morning FBG, midday and evening pre-meal blood glucose (BG), 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. Least squares (LS) mean of the FBG is from mixed-model repeated measures (MMRM) approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-interim analysis \[IA\], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline hemoglobin A1c \[HbA1c\] group); visit; visit and treatment interaction; random effect for participant.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

289 participants

Primary outcome timeframe

Week 12

Results posted on

2018-06-08

Participant Flow

Participant milestones

Participant milestones
Measure
Insulin Glargine
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
Participants took both LY2605541 and their pre-study insulin for first several days
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled
Overall Study
STARTED
93
98
98
Overall Study
Received at Least One Dose of Study Drug
93
98
97
Overall Study
COMPLETED
91
85
91
Overall Study
NOT COMPLETED
2
13
7

Reasons for withdrawal

Reasons for withdrawal
Measure
Insulin Glargine
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
Participants took both LY2605541 and their pre-study insulin for first several days
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled
Overall Study
Physician Decision
1
5
0
Overall Study
Protocol Violation
0
2
2
Overall Study
Withdrawal by Subject
1
2
2
Overall Study
Adverse Event
0
2
2
Overall Study
Sponsor Decision
0
2
0
Overall Study
Discontinued Prior to Treatment
0
0
1

Baseline Characteristics

A Study for Patients With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Insulin Glargine
n=93 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=98 Participants
Participants took both LY2605541 and their pre-study insulin for first several days
LY2605541 Algrithm 2
n=97 Participants
Participants took only LY2605541 with first dose doubled
Total
n=288 Participants
Total of all reporting groups
Age, Continuous
60.74 years
STANDARD_DEVIATION 7.94 • n=5 Participants
58.57 years
STANDARD_DEVIATION 9.99 • n=7 Participants
59.23 years
STANDARD_DEVIATION 9.28 • n=5 Participants
59.49 years
STANDARD_DEVIATION 9.14 • n=4 Participants
Sex: Female, Male
Female
46 Participants
n=5 Participants
41 Participants
n=7 Participants
48 Participants
n=5 Participants
135 Participants
n=4 Participants
Sex: Female, Male
Male
47 Participants
n=5 Participants
57 Participants
n=7 Participants
49 Participants
n=5 Participants
153 Participants
n=4 Participants
Race/Ethnicity, Customized
American Indian or Alaska Native
1 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
Race/Ethnicity, Customized
Asian
0 Participants
n=5 Participants
4 Participants
n=7 Participants
2 Participants
n=5 Participants
6 Participants
n=4 Participants
Race/Ethnicity, Customized
Black or African American
4 Participants
n=5 Participants
2 Participants
n=7 Participants
6 Participants
n=5 Participants
12 Participants
n=4 Participants
Race/Ethnicity, Customized
Multiple
1 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
1 Participants
n=4 Participants
Race/Ethnicity, Customized
White
87 Participants
n=5 Participants
0 Participants
n=7 Participants
0 Participants
n=5 Participants
87 Participants
n=4 Participants
Region of Enrollment
United States
23 Participants
n=5 Participants
31 Participants
n=7 Participants
37 Participants
n=5 Participants
91 Participants
n=4 Participants
Region of Enrollment
Hungary
5 Participants
n=5 Participants
5 Participants
n=7 Participants
6 Participants
n=5 Participants
16 Participants
n=4 Participants
Region of Enrollment
Puerto Rico
12 Participants
n=5 Participants
8 Participants
n=7 Participants
9 Participants
n=5 Participants
29 Participants
n=4 Participants
Region of Enrollment
Poland
0 Participants
n=5 Participants
2 Participants
n=7 Participants
2 Participants
n=5 Participants
4 Participants
n=4 Participants
Region of Enrollment
Spain
13 Participants
n=5 Participants
11 Participants
n=7 Participants
12 Participants
n=5 Participants
36 Participants
n=4 Participants
Region of Enrollment
Romania
12 Participants
n=5 Participants
13 Participants
n=7 Participants
12 Participants
n=5 Participants
37 Participants
n=4 Participants
Region of Enrollment
Australia
10 Participants
n=5 Participants
5 Participants
n=7 Participants
6 Participants
n=5 Participants
21 Participants
n=4 Participants
Region of Enrollment
Russia
18 Participants
n=5 Participants
13 Participants
n=7 Participants
12 Participants
n=5 Participants
43 Participants
n=4 Participants

PRIMARY outcome

Timeframe: Week 12

Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.

8-point SMBG profiles are measured at morning FBG, midday and evening pre-meal blood glucose (BG), 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. Least squares (LS) mean of the FBG is from mixed-model repeated measures (MMRM) approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-interim analysis \[IA\], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline hemoglobin A1c \[HbA1c\] group); visit; visit and treatment interaction; random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=89 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=86 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=91 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles
6.83 millimoles per Liter (mmol/L)
Standard Error 0.22
7.15 millimoles per Liter (mmol/L)
Standard Error 0.22
6.84 millimoles per Liter (mmol/L)
Standard Error 0.22

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.

FBG is measured by 8-point SMBG profiles, which are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean of the change from baseline to 12 weeks is from MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=89 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=177 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint
-1.77 mmol/Liter
Standard Error 0.26
-1.97 mmol/Liter
Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.

HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 dose algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=91 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=176 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Endpoint
-0.64 percentage of glycated hemoglobin
Standard Error 0.08
-0.74 percentage of glycated hemoglobin
Standard Error 0.06

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who took at least one dose of study drug, last observation carried forward (LOCF). Arms are combined due to

HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=91 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=183 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint
HbA1c <7.0%
48.4 percentage of participants
51.9 percentage of participants
Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint
HbA1c ≤6.5%
23.1 percentage of participants
29.5 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who took at least one dose of study drug, last observation carried forward (LOCF). Arms are combined due to

HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 millimole/Liter (mmol/L) (≤70 milligram/deciliter \[mg/dL\]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=92 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=188 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment
HbA1c <7.0%
11.96 percentage of participants
16.49 percentage of participants
Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment
HbA1c ≤6.5%
6.52 percentage of participants
7.98 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.

8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=92 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=191 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
Morning 2-hr postprandial BG
9.54 mmol/L
Standard Error 0.31
9.11 mmol/L
Standard Error 0.25
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
Midday Pre-meal BG
7.47 mmol/L
Standard Error 0.28
7.23 mmol/L
Standard Error 0.23
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
Midday 2-hr postprandial BG
9.49 mmol/L
Standard Error 0.28
9.22 mmol/L
Standard Error 0.22
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
Evening Pre-meal BG
7.92 mmol/L
Standard Error 0.28
7.80 mmol/L
Standard Error 0.22
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
Evening 2-hr postprandial BG
9.99 mmol/L
Standard Error 0.30
9.74 mmol/L
Standard Error 0.24
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
Bed time BG
9.44 mmol/L
Standard Error 0.31
9.15 mmol/L
Standard Error 0.25
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
0300 hours BG
7.26 mmol/L
Standard Error 0.25
7.36 mmol/L
Standard Error 0.20

SECONDARY outcome

Timeframe: Week 2 and Week 12

Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.

LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=92 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=188 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Daily Basal Insulin Dose at Week 2 and Week 12
Week 2
2.45 nanomole per kilogram (nmol/kg)
Standard Error 0.15
3.19 nanomole per kilogram (nmol/kg)
Standard Error 0.12
Daily Basal Insulin Dose at Week 2 and Week 12
Week 12
2.90 nanomole per kilogram (nmol/kg)
Standard Error 0.19
4.58 nanomole per kilogram (nmol/kg)
Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: All randomized participants who took at least one dose of study drug.

Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=93 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=195 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Percentage of Participants With Hypoglycemia From Baseline Through Week 12
63.4 percentage of participants
54.0 percentage of participants

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: All randomized participants who took at least one dose of study drug.

Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk\*30.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=93 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=195 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12
1.52 Number of Hypoglycemia episodes/30 days
Standard Deviation 2.08
1.34 Number of Hypoglycemia episodes/30 days
Standard Deviation 2.47

SECONDARY outcome

Timeframe: Week 12 and Week 16

Population: All randomized participants who took at least one dose of study drug with both baseline and endpoint antibody measurements.

Negative is defined as either 'negative' from lab or percent binding \<1.16%. Positive is defined as the percent binding is ≥1.16%. The antibody status change is from negative to positive or positive to negative.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=93 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=98 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=97 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16
Week 12 from negative to positive
2.4 percentage of participants
4.7 percentage of participants
2.8 percentage of participants
Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16
Week 12 from positive to negative
2.4 percentage of participants
0.0 percentage of participants
1.1 percentage of participants
Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16
Week 16 from negative to positive
2.4 percentage of participants
4.9 percentage of participants
3.5 percentage of participants
Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16
Week 16 from positive to negative
2.4 percentage of participants
0.0 percentage of participants
1.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week12

Population: All randomized participants who took at least one dose of study drug with non-missing baseline value and at least one non-missing post-baseline value.

Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=92 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=191 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12
Baseline
1.52 nmol/L
Standard Error 0.11
1.51 nmol/L
Standard Error 0.09
Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12
Week 12
1.23 nmol/L
Standard Error 0.08
1.20 nmol/L
Standard Error 0.06

SECONDARY outcome

Timeframe: Week 12

Population: Participants who took at least one dose of study drug and had measurements at Week 12.

The drug (LY2605541) concentration at steady state (Css) is calculated from the clearance (Liter/hour) and the final dose of the participants. Clearance was estimated using population-based approaches.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=177 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 12 Endpoint
4258 picomoles per liter (pMol/L)
Geometric Coefficient of Variation 70.8

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.

FBG is measured by 8-point SMBG profiles, which are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean of the change from baseline to 12 weeks is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=89 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=70 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=78 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
-1.82 nmol/L
Standard Error 0.23
-2.22 nmol/L
Standard Error 0.24
-1.99 nmol/L
Standard Error 0.23

SECONDARY outcome

Timeframe: Baseline, Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.

HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=91 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=69 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=78 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
-0.65 percentage of glycated hemoglobin
Standard Error 0.07
-0.67 percentage of glycated hemoglobin
Standard Error 0.07
-0.83 percentage of glycated hemoglobin
Standard Error 0.07

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, last observation carried forward (LOCF).

HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=91 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=73 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=80 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
HbA1c <7.0%
48.4 percentage of participants
57.5 percentage of participants
50 percentage of participants
Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
HbA1c ≤6.5%
23.1 percentage of participants
31.5 percentage of participants
26.3 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, last observation carried forward (LOCF).

HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=92 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=75 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=83 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
HbA1c <7.0%
11.96 percentage of participants
21.33 percentage of participants
15.66 percentage of participants
Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
HbA1c ≤6.5%
6.52 percentage of participants
9.33 percentage of participants
7.23 percentage of participants

SECONDARY outcome

Timeframe: Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.

8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=92 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=78 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=83 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Midday Pre-meal BG
7.29 nmol/L
Standard Error 0.26
7.22 nmol/L
Standard Error 0.27
6.60 nmol/L
Standard Error 0.26
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
0300 hours BG
7.10 nmol/L
Standard Error 0.22
7.34 nmol/L
Standard Error 0.24
6.82 nmol/L
Standard Error 0.23
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Morning pre-meal BG
6.76 nmol/L
Standard Error 0.19
7.02 nmol/L
Standard Error 0.21
6.62 nmol/L
Standard Error 0.20
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Morning 2-hr postprandial BG
9.31 nmol/L
Standard Error 0.27
9.05 nmol/L
Standard Error 0.29
8.48 nmol/L
Standard Error 0.28
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Midday 2-hr postprandial BG
9.36 nmol/L
Standard Error 0.25
8.96 nmol/L
Standard Error 0.27
9.09 nmol/L
Standard Error 0.26
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Evening Pre-meal BG
7.79 nmol/L
Standard Error 0.25
7.64 nmol/L
Standard Error 0.27
7.64 nmol/L
Standard Error 0.25
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Evening 2-hr postprandial BG
9.64 nmol/L
Standard Error 0.26
9.14 nmol/L
Standard Error 0.28
9.22 nmol/L
Standard Error 0.27
8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Bed time BG
9.13 nmol/L
Standard Error 0.27
8.86 nmol/L
Standard Error 0.29
8.43 nmol/L
Standard Error 0.28

SECONDARY outcome

Timeframe: Week 2 and Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.

LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=92 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=76 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=81 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Week 2
2.62 nmol/kg
Standard Error 0.13
3.23 nmol/kg
Standard Error 0.13
3.64 nmol/kg
Standard Error 0.13
Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Week 12
3.15 nmol/kg
Standard Error 0.16
4.58 nmol/kg
Standard Error 0.17
5.26 nmol/kg
Standard Error 0.17

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance.

Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]).

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=93 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=80 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=83 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
63.4 percentage of participants
47.5 percentage of participants
54.2 percentage of participants

SECONDARY outcome

Timeframe: Baseline through Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance.

Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines \[ADA 2005\]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk\*30.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=93 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=80 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=83 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
1.52 Number of Hypoglycemia episodes/30 days
Standard Deviation 2.08
1.25 Number of Hypoglycemia episodes/30 days
Standard Deviation 2.27
1.27 Number of Hypoglycemia episodes/30 days
Standard Deviation 2.20

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: All randomized participants who took at least one dose of study drug, excluding those on LY2605541 prior to the changes in the dosing guidance, with non-missing baseline value and at least one non-missing post-baseline value.

Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; interaction between visit and treatment; and a random effect for participant.

Outcome measures

Outcome measures
Measure
Insulin Glargine
n=92 Participants
Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 1
n=77 Participants
Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Algorithm 2
n=83 Participants
Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Baseline
1.43 nmol/L
Standard Error 0.07
1.40 nmol/L
Standard Error 0.08
1.42 nmol/L
Standard Error 0.07
Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Week 12
1.17 nmol/L
Standard Error 0.07
1.16 nmol/L
Standard Error 0.08
1.07 nmol/L
Standard Error 0.07

Adverse Events

LY2605541 Dosing Algorithm 1

Serious events: 4 serious events
Other events: 44 other events
Deaths: 0 deaths

LY2605541 Dosing Algorithm 2

Serious events: 1 serious events
Other events: 47 other events
Deaths: 0 deaths

Insulin Glargine

Serious events: 2 serious events
Other events: 45 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
LY2605541 Dosing Algorithm 1
n=98 participants at risk
subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Dosing Algorithm 2
n=98 participants at risk
subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Insulin Glargine
n=93 participants at risk
Subcutaneous injection of insulin Glargine every morning with dose titration based on blood glucose measures for 12 weeks
Cardiac disorders
Angina unstable
1.0%
1/98 • Number of events 1
1.0%
1/98 • Number of events 1
1.1%
1/93 • Number of events 1
Cardiac disorders
Coronary artery disease
0.00%
0/98
0.00%
0/98
1.1%
1/93 • Number of events 1
Cardiac disorders
Myocardial infarction
1.0%
1/98 • Number of events 1
1.0%
1/98 • Number of events 1
0.00%
0/93
Hepatobiliary disorders
Cholecystitis
1.0%
1/98 • Number of events 1
0.00%
0/98
0.00%
0/93
Injury, poisoning and procedural complications
Foreign body
1.0%
1/98 • Number of events 1
0.00%
0/98
0.00%
0/93

Other adverse events

Other adverse events
Measure
LY2605541 Dosing Algorithm 1
n=98 participants at risk
subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
LY2605541 Dosing Algorithm 2
n=98 participants at risk
subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Insulin Glargine
n=93 participants at risk
Subcutaneous injection of insulin Glargine every morning with dose titration based on blood glucose measures for 12 weeks
Blood and lymphatic system disorders
Anaemia
2.0%
2/98 • Number of events 2
0.00%
0/98
0.00%
0/93
Blood and lymphatic system disorders
Leukocytosis
0.00%
0/98
2.0%
2/98 • Number of events 2
0.00%
0/93
Eye disorders
Eye pain
0.00%
0/98
3.1%
3/98 • Number of events 3
0.00%
0/93
Gastrointestinal disorders
Abdominal discomfort
0.00%
0/98
0.00%
0/98
2.2%
2/93 • Number of events 2
Gastrointestinal disorders
Abdominal pain upper
1.0%
1/98 • Number of events 1
0.00%
0/98
2.2%
2/93 • Number of events 2
Gastrointestinal disorders
Constipation
1.0%
1/98 • Number of events 1
2.0%
2/98 • Number of events 2
3.2%
3/93 • Number of events 3
Gastrointestinal disorders
Diarrhoea
3.1%
3/98 • Number of events 3
3.1%
3/98 • Number of events 3
3.2%
3/93 • Number of events 3
Gastrointestinal disorders
Gastrooesophageal reflux disease
0.00%
0/98
2.0%
2/98 • Number of events 2
0.00%
0/93
Gastrointestinal disorders
Nausea
2.0%
2/98 • Number of events 2
1.0%
1/98 • Number of events 1
2.2%
2/93 • Number of events 2
Gastrointestinal disorders
Vomiting
0.00%
0/98
1.0%
1/98 • Number of events 1
2.2%
2/93 • Number of events 2
General disorders
Asthenia
2.0%
2/98 • Number of events 2
0.00%
0/98
0.00%
0/93
General disorders
Fatigue
2.0%
2/98 • Number of events 2
0.00%
0/98
1.1%
1/93 • Number of events 1
Infections and infestations
Bronchitis
1.0%
1/98 • Number of events 1
1.0%
1/98 • Number of events 1
2.2%
2/93 • Number of events 2
Infections and infestations
Influenza
3.1%
3/98 • Number of events 3
2.0%
2/98 • Number of events 2
0.00%
0/93
Infections and infestations
Nasopharyngitis
3.1%
3/98 • Number of events 3
6.1%
6/98 • Number of events 6
5.4%
5/93 • Number of events 6
Infections and infestations
Sinusitis
1.0%
1/98 • Number of events 1
0.00%
0/98
2.2%
2/93 • Number of events 2
Infections and infestations
Upper respiratory tract infection
2.0%
2/98 • Number of events 2
3.1%
3/98 • Number of events 3
3.2%
3/93 • Number of events 3
Infections and infestations
Urinary tract infection
0.00%
0/98
3.1%
3/98 • Number of events 3
0.00%
0/93
Infections and infestations
Viral infection
0.00%
0/98
2.0%
2/98 • Number of events 2
1.1%
1/93 • Number of events 1
Injury, poisoning and procedural complications
Contusion
2.0%
2/98 • Number of events 3
0.00%
0/98
0.00%
0/93
Investigations
Electrocardiogram QT prolonged
0.00%
0/98
0.00%
0/98
2.2%
2/93 • Number of events 2
Metabolism and nutrition disorders
Abnormal loss of weight
2.0%
2/98 • Number of events 2
4.1%
4/98 • Number of events 4
1.1%
1/93 • Number of events 1
Metabolism and nutrition disorders
Abnormal weight gain
0.00%
0/98
2.0%
2/98 • Number of events 3
3.2%
3/93 • Number of events 3
Metabolism and nutrition disorders
Dyslipidaemia
2.0%
2/98 • Number of events 2
1.0%
1/98 • Number of events 1
0.00%
0/93
Metabolism and nutrition disorders
Hypertriglyceridaemia
0.00%
0/98
2.0%
2/98 • Number of events 2
0.00%
0/93
Metabolism and nutrition disorders
Underweight
1.0%
1/98 • Number of events 1
4.1%
4/98 • Number of events 4
0.00%
0/93
Musculoskeletal and connective tissue disorders
Back pain
2.0%
2/98 • Number of events 2
2.0%
2/98 • Number of events 3
4.3%
4/93 • Number of events 4
Musculoskeletal and connective tissue disorders
Muscle spasms
1.0%
1/98 • Number of events 1
3.1%
3/98 • Number of events 3
0.00%
0/93
Musculoskeletal and connective tissue disorders
Pain in extremity
4.1%
4/98 • Number of events 4
1.0%
1/98 • Number of events 1
1.1%
1/93 • Number of events 1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
2.0%
2/98 • Number of events 2
0.00%
0/98
0.00%
0/93
Nervous system disorders
Dizziness
3.1%
3/98 • Number of events 3
0.00%
0/98
1.1%
1/93 • Number of events 1
Nervous system disorders
Headache
4.1%
4/98 • Number of events 4
2.0%
2/98 • Number of events 2
4.3%
4/93 • Number of events 6
Psychiatric disorders
Insomnia
2.0%
2/98 • Number of events 6
0.00%
0/98
0.00%
0/93
Respiratory, thoracic and mediastinal disorders
Cough
1.0%
1/98 • Number of events 1
1.0%
1/98 • Number of events 1
2.2%
2/93 • Number of events 2
Skin and subcutaneous tissue disorders
Rash
0.00%
0/98
0.00%
0/98
2.2%
2/93 • Number of events 2
Skin and subcutaneous tissue disorders
Urticaria
0.00%
0/98
2.0%
2/98 • Number of events 2
0.00%
0/93
Vascular disorders
Hypertension
0.00%
0/98
2.0%
2/98 • Number of events 2
0.00%
0/93

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

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

Restriction type: GT60