Trial Outcomes & Findings for A Study Comparing LY900014 to Insulin Lispro (Humalog) in Children and Adolescents With Type 1 Diabetes (NCT NCT03740919)

Last Updated: 2022-01-24

Results Overview

Change from baseline in HbA1c was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

751 participants

Primary outcome timeframe

Baseline, Week 26

Results posted on

2022-01-24

Participant Flow

The study included a 4-week lead-in period using open-label insulin lispro (Humalog) followed by a 26-week double-blind treatment period (LY900014 and Insulin Lispro) and one Open-label treatment arm (LY900014 Postmeal).

The purpose of the lead-in period was to obtain blood glucose (BG) values along with basal and prandial insulin doses to assess basal and mealtime insulin dosing and to determine baseline hypoglycemia rates.

Participant milestones

Participant milestones
Measure	Insulin Lispro (Humalog) Lead-in Participants were switched to open-label insulin lispro (Humalog) administered subcutaneously (SC), using a unit for unit conversion or the dose could have been determined based on investigator's clinical judgement.	Insulin Lispro (Humalog) Participants received 100 units per milliliter (U/mL) insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.	LY900014 Participants received 100 U/mL LY900014 administered SC 0 to 2 minutes before start of the meal.	LY900014 Postmeal Participants received 100 U/mL LY900014 administered SC up to 20 minutes after the start of the meal.
Lead-in Period STARTED	751	0	0	0
Lead-in Period Received at Least One Dose of Study Drug	751	0	0	0
Lead-in Period COMPLETED	716	0	0	0
Lead-in Period NOT COMPLETED	35	0	0	0
Treatment Period STARTED	0	298	280	138
Treatment Period Received at Least One Dose of Study Drug	0	298	280	138
Treatment Period COMPLETED	0	288	266	135
Treatment Period NOT COMPLETED	0	10	14	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Insulin Lispro (Humalog) Lead-in Participants were switched to open-label insulin lispro (Humalog) administered subcutaneously (SC), using a unit for unit conversion or the dose could have been determined based on investigator's clinical judgement.	Insulin Lispro (Humalog) Participants received 100 units per milliliter (U/mL) insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.	LY900014 Participants received 100 U/mL LY900014 administered SC 0 to 2 minutes before start of the meal.	LY900014 Postmeal Participants received 100 U/mL LY900014 administered SC up to 20 minutes after the start of the meal.
Lead-in Period Lost to Follow-up	1	0	0	0
Lead-in Period Physician Decision	2	0	0	0
Lead-in Period Protocol Violation	1	0	0	0
Lead-in Period Withdrawal by Subject	10	0	0	0
Lead-in Period Due to Coronavirus Disease 2019 (COVID-19)	18	0	0	0
Lead-in Period Study Task Too Burdensome	1	0	0	0
Lead-in Period Lab Results Did Not Match Inclusion Criteria	1	0	0	0
Lead-in Period Withdrew Consent Due to Required Procedures	1	0	0	0
Treatment Period Adverse Event	0	0	2	0
Treatment Period Protocol Violation	0	1	0	0
Treatment Period Withdrawal by Subject	0	7	6	2
Treatment Period Terminated by Sponsor	0	1	0	0
Treatment Period Issue with Insulin Pump	0	1	0	0
Treatment Period Due to COVID-19 Pandemic	0	0	3	1
Treatment Period Failure of Inclusion Criteria	0	0	1	0
Treatment Period Not Completing Diary	0	0	1	0
Treatment Period Insulin Painful to Participant	0	0	1	0

Baseline Characteristics

A Study Comparing LY900014 to Insulin Lispro (Humalog) in Children and Adolescents With Type 1 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Insulin Lispro (Humalog) n=298 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.	LY900014 n=280 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.	Total n=716 Participants Total of all reporting groups
Age, Continuous	12.4 years STANDARD_DEVIATION 3.2 • n=5 Participants	12.1 years STANDARD_DEVIATION 3.4 • n=7 Participants	12.3 years STANDARD_DEVIATION 3.8 • n=5 Participants	12.3 years STANDARD_DEVIATION 3.4 • n=4 Participants
Sex: Female, Male Female	140 Participants n=5 Participants	144 Participants n=7 Participants	65 Participants n=5 Participants	349 Participants n=4 Participants
Sex: Female, Male Male	158 Participants n=5 Participants	136 Participants n=7 Participants	73 Participants n=5 Participants	367 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	6 Participants n=5 Participants	6 Participants n=7 Participants	0 Participants n=5 Participants	12 Participants n=4 Participants
Race (NIH/OMB) Asian	20 Participants n=5 Participants	13 Participants n=7 Participants	7 Participants n=5 Participants	40 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race (NIH/OMB) Black or African American	7 Participants n=5 Participants	3 Participants n=7 Participants	1 Participants n=5 Participants	11 Participants n=4 Participants
Race (NIH/OMB) White	256 Participants n=5 Participants	256 Participants n=7 Participants	126 Participants n=5 Participants	638 Participants n=4 Participants
Race (NIH/OMB) More than one race	4 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	5 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	8 Participants n=4 Participants
Region of Enrollment United States	51 Participants n=5 Participants	55 Participants n=7 Participants	25 Participants n=5 Participants	131 Participants n=4 Participants
Region of Enrollment Czechia	26 Participants n=5 Participants	23 Participants n=7 Participants	11 Participants n=5 Participants	60 Participants n=4 Participants
Region of Enrollment Japan	7 Participants n=5 Participants	3 Participants n=7 Participants	2 Participants n=5 Participants	12 Participants n=4 Participants
Region of Enrollment Ukraine	57 Participants n=5 Participants	53 Participants n=7 Participants	27 Participants n=5 Participants	137 Participants n=4 Participants
Region of Enrollment United Kingdom	3 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	10 Participants n=4 Participants
Region of Enrollment Spain	21 Participants n=5 Participants	19 Participants n=7 Participants	8 Participants n=5 Participants	48 Participants n=4 Participants
Region of Enrollment Russia	23 Participants n=5 Participants	21 Participants n=7 Participants	12 Participants n=5 Participants	56 Participants n=4 Participants
Region of Enrollment Austria	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment China	11 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	22 Participants n=4 Participants
Region of Enrollment Brazil	22 Participants n=5 Participants	20 Participants n=7 Participants	13 Participants n=5 Participants	55 Participants n=4 Participants
Region of Enrollment Poland	14 Participants n=5 Participants	13 Participants n=7 Participants	6 Participants n=5 Participants	33 Participants n=4 Participants
Region of Enrollment Denmark	0 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment Italy	15 Participants n=5 Participants	15 Participants n=7 Participants	6 Participants n=5 Participants	36 Participants n=4 Participants
Region of Enrollment Mexico	25 Participants n=5 Participants	22 Participants n=7 Participants	11 Participants n=5 Participants	58 Participants n=4 Participants
Region of Enrollment Israel	15 Participants n=5 Participants	15 Participants n=7 Participants	5 Participants n=5 Participants	35 Participants n=4 Participants
Region of Enrollment France	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants	4 Participants n=4 Participants
Region of Enrollment Germany	6 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	17 Participants n=4 Participants
HbA1c at Baseline	7.81 percentage of HbA1c STANDARD_DEVIATION 0.91 • n=5 Participants	7.81 percentage of HbA1c STANDARD_DEVIATION 0.87 • n=7 Participants	7.77 percentage of HbA1c STANDARD_DEVIATION 0.85 • n=5 Participants	7.80 percentage of HbA1c STANDARD_DEVIATION 0.88 • n=4 Participants

PRIMARY outcome

Timeframe: Baseline, Week 26

Population: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug, per protocol.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=280 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=260 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Change From Baseline in Hemoglobin A1c (HbA1c) Efficacy Estimand at Week 26	0.09 percentage of HbA1c Standard Error 0.052	0.06 percentage of HbA1c Standard Error 0.054	—

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug, per protocol.

Change from baseline in HbA1c postprandial was analyzed using (MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariates of baseline value. An unstructured covariance structure will be used to model the within-participant errors. The Efficacy estimand included data collected prior to permanent discontinuation of study drug through Week 26.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=280 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=131 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Change From Baseline in HbA1c (Postprandial) at Week 26	0.09 percentage of HbA1c Standard Error 0.052	0.07 percentage of HbA1c Standard Error 0.076	—

SECONDARY outcome

Timeframe: Baseline through Week 26

Population: All randomized participants who received at least one dose of the randomly assigned study drug with non-missing baseline value and at least one non-missing post-baseline value of the response variable.

Documented post-dose hypoglycemia \<54 milligrams per deciliter (mg/dL) and ≤ 70 mg/dL that occurred 1 and 2 hours after prandial dose.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=298 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=280 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose <54 mg/dL 1 Hour Post Dose	26.50 percentage of participants Standard Error 2.563	36.79 percentage of participants Standard Error 2.891	29.70 percentage of participants Standard Error 3.897
Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose <54 mg/dL 2 Hour Post Dose	54.04 percentage of participants Standard Error 2.896	63.61 percentage of participants Standard Error 2.883	57.88 percentage of participants Standard Error 4.216
Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose ≤70 mg/dL 1 Hour Post Dose	49.67 percentage of participants Standard Error 2.901	63.92 percentage of participants Standard Error 2.874	48.51 percentage of participants Standard Error 4.261
Percentage of Participants With Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose ≤70 mg/dL 2 Hour Post Dose	77.03 percentage of participants Standard Error 2.449	82.67 percentage of participants Standard Error 2.267	70.29 percentage of participants Standard Error 3.912

SECONDARY outcome

Timeframe: Baseline through Week 26

Documented post-dose hypoglycemia event is an event of blood glucose of \< 54 mg/dL and ≤70 mg/dL that occurred within 1 and 2 hours after the prandial dose. The rate of documented hypoglycemia was estimated by a negative binomial regression including treatment and age group as independent variable and number of episodes as dependent variables with log (exposure/365.25 days) as the offset in the model.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=298 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=280 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose < 54mg/dL 1 Hour Post Dose	1.59 Events per participant per year Standard Error 0.251	2.04 Events per participant per year Standard Error 0.262	1.38 Events per participant per year Standard Error 0.287
Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose < 54 mg/dL 2 Hour Post Dose	4.48 Events per participant per year Standard Error 0.454	5.95 Events per participant per year Standard Error 0.510	6.17 Events per participant per year Standard Error 0.816
Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose ≤70 mg/dL 1 Hour Post Dose	6.54 Events per participant per year Standard Error 1.036	8.46 Events per participant per year Standard Error 0.992	5.29 Events per participant per year Standard Error 1.145
Rate of Documented Post-dose Hypoglycemic Events Within 1 and 2 Hours After the Prandial Dose ≤70 mg/dL 2 Hour Post Dose	19.0 Events per participant per year Standard Error 1.58	23.7 Events per participant per year Standard Error 1.86	21.1 Events per participant per year Standard Error 2.31

SECONDARY outcome

Timeframe: Baseline through Week 26

Documented hypoglycemia is defined as \<54 mg/dL and ≤70 mg/dL, respectively.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=298 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=280 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Percentage of Participants With Documented Hypoglycemic Events <54 mg/dL	80.81 percentage of participants Standard Error 2.283	81.37 percentage of participants Standard Error 2.329	74.45 percentage of participants Standard Error 3.718
Percentage of Participants With Documented Hypoglycemic Events ≤70 mg/dL	93.98 percentage of participants Standard Error 1.375	92.55 percentage of participants Standard Error 1.569	87.62 percentage of participants Standard Error 2.806

SECONDARY outcome

Timeframe: Week 0 through Week 26

Documented hypoglycemia is defined as a hypoglycemic event of blood glucose of ≤70 mg/dL or \<54 mg/dL. The rate of documented hypoglycemia was estimated by negative binomial regression including treatment and age group as independent variables and number of episodes as dependent variable with log (exposure/365.25 days) as the offset in the model.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=298 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=280 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Rate of Documented Hypoglycemia Events < 54 mg/dL	16.6 events per participant per year Standard Error 1.23	16.1 events per participant per year Standard Error 1.20	17.7 events per participant per year Standard Error 1.99
Rate of Documented Hypoglycemia Events ≤70 mg/dL	78.0 events per participant per year Standard Error 4.23	75.1 events per participant per year Standard Error 4.44	76.1 events per participant per year Standard Error 6.10

SECONDARY outcome

Timeframe: Week 0 through Week 26

Severe hypoglycemia: during these episodes, participants have an altered mental status and cannot assist in their own care, may be semiconscious or unconscious, or experience coma with or without seizures, and require assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. The rate of severe hypoglycemia per 100 years was calculated as: 100 times the total number of severe hypoglycemia episodes within the period divided by total exposure (in year) for all participants within the treatment group.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=298 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=280 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Rate of Severe Hypoglycemia	2.05 Events per participant per 100 years	2.20 Events per participant per 100 years	0.00 Events per participant per 100 years

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug.

Change from baseline in insulin dose was analyzed using mixed model repeated measures (MMRM) and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, age group, and HbA1c stratum (≤8.0%, \>8.0%)), baseline value, visit and treatment-by-visit interaction. An unstructured covariance structure was used to model the within-participant errors.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=283 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=264 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=132 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Change From Baseline in Insulin Dose at Week 26 Total Daily Basal Insulin Dose	2.3 Unit per day Standard Error 0.28	2.9 Unit per day Standard Error 0.29	2.7 Unit per day Standard Error 0.40
Change From Baseline in Insulin Dose at Week 26 Total Daily Insulin Dose	5.3 Unit per day Standard Error 0.66	5.8 Unit per day Standard Error 0.69	5.0 Unit per day Standard Error 0.96

SECONDARY outcome

Timeframe: Week 26

Population: All participants who were randomly assigned to study drug and had non-missing baseline value and at least one non-missing post-baseline value of the response variable.

Percentage of participants with HbA1c \< 7.0% and \<7.5% was analyzed using a longitudinal logistic regression with repeated measurements conducted by a generalized linear mixed model including independent variables of treatment, baseline HbA1c value, visit, baseline HbA1c-by-visit interaction, and treatment-by-visit interaction. An unstructured covariance structure was used.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=298 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=280 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Percentage of Participants With HbA1c < 7.0% and <7.5% HbA1c <7%	20.00 percentage of participants	21.92 percentage of participants	19.08 percentage of participants
Percentage of Participants With HbA1c < 7.0% and <7.5% HbA1c < 7.5%	40.00 percentage of participants	37.31 percentage of participants	32.82 percentage of participants

SECONDARY outcome

Timeframe: Baseline, Week 26

Population: All participants randomly assigned to study drug with baseline and at least one postbaseline measurement available while on study drug.

Change from baseline in 7-point SMBG values were analyzed using MMRM and includes fixed class effects of treatment, strata (pooled country, type of basal insulin, and age group, and HbA1c stratum (≤8.0%, \>8.0%)) baseline value, visit, and treatment-by-visit interaction. An unstructured covariance structure was used to model the within-participant errors.

Outcome measures

Outcome measures
Measure	Insulin Lispro (Humalog) n=298 Participants Participants received 100 U/mL insulin lispro (Humalog) administered SC, 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets	LY900014 n=280 Participants Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 Participants Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 Morning Premeal - Fasting	1.0 mg/dL Standard Error 2.78	-3.4 mg/dL Standard Error 2.88	-5.9 mg/dL Standard Error 4.11
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 Morning 1 hour Postmeal	-3.2 mg/dL Standard Error 2.92	-17.9 mg/dL Standard Error 3.06	-9.8 mg/dL Standard Error 4.39
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 Midday Premeal	-3.1 mg/dL Standard Error 3.06	2.5 mg/dL Standard Error 3.17	-6.0 mg/dL Standard Error 4.52
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 Midday 1 hour Postmeal	0.9 mg/dL Standard Error 2.99	-5.2 mg/dL Standard Error 3.14	-1.5 mg/dL Standard Error 4.43
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 Evening Premeal	1.0 mg/dL Standard Error 3.18	4.6 mg/dL Standard Error 3.29	0.3 mg/dL Standard Error 4.69
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 Evening 1 hour Postmeal	6.9 mg/dL Standard Error 3.22	-6.2 mg/dL Standard Error 3.39	-3.9 mg/dL Standard Error 4.79
Change From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values at Week 26 Bedtime	-1.9 mg/dL Standard Error 3.03	-2.3 mg/dL Standard Error 3.14	-2.7 mg/dL Standard Error 4.53

Adverse Events

Humalog Lead-in

Serious events: 2 serious events

Other events: 39 other events

Deaths: 0 deaths

Humalog

Serious events: 12 serious events

Other events: 60 other events

Deaths: 0 deaths

LY900014

Serious events: 6 serious events

Other events: 67 other events

Deaths: 0 deaths

LY900014 Postmeal

Serious events: 2 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Humalog Lead-in n=751 participants at risk Participants received open-label insulin lispro (Humalog) administered subcutaneously (SC), using a unit for unit conversion or the dose was determined based on the investigator's clinical judgement.	Humalog n=298 participants at risk Participants received 100 U/mL insulin lispro (Humalog) administered subcutaneously (SC), 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.	LY900014 n=280 participants at risk Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 participants at risk Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Gastrointestinal disorders Vomiting	0.13% 1/751 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	3.0% 9/298 • Number of events 11 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	3.2% 9/280 • Number of events 10 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	2.2% 3/138 • Number of events 3 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
General disorders Injection site reaction	0.13% 1/751 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/298 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	3.9% 11/280 • Number of events 14 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	1.4% 2/138 • Number of events 2 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	2.8% 21/751 • Number of events 21 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	7.7% 23/298 • Number of events 30 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	10.0% 28/280 • Number of events 37 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	5.1% 7/138 • Number of events 9 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Rhinitis	0.93% 7/751 • Number of events 7 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	3.4% 10/298 • Number of events 10 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	2.1% 6/280 • Number of events 6 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	2.9% 4/138 • Number of events 5 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.40% 3/751 • Number of events 3 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	5.4% 16/298 • Number of events 18 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	5.4% 15/280 • Number of events 17 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	1.4% 2/138 • Number of events 3 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	0.80% 6/751 • Number of events 6 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	4.4% 13/298 • Number of events 21 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	4.6% 13/280 • Number of events 22 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	3.6% 5/138 • Number of events 5 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-595-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Humalog Lead-in n=751 participants at risk Participants received open-label insulin lispro (Humalog) administered subcutaneously (SC), using a unit for unit conversion or the dose was determined based on the investigator's clinical judgement.	Humalog n=298 participants at risk Participants received 100 U/mL insulin lispro (Humalog) administered subcutaneously (SC), 0 to 2 minutes before each meal with once or twice daily basal insulin. Preprandial insulin doses were individualized and titrated according to protocol-defined targets.	LY900014 n=280 participants at risk Participants received 100 U/mL LY900014 administered SC, 0 to 2 minutes before start of the meal.	LY900014 Postmeal n=138 participants at risk Participants received 100 U/mL LY900014 administered SC, up to 20 minutes after the start of the meal.
Congenital, familial and genetic disorders Macroglossia	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/298 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.36% 1/280 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Gastrointestinal disorders Gastritis	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Immune system disorders Anaphylactic reaction	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Complicated appendicitis	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/298 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.72% 1/138 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Gastroenteritis	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Pilonidal cyst	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Infections and infestations Upper respiratory tract infection	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/298 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.36% 1/280 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Reactive gastropathy	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Skin laceration	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Spinal fracture	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/298 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.71% 2/280 • Number of events 2 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.72% 1/138 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hypoglycaemia	0.13% 1/751 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.67% 2/298 • Number of events 2 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	1.1% 3/280 • Number of events 3 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Nervous system disorders Headache	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/298 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.36% 1/280 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Nervous system disorders Hypoglycaemic coma	0.00% 0/751 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.34% 1/298 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.
Psychiatric disorders Mental disorder	0.13% 1/751 • Number of events 1 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/298 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/280 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.	0.00% 0/138 • From Lead-in to Safety Follow-up (up to 32 Weeks) All randomized participants who received at least one dose of study drug.