Trial Outcomes & Findings for A Study of LY2605541 in Participants With Type 2 Diabetes Mellitus (NCT NCT01582451)

Last Updated: 2018-04-20

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, baseline low-density lipoprotein cholesterol \[LDL-C, \<100 milligrams per deciliter (mg/dL) and ≥100 mg/dL\], and sulfonylurea (SU) or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

466 participants

Primary outcome timeframe

Baseline, 26 weeks

Results posted on

2018-04-20

Participant Flow

Participant milestones

Participant milestones
Measure	LY2605541 LY2605541 was administered by subcutaneous (SQ) injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on fasting blood glucose (FBG).	Insulin Glargine Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Overall Study STARTED	307	159
Overall Study Received at Least 1 Dose of Study Drug	305	159
Overall Study COMPLETED	275	139
Overall Study NOT COMPLETED	32	20

Reasons for withdrawal

Reasons for withdrawal
Measure	LY2605541 LY2605541 was administered by subcutaneous (SQ) injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on fasting blood glucose (FBG).	Insulin Glargine Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Overall Study Adverse Event	1	3
Overall Study Death	3	3
Overall Study Lost to Follow-up	0	2
Overall Study Protocol Violation	11	3
Overall Study Withdrawal by Subject	13	9
Overall Study Physician Decision	3	0
Overall Study Sponsor Decision	1	0

Baseline Characteristics

A Study of LY2605541 in Participants With Type 2 Diabetes Mellitus

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	LY2605541 n=307 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=159 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Total n=466 Participants Total of all reporting groups
Age, Continuous	61.84 years STANDARD_DEVIATION 8.52 • n=5 Participants	60.38 years STANDARD_DEVIATION 10.10 • n=7 Participants	61.34 years STANDARD_DEVIATION 9.11 • n=5 Participants
Sex: Female, Male Female	132 Participants n=5 Participants	66 Participants n=7 Participants	198 Participants n=5 Participants
Sex: Female, Male Male	175 Participants n=5 Participants	93 Participants n=7 Participants	268 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	57 Participants n=5 Participants	25 Participants n=7 Participants	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	215 Participants n=5 Participants	115 Participants n=7 Participants	330 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	35 Participants n=5 Participants	19 Participants n=7 Participants	54 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Black or African American	17 Participants n=5 Participants	9 Participants n=7 Participants	26 Participants n=5 Participants
Race (NIH/OMB) White	280 Participants n=5 Participants	148 Participants n=7 Participants	428 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	170 Participants n=5 Participants	85 Participants n=7 Participants	255 Participants n=5 Participants
Region of Enrollment Czechia	20 Participants n=5 Participants	10 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Greece	16 Participants n=5 Participants	5 Participants n=7 Participants	21 Participants n=5 Participants
Region of Enrollment Spain	27 Participants n=5 Participants	12 Participants n=7 Participants	39 Participants n=5 Participants
Region of Enrollment Romania	16 Participants n=5 Participants	14 Participants n=7 Participants	30 Participants n=5 Participants
Region of Enrollment Israel	16 Participants n=5 Participants	8 Participants n=7 Participants	24 Participants n=5 Participants
Region of Enrollment Russia	17 Participants n=5 Participants	9 Participants n=7 Participants	26 Participants n=5 Participants
Region of Enrollment Germany	25 Participants n=5 Participants	16 Participants n=7 Participants	41 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 26 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

Outcome measures

Outcome measures
Measure	LY2605541 n=302 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Change From Baseline to 26-week Endpoint in Hemoglobin A1c (HbA1c)	-0.82 percentage of HbA1c Standard Error 0.04	-0.29 percentage of HbA1c Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline, 52 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

LS means were calculated using MMRM adjusting for stratification factors (country, baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline HbA1c.

Outcome measures

Outcome measures
Measure	LY2605541 n=302 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Change From Baseline to 52 Weeks in HbA1c	-0.67 percentage of HbA1c Standard Error 0.05	-0.22 percentage of HbA1c Standard Error 0.06

SECONDARY outcome

Timeframe: Baseline through 26 weeks and Baseline through 52 weeks

Population: 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 \[mmol/L\]). A nocturnal hypoglycemic event occurred between bedtime and waking. Group mean rates of total and nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models (number of episodes = treatment + baseline hypoglycemia rate + baseline SU or meglitinide use, 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

Outcome measures
Measure	LY2605541 n=304 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=159 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Rate of Total and Nocturnal Hypoglycemia Events (Adjusted by 30 Days) Nocturnal hypoglycemia, 0-52 weeks	0.35 events/participant/30 days Standard Error 0.06	0.88 events/participant/30 days Standard Error 0.14
Rate of Total and Nocturnal Hypoglycemia Events (Adjusted by 30 Days) Total hypoglycemia, 0-26 weeks	1.55 events/participant/30 days Standard Error 0.13	1.98 events/participant/30 days Standard Error 0.19
Rate of Total and Nocturnal Hypoglycemia Events (Adjusted by 30 Days) Total hypoglycemia, 0-52 weeks	1.24 events/participant/30 days Standard Error 0.10	1.62 events/participant/30 days Standard Error 0.15
Rate of Total and Nocturnal Hypoglycemia Events (Adjusted by 30 Days) Nocturnal hypoglycemia, 0-26 weeks	0.43 events/participant/30 days Standard Error 0.06	1.04 events/participant/30 days Standard Error 0.15

SECONDARY outcome

Timeframe: Baseline through 26 weeks and Baseline through 52 weeks

Population: 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). A nocturnal hypoglycemic event occurred between bedtime and waking. 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

Outcome measures
Measure	LY2605541 n=304 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=159 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Percentage of Participants That Have Total and Nocturnal Hypoglycemic Events Total hypoglycemia, 0-26 weeks	76.3 percentage of participants	80.5 percentage of participants
Percentage of Participants That Have Total and Nocturnal Hypoglycemic Events Total hypoglycemia, 0-52 weeks	80.3 percentage of participants	83.0 percentage of participants
Percentage of Participants That Have Total and Nocturnal Hypoglycemic Events Nocturnal hypoglycemia, 0-26 weeks	46.1 percentage of participants	62.3 percentage of participants
Percentage of Participants That Have Total and Nocturnal Hypoglycemic Events Nocturnal hypoglycemia, 0-52 weeks	50.3 percentage of participants	67.3 percentage of participants

SECONDARY outcome

Timeframe: 26 and 52 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data. Missing endpoints were imputed with by applying the last observation carried forward (LOCF) method to the 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

Outcome measures
Measure	LY2605541 n=302 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Percentage of Participants With HbA1c Equal to or Less Than (≤) 6.5% and Less Than (<) 7.0% HbA1c ≤6.5%, 26 weeks	50.3 percentage of participants	28.7 percentage of participants
Percentage of Participants With HbA1c Equal to or Less Than (≤) 6.5% and Less Than (<) 7.0% HbA1c ≤6.5%, 52 weeks	43.4 percentage of participants	28.0 percentage of participants
Percentage of Participants With HbA1c Equal to or Less Than (≤) 6.5% and Less Than (<) 7.0% HbA1c <7.0%, 26 weeks	72.5 percentage of participants	52.2 percentage of participants
Percentage of Participants With HbA1c Equal to or Less Than (≤) 6.5% and Less Than (<) 7.0% HbA1c <7.0%, 52 weeks	63.9 percentage of participants	45.9 percentage of participants

SECONDARY outcome

Timeframe: 26 and 52 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data. Missing endpoints were imputed with by applying the LOCF method to the 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. 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

Outcome measures
Measure	LY2605541 n=302 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia 26 weeks	40.1 percentage of participants	18.5 percentage of participants
Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia 52 weeks	34.8 percentage of participants	10.2 percentage of participants

SECONDARY outcome

Timeframe: 26 and 52 weeks

Population: 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 (country, baseline HbA1c \[≤8.0% and \>8.0%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline FSG.

Outcome measures

Outcome measures
Measure	LY2605541 n=302 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Fasting Serum Glucose (FSG) (by Laboratory) 26 weeks	103.80 milligrams per deciliter (mg/dL) Standard Error 1.88	119.50 milligrams per deciliter (mg/dL) Standard Error 2.64
Fasting Serum Glucose (FSG) (by Laboratory) 52 weeks	107.61 milligrams per deciliter (mg/dL) Standard Error 1.94	115.74 milligrams per deciliter (mg/dL) Standard Error 2.72

SECONDARY outcome

Timeframe: 26 and 52 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable FBG data at both baseline and post-baseline.

Outcome measures

Outcome measures
Measure	LY2605541 n=303 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=158 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Fasting Blood Glucose (FBG) (by Self Monitoring) 26 weeks	106.32 milligrams per deciliter (mg/dL) Standard Error 1.08	104.50 milligrams per deciliter (mg/dL) Standard Error 1.51
Fasting Blood Glucose (FBG) (by Self Monitoring) 52 weeks	110.61 milligrams per deciliter (mg/dL) Standard Error 1.19	107.46 milligrams per deciliter (mg/dL) Standard Error 1.68

SECONDARY outcome

Timeframe: 26 and 52 weeks

Population: 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 (country, baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), treatment, visit, treatment-by-visit interaction, and baseline FBG intra-participant variability.

Outcome measures

Outcome measures
Measure	LY2605541 n=302 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=158 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Intra-participant Variability in Fasting Blood Glucose (FBG) 26 weeks	13.70 mg/dL Standard Error 0.57	17.90 mg/dL Standard Error 0.80
Intra-participant Variability in Fasting Blood Glucose (FBG) 52 weeks	14.18 mg/dL Standard Error 0.65	17.38 mg/dL Standard Error 0.91

SECONDARY outcome

Timeframe: 26 and 52 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable SMBG data at both baseline and post-baseline.

SMBG measurements were taken at 6 time points (pre-morning meal \[fasting\], pre-midday meal, pre-evening meal, bedtime, approximately 0300 hours, and pre-morning meal \[fasting\] on the next day) and were performed on 2 non-consecutive days in the week prior to next office visit. 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 SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline BG values.

Outcome measures

Outcome measures
Measure	LY2605541 n=288 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=148 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
6-point Self-monitored Blood Glucose (SMBG) Pre-morning meal, 26 weeks	107.93 mg/dL Standard Error 1.30	104.11 mg/dL Standard Error 1.83
6-point Self-monitored Blood Glucose (SMBG) Pre-midday meal, 26 weeks	120.87 mg/dL Standard Error 2.20	132.56 mg/dL Standard Error 3.11
6-point Self-monitored Blood Glucose (SMBG) Pre-evening meal, 26 weeks	125.87 mg/dL Standard Error 2.18	141.45 mg/dL Standard Error 3.08
6-point Self-monitored Blood Glucose (SMBG) Bedtime, 26 weeks	146.54 mg/dL Standard Error 2.61	161.48 mg/dL Standard Error 3.69
6-point Self-monitored Blood Glucose (SMBG) 0300 hours, 26 weeks	118.43 mg/dL Standard Error 2.04	120.42 mg/dL Standard Error 2.87
6-point Self-monitored Blood Glucose (SMBG) Pre-morning meal next day, 26 weeks	106.28 mg/dL Standard Error 1.36	102.79 mg/dL Standard Error 1.90
6-point Self-monitored Blood Glucose (SMBG) Pre-morning meal, 52 weeks	110.84 mg/dL Standard Error 1.39	108.22 mg/dL Standard Error 1.94
6-point Self-monitored Blood Glucose (SMBG) Pre-midday meal, 52 weeks	121.34 mg/dL Standard Error 2.17	130.55 mg/dL Standard Error 3.06
6-point Self-monitored Blood Glucose (SMBG) Pre-evening meal, 52 weeks	128.53 mg/dL Standard Error 2.00	141.31 mg/dL Standard Error 2.82
6-point Self-monitored Blood Glucose (SMBG) Bedtime, 52 weeks	146.92 mg/dL Standard Error 2.37	161.83 mg/dL Standard Error 3.34
6-point Self-monitored Blood Glucose (SMBG) 0300 hours, 52 weeks	122.23 mg/dL Standard Error 1.96	121.07 mg/dL Standard Error 2.76
6-point Self-monitored Blood Glucose (SMBG) Pre-morning meal next day, 52 weeks	110.38 mg/dL Standard Error 1.41	106.68 mg/dL Standard Error 1.97

SECONDARY outcome

Timeframe: 26 and 52 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable HbA1c data at both baseline and post-baseline.

Outcome measures

Outcome measures
Measure	LY2605541 n=302 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
HbA1c 26 weeks	6.60 percentage of HbA1c Standard Error 0.04	7.13 percentage of HbA1c Standard Error 0.06
HbA1c 52 weeks	6.75 percentage of HbA1c Standard Error 0.05	7.20 percentage of HbA1c Standard Error 0.06

SECONDARY outcome

Timeframe: 26 and 52 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable insulin dose data.

Daily basal insulin dose is presented. LS means were calculated using MMRM adjusting for the stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use), treatment, visit, treatment-by-visit interaction, and baseline insulin dose.

Outcome measures

Outcome measures
Measure	LY2605541 n=304 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=159 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Insulin Dose Per Kilogram of Body Weight 26 weeks	0.57 units per kilogram per day (U/kg/day) Standard Error 0.01	0.49 units per kilogram per day (U/kg/day) Standard Error 0.01
Insulin Dose Per Kilogram of Body Weight 52 weeks	0.58 units per kilogram per day (U/kg/day) Standard Error 0.01	0.49 units per kilogram per day (U/kg/day) Standard Error 0.02

SECONDARY outcome

Timeframe: Baseline through 26 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable insulin dose data at both baseline and post-baseline.

The number of dose adjustments required to reach a steady dose is presented. LS means were calculated from negative binomial regression models, where the number of dose adjustments = treatment + stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], baseline LDL-C \[\<100 mg/dL and ≥100 mg/dL\], and SU or meglitinide use).

Outcome measures

Outcome measures
Measure	LY2605541 n=304 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=159 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Number of Insulin Dose Adjustments to Steady-state	4.06 number of dose adjustments Standard Error 0.16	2.75 number of dose adjustments Standard Error 0.20

SECONDARY outcome

Timeframe: 26 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable EuroQol-5D data at both baseline and post-baseline. Missing endpoints were imputed by applying the LOCF method to the post-baseline data.

The EuroQol-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 3-level scale of 1-3 (no problem, some problems, and extreme problems). These combinations of attributes are converted into a weighted health-state Index Score according to the United States population-based algorithm. Scores range from -0.11 to 1.0, where a score of 1.0 indicates perfect health. LS means were calculated using an analysis of covariance (ANCOVA) model adjusting for treatment, stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], and SU or meglitinide use), and baseline EuroQol-5D score.

Outcome measures

Outcome measures
Measure	LY2605541 n=290 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=146 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
European Quality of Life - 5 Dimension (EuroQol-5D) Score	0.87 units on a scale Standard Error 0.01	0.88 units on a scale Standard Error 0.01

SECONDARY outcome

Timeframe: 26 weeks

Population: 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 by applying the LOCF method to the post-baseline data.

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 a higher score indicate better treatment satisfaction. LS means were calculated using ANCOVA with treatment and stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], and SU or meglitinide use) as fixed effects and baseline value of the ITSQ score as a covariate.

Outcome measures

Outcome measures
Measure	LY2605541 n=291 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=148 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Insulin Treatment Satisfaction Questionnaire (ITSQ) Score	85.69 units on a scale Standard Error 0.63	84.43 units on a scale Standard Error 0.89

SECONDARY outcome

Timeframe: 26 weeks

Population: Participants who were randomized, had at least 1 dose of study medication, and had evaluable LBSS data at both baseline and post-baseline. Missing endpoints were imputed by applying the LOCF method to the post-baseline data.

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 ANCOVA with treatment and stratification factors (country, baseline HbA1c \[≤8.5% and \>8.5%\], and SU or meglitinide use) as fixed effects and baseline value of the LBSS score as a covariate.

Outcome measures

Outcome measures
Measure	LY2605541 n=292 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=148 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Adult Low Blood Sugar Survey (LBSS) Score	16.57 units on a scale Standard Error 0.77	15.63 units on a scale Standard Error 1.08

SECONDARY outcome

Timeframe: Baseline, 26 weeks, 52 weeks

Population: 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 (country, baseline HbA1c \[≤8.5% and \>8.5%\], LDL-C \[\<100 mg/dL and ≥100 mg/dL, except for the LDL-C outcome variable\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline body weight.

Outcome measures

Outcome measures
Measure	LY2605541 n=303 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Change From Baseline in Body Weight 26 weeks	0.50 kilograms (kg) Standard Error 0.17	0.94 kilograms (kg) Standard Error 0.24
Change From Baseline in Body Weight 52 weeks	0.69 kilograms (kg) Standard Error 0.23	1.32 kilograms (kg) Standard Error 0.32

SECONDARY outcome

Timeframe: Baseline, 26 weeks, 52 weeks

Population: 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 (country, baseline HbA1c \[≤8.5% and \>8.5%\], LDL-C \[\<100 mg/dL and ≥100 mg/dL, except for the LDL-C outcome variable\], and SU or meglitinide use), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable.

Outcome measures

Outcome measures
Measure	LY2605541 n=302 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Change From Baseline in Lipid Profile Cholesterol, 26 weeks	2.24 mg/dL Standard Error 1.60	3.70 mg/dL Standard Error 2.25
Change From Baseline in Lipid Profile Cholesterol, 52 weeks	-1.35 mg/dL Standard Error 1.63	2.78 mg/dL Standard Error 2.29
Change From Baseline in Lipid Profile HDL-C, 26 weeks	-1.74 mg/dL Standard Error 0.37	-0.06 mg/dL Standard Error 0.52
Change From Baseline in Lipid Profile HDL-C, 52 weeks	-3.52 mg/dL Standard Error 0.37	-2.01 mg/dL Standard Error 0.51
Change From Baseline in Lipid Profile LDL-C, 26 weeks	-0.05 mg/dL Standard Error 1.43	4.54 mg/dL Standard Error 2.00
Change From Baseline in Lipid Profile LDL-C, 52 weeks	-3.38 mg/dL Standard Error 1.45	3.41 mg/dL Standard Error 2.03
Change From Baseline in Lipid Profile Triglycerides, 26 weeks	22.53 mg/dL Standard Error 3.73	-2.90 mg/dL Standard Error 5.23
Change From Baseline in Lipid Profile Triglycerides, 52 week	27.39 mg/dL Standard Error 4.00	12.02 mg/dL Standard Error 5.59

SECONDARY outcome

Timeframe: Baseline through 52 weeks

Population: 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

Outcome measures
Measure	LY2605541 n=301 Participants LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=157 Participants Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Number of Participants With Change in Anti-LY2605541 Antibodies	70 participants	30 participants

Adverse Events

LY2605541

Serious events: 36 serious events

Other events: 223 other events

Deaths: 0 deaths

Insulin Glargine

Serious events: 22 serious events

Other events: 104 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

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

Measure	LY2605541 n=305 participants at risk LY2605541 was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.	Insulin Glargine n=159 participants at risk Insulin glargine was administered by SQ injection once daily at bedtime for up to 52 weeks. Initial dose based on dose of prestudy basal insulin and adjusted based on FBG.
Blood and lymphatic system disorders Anaemia	0.98% 3/305 • Number of events 3 Includes events from participants who were randomized and had at least 1 dose of study medication.	3.1% 5/159 • Number of events 5 Includes events from participants who were randomized and had at least 1 dose of study medication.
Gastrointestinal disorders Diarrhoea	6.2% 19/305 • Number of events 21 Includes events from participants who were randomized and had at least 1 dose of study medication.	3.8% 6/159 • Number of events 6 Includes events from participants who were randomized and had at least 1 dose of study medication.
Gastrointestinal disorders Nausea	3.9% 12/305 • Number of events 13 Includes events from participants who were randomized and had at least 1 dose of study medication.	2.5% 4/159 • Number of events 7 Includes events from participants who were randomized and had at least 1 dose of study medication.
Infections and infestations Bronchitis	4.6% 14/305 • Number of events 14 Includes events from participants who were randomized and had at least 1 dose of study medication.	3.1% 5/159 • Number of events 5 Includes events from participants who were randomized and had at least 1 dose of study medication.
Infections and infestations Influenza	4.3% 13/305 • Number of events 14 Includes events from participants who were randomized and had at least 1 dose of study medication.	6.9% 11/159 • Number of events 13 Includes events from participants who were randomized and had at least 1 dose of study medication.
Infections and infestations Nasopharyngitis	16.4% 50/305 • Number of events 63 Includes events from participants who were randomized and had at least 1 dose of study medication.	17.0% 27/159 • Number of events 33 Includes events from participants who were randomized and had at least 1 dose of study medication.
Infections and infestations Sinusitis	5.9% 18/305 • Number of events 19 Includes events from participants who were randomized and had at least 1 dose of study medication.	5.7% 9/159 • Number of events 9 Includes events from participants who were randomized and had at least 1 dose of study medication.
Infections and infestations Upper respiratory tract infection	5.2% 16/305 • Number of events 18 Includes events from participants who were randomized and had at least 1 dose of study medication.	5.0% 8/159 • Number of events 11 Includes events from participants who were randomized and had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Arthralgia	4.9% 15/305 • Number of events 18 Includes events from participants who were randomized and had at least 1 dose of study medication.	4.4% 7/159 • Number of events 7 Includes events from participants who were randomized and had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Back pain	6.9% 21/305 • Number of events 22 Includes events from participants who were randomized and had at least 1 dose of study medication.	5.7% 9/159 • Number of events 10 Includes events from participants who were randomized and had at least 1 dose of study medication.
Musculoskeletal and connective tissue disorders Pain in extremity	2.3% 7/305 • Number of events 7 Includes events from participants who were randomized and had at least 1 dose of study medication.	5.7% 9/159 • Number of events 9 Includes events from participants who were randomized and had at least 1 dose of study medication.
Nervous system disorders Dizziness	2.3% 7/305 • Number of events 8 Includes events from participants who were randomized and had at least 1 dose of study medication.	3.1% 5/159 • Number of events 6 Includes events from participants who were randomized and had at least 1 dose of study medication.
Nervous system disorders Headache	4.9% 15/305 • Number of events 21 Includes events from participants who were randomized and had at least 1 dose of study medication.	7.5% 12/159 • Number of events 27 Includes events from participants who were randomized and had at least 1 dose of study medication.
Psychiatric disorders Anxiety	0.66% 2/305 • Number of events 5 Includes events from participants who were randomized and had at least 1 dose of study medication.	3.1% 5/159 • Number of events 5 Includes events from participants who were randomized and had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Cough	5.2% 16/305 • Number of events 17 Includes events from participants who were randomized and had at least 1 dose of study medication.	5.7% 9/159 • Number of events 9 Includes events from participants who were randomized and had at least 1 dose of study medication.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	2.0% 6/305 • Number of events 6 Includes events from participants who were randomized and had at least 1 dose of study medication.	4.4% 7/159 • Number of events 8 Includes events from participants who were randomized and had at least 1 dose of study medication.
Skin and subcutaneous tissue disorders Rash	3.3% 10/305 • Number of events 11 Includes events from participants who were randomized and had at least 1 dose of study medication.	0.63% 1/159 • Number of events 1 Includes events from participants who were randomized and had at least 1 dose of study medication.
Vascular disorders Hypertension	2.6% 8/305 • Number of events 8 Includes events from participants who were randomized and had at least 1 dose of study medication.	3.1% 5/159 • Number of events 5 Includes events from participants who were randomized and had at least 1 dose of study medication.