Trial Outcomes & Findings for Study of Insulin Lispro in Participants With Inadequately Controlled Type 2 Diabetes (NCT NCT01215955)

Last Updated: 2014-04-23

Results Overview

The change from baseline to 24 weeks in the percentage of HbA1c in plasma. The Least Squares (LS) mean was estimated from a mixed-effects model with repeated measures (MMRM) that included the independent variables: fixed effects for treatment, country, sulfonylurea/meglitinide use, visit, treatment by visit interaction with baseline HbA1c as a covariate.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1117 participants

Primary outcome timeframe

Baseline, 24 weeks

Results posted on

2014-04-23

Participant Flow

Protocol had 2 independent studies (Study A, Study B) from which data was analyzed separately and independently: Participants were randomized to 1of the 2 treatment arms (Q1D, Q3D) at the site level. Sites were assigned to a study according to an allocation plan that was pre-specified before initiation of the study.

Participant milestones

Participant milestones
Measure	Study A Q1D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Overall Study STARTED	268	263	292	294
Overall Study Received at Least 1 Dose of Study Drug	267	261	288	290
Overall Study COMPLETED	223	210	244	241
Overall Study NOT COMPLETED	45	53	48	53

Reasons for withdrawal

Reasons for withdrawal
Measure	Study A Q1D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Overall Study Adverse Event	1	4	2	3
Overall Study Death	2	0	1	3
Overall Study Entry Criteria Not Met	1	3	4	7
Overall Study Lack of Efficacy	1	2	1	0
Overall Study Lost to Follow-up	4	4	8	9
Overall Study Physician Decision	4	10	8	11
Overall Study Protocol Violation	17	13	8	8
Overall Study Sponsor Decision	1	2	0	1
Overall Study Withdrawal by Subject	14	15	13	9
Overall Study Quality Issues	0	0	3	2

Baseline Characteristics

Study of Insulin Lispro in Participants With Inadequately Controlled Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Study A Q1D n=267 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated based dose was on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Total n=1106 Participants Total of all reporting groups
Age, Continuous	57.89 years STANDARD_DEVIATION 10.25 • n=5 Participants	58.82 years STANDARD_DEVIATION 9.46 • n=7 Participants	57.71 years STANDARD_DEVIATION 9.71 • n=5 Participants	57.01 years STANDARD_DEVIATION 10.61 • n=4 Participants	57.83 years STANDARD_DEVIATION 10.03 • n=21 Participants
Sex: Female, Male Female	133 Participants n=5 Participants	138 Participants n=7 Participants	155 Participants n=5 Participants	155 Participants n=4 Participants	581 Participants n=21 Participants
Sex: Female, Male Male	134 Participants n=5 Participants	123 Participants n=7 Participants	133 Participants n=5 Participants	135 Participants n=4 Participants	525 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	100 Participants n=5 Participants	96 Participants n=7 Participants	91 Participants n=5 Participants	95 Participants n=4 Participants	382 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	150 Participants n=5 Participants	153 Participants n=7 Participants	182 Participants n=5 Participants	177 Participants n=4 Participants	662 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	17 Participants n=5 Participants	12 Participants n=7 Participants	15 Participants n=5 Participants	18 Participants n=4 Participants	62 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	22 Participants n=5 Participants	20 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	64 Participants n=21 Participants
Race (NIH/OMB) Asian	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants	2 Participants n=4 Participants	18 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race (NIH/OMB) Black or African American	20 Participants n=5 Participants	15 Participants n=7 Participants	35 Participants n=5 Participants	29 Participants n=4 Participants	99 Participants n=21 Participants
Race (NIH/OMB) White	219 Participants n=5 Participants	218 Participants n=7 Participants	228 Participants n=5 Participants	240 Participants n=4 Participants	905 Participants n=21 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants	6 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants	5 Participants n=21 Participants
Region of Enrollment Argentina	28 participants n=5 Participants	28 participants n=7 Participants	37 participants n=5 Participants	38 participants n=4 Participants	131 participants n=21 Participants
Region of Enrollment Austria	0 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants	1 participants n=4 Participants	6 participants n=21 Participants
Region of Enrollment Brazil	2 participants n=5 Participants	4 participants n=7 Participants	11 participants n=5 Participants	14 participants n=4 Participants	31 participants n=21 Participants
Region of Enrollment Canada	5 participants n=5 Participants	6 participants n=7 Participants	7 participants n=5 Participants	11 participants n=4 Participants	29 participants n=21 Participants
Region of Enrollment Croatia	3 participants n=5 Participants	3 participants n=7 Participants	4 participants n=5 Participants	5 participants n=4 Participants	15 participants n=21 Participants
Region of Enrollment Denmark	5 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	0 participants n=4 Participants	6 participants n=21 Participants
Region of Enrollment France	3 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants	3 participants n=4 Participants	7 participants n=21 Participants
Region of Enrollment Lithuania	2 participants n=5 Participants	4 participants n=7 Participants	4 participants n=5 Participants	5 participants n=4 Participants	15 participants n=21 Participants
Region of Enrollment Mexico	31 participants n=5 Participants	31 participants n=7 Participants	21 participants n=5 Participants	25 participants n=4 Participants	108 participants n=21 Participants
Region of Enrollment Poland	9 participants n=5 Participants	8 participants n=7 Participants	15 participants n=5 Participants	15 participants n=4 Participants	47 participants n=21 Participants
Region of Enrollment Puerto Rico	26 participants n=5 Participants	19 participants n=7 Participants	7 participants n=5 Participants	7 participants n=4 Participants	59 participants n=21 Participants
Region of Enrollment Romania	9 participants n=5 Participants	6 participants n=7 Participants	11 participants n=5 Participants	10 participants n=4 Participants	36 participants n=21 Participants
Region of Enrollment Russian Federation	12 participants n=5 Participants	13 participants n=7 Participants	15 participants n=5 Participants	16 participants n=4 Participants	56 participants n=21 Participants
Region of Enrollment South Africa	1 participants n=5 Participants	2 participants n=7 Participants	11 participants n=5 Participants	13 participants n=4 Participants	27 participants n=21 Participants
Region of Enrollment United States	131 participants n=5 Participants	136 participants n=7 Participants	139 participants n=5 Participants	127 participants n=4 Participants	533 participants n=21 Participants

PRIMARY outcome

Timeframe: Baseline, 24 weeks

Population: Full Analysis Set: All participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin with a baseline value for HbA1C, except participants from the excluded site.

Outcome measures

Outcome measures
Measure	Study A Q1D n=267 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Change From Baseline to 24 Week Endpoint in Glycated Hemoglobin (HbA1c)	-1.00 percentage HbA1c Standard Error 0.08	-0.96 percentage HbA1c Standard Error 0.08	-0.98 percentage HbA1c Standard Error 0.07	-0.92 percentage HbA1c Standard Error 0.07

SECONDARY outcome

Timeframe: 24-week endpoint

Percentage of participants who achieved HbA1c levels of ≤7.0% or ≤6.5%.

Outcome measures

Outcome measures
Measure	Study A Q1D n=267 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values HbA1c ≤7.0%	49.81 percentage of participants	42.53 percentage of participants	49.31 percentage of participants	42.41 percentage of participants
Percentage of Participants Achieving Glycated Hemoglobin (HbA1c) Target Values HbA1c ≤6.5%	26.22 percentage of participants	23.37 percentage of participants	25.00 percentage of participants	22.76 percentage of participants

SECONDARY outcome

Timeframe: 24-week endpoint

Population: A subset of the Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin and were ≥65 years of age, except participants from the excluded site. Last observation carried forward (LOCF) was used.

Percentage of participants ≥65 years of age achieving HbA1c target concentration of ≤7.0% or ≤6.5%.

Outcome measures

Outcome measures
Measure	Study A Q1D n=65 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=69 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=56 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=65 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration HbA1c ≤7%	58.46 percentage of participants	57.97 percentage of participants	67.86 percentage of participants	46.15 percentage of participants
Percentage of Participants ≥65 Years of Age Achieving Glycated Hemoglobin (HbA1c) Target Concentration HbA1c ≤6.5%	27.69 percentage of participants	36.23 percentage of participants	35.71 percentage of participants	21.54 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 24-weeks

Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized and received ≥1 dose of study insulin with a baseline body weight, except participants from the excluded site.

Body weight was measured twice at each indicated visit and the average of the 2 measurements was used for analyses. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction .

Outcome measures

Outcome measures
Measure	Study A Q1D n=267 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Change From Baseline to 24 Week Endpoint in Body Weight	2.15 kilograms (kg) Standard Error 0.27	2.96 kilograms (kg) Standard Error 0.28	2.47 kilograms (kg) Standard Error 0.24	1.97 kilograms (kg) Standard Error 0.24

SECONDARY outcome

Timeframe: Baseline through 24 weeks

Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin, except participants from the excluded site. Censored participants: Study A: ≤6.5% Q1D=186 and Q3D=197; Study A ≤7.0% Q1D=120 and Q3D=134; Study B: ≤6.5% Q1D=206 and Q3D=212, Study B ≤7.0% Q1D=135 and Q3D=152.

Percentage of participants is the number of participants who achieved HbA1c target values of ≤6.5% or ≤7.0% during the specified time period divided by the total number of participants who did not discontinue from the study but had not reached HbA1c target at the beginning of the specified post baseline time period (≤100 days and ≥101 days). Participants who did not experience an outcome before discontinuation or completion of the study were censored using the date of discontinuation. Participants who were lost to follow up the date of discontinuation were considered to be the date of last contact.

Outcome measures

Outcome measures
Measure	Study A Q1D n=267 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Time to Reach Glycated Hemoglobin (HbA1c) Target Values HbA1c ≤6.5% Post-Baseline ≤100 days	19.48 percentage of participants	10.73 percentage of participants	17.36 percentage of participants	14.48 percentage of participants
Time to Reach Glycated Hemoglobin (HbA1c) Target Values HbA1c ≤7.0% ≥101 days post-baseline	31.54 percentage of participants	26.90 percentage of participants	28.75 percentage of participants	24.56 percentage of participants
Time to Reach Glycated Hemoglobin (HbA1c) Target Values HbA1c ≤6.5% ≥101 days post-baseline	14.80 percentage of participants	18.00 percentage of participants	14.81 percentage of participants	16.14 percentage of participants
Time to Reach Glycated Hemoglobin (HbA1c) Target Values HbA1c ≤7.0% Post-Baseline ≤100 days	37.45 percentage of participants	33.72 percentage of participants	37.15 percentage of participants	33.10 percentage of participants

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin with baseline fasting glucose values, except participants from the excluded site.

Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.

Outcome measures

Outcome measures
Measure	Study A Q1D n=267 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=287 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Change From Baseline to 24 Week Endpoint in Fasting Glucose	0.08 millimoles/liter (mmoles/L) Standard Error 0.22	0.37 millimoles/liter (mmoles/L) Standard Error 0.23	-0.36 millimoles/liter (mmoles/L) Standard Error 0.21	0.45 millimoles/liter (mmoles/L) Standard Error 0.21

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: A subset of the Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin, who are ≥65 years of age with baseline fasting glucose values, except participants from the excluded site.

Outcome measures

Outcome measures
Measure	Study A Q1D n=65 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=69 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=55 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=65 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Change From Baseline to 24 Week Endpoint in Fasting Glucose in Participants ≥65 Years of Age	0.42 millimoles/liter (mmoles/L) Standard Error 0.44	1.01 millimoles/liter (mmoles/L) Standard Error 0.46	-0.18 millimoles/liter (mmoles/L) Standard Error 0.50	0.96 millimoles/liter (mmoles/L) Standard Error 0.46

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin with baseline 1,5-AG value, except participants from the excluded site.

Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.

Outcome measures

Outcome measures
Measure	Study A Q1D n=266 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Change From Baseline to 24 Week Endpoint in 1,5-anhydroglucitol (1,5-AG)	3.24 microgram/milliliter (mcg/mL) Standard Error 0.35	3.09 microgram/milliliter (mcg/mL) Standard Error 0.36	3.22 microgram/milliliter (mcg/mL) Standard Error 0.32	2.95 microgram/milliliter (mcg/mL) Standard Error 0.31

SECONDARY outcome

Timeframe: Baseline, 24 weeks

Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin and had values at baseline and the specified timepoint, except participants from the excluded site.

7-Point Self-Monitored Blood Glucose profiles are measures of blood glucose concentration taken 7 time a day at the morning pre-meal, morning 2-hours (HR) postprandial (PP), midday pre-meal, midday 2-hours post-meal, evening pre-meal, bedtime and 0300 hour (3 am). Each participant took measures over any 3 days and the average was calculated for each of the 7 time points. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.

Outcome measures

Outcome measures
Measure	Study A Q1D n=266 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile Bedtime (214, 200, 214, 216)	-60.61 milligrams/deciliter (mg/dL) Standard Error 4.78	-62.86 milligrams/deciliter (mg/dL) Standard Error 4.91	-54.71 milligrams/deciliter (mg/dL) Standard Error 4.10	-43.52 milligrams/deciliter (mg/dL) Standard Error 4.00
Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile 0300 hour (3 am) (203, 192, 194, 193)	-26.33 milligrams/deciliter (mg/dL) Standard Error 3.87	-23.96 milligrams/deciliter (mg/dL) Standard Error 3.98	-22.40 milligrams/deciliter (mg/dL) Standard Error 3.75	-13.39 milligrams/deciliter (mg/dL) Standard Error 3.71
Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile Morning Pre-Meal (215, 200, 214, 219)	-3.97 milligrams/deciliter (mg/dL) Standard Error 3.02	-0.65 milligrams/deciliter (mg/dL) Standard Error 3.12	-1.24 milligrams/deciliter (mg/dL) Standard Error 2.22	0.85 milligrams/deciliter (mg/dL) Standard Error 2.18
Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile Morning 2-HR PP (208, 194, 202, 201)	-41.57 milligrams/deciliter (mg/dL) Standard Error 3.74	-42.28 milligrams/deciliter (mg/dL) Standard Error 3.86	-43.80 milligrams/deciliter (mg/dL) Standard Error 2.94	-39.42 milligrams/deciliter (mg/dL) Standard Error 2.93
Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile Midday Pre-Meal (214, 199, 213, 219)	-42.37 milligrams/deciliter (mg/dL) Standard Error 3.07	-40.94 milligrams/deciliter (mg/dL) Standard Error 3.16	38.57 milligrams/deciliter (mg/dL) Standard Error 2.59	-32.35 milligrams/deciliter (mg/dL) Standard Error 2.52
Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile Midday 2-HR PP (207, 195, 201, 203)	-45.75 milligrams/deciliter (mg/dL) Standard Error 3.95	-49.23 milligrams/deciliter (mg/dL) Standard Error 4.06	-53.45 milligrams/deciliter (mg/dL) Standard Error 3.35	-50.38 milligrams/deciliter (mg/dL) Standard Error 3.33
Change From Baseline to 24 Weeks in 7-Point Self-Monitored Blood Glucose (SMBG) Profile Evening Pre-Meal (214, 200, 214, 215)	-46.75 milligrams/deciliter (mg/dL) Standard Error 3.60	-43.38 milligrams/deciliter (mg/dL) Standard Error 3.70	-41.59 milligrams/deciliter (mg/dL) Standard Error 3.27	-35.94 milligrams/deciliter (mg/dL) Standard Error 3.21

SECONDARY outcome

Timeframe: 24 weeks

Population: Full Analysis Set: all participants who completed the lead-in period (if applicable), were randomized, received ≥1 dose of study insulin and with values in the specified category, except participants from the excluded site.

Total insulin was the sum of basal insulin (glargine) that was required to manage normal daily blood fluctuations and prandial insulin that was taken at meal time. Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.

Outcome measures

Outcome measures
Measure	Study A Q1D n=267 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Daily Dose of Insulin: Total, Basal and Prandial (Bolus) Basal Insulin (223, 213, 243, 239)	65.53 international units (IU) Standard Error 1.41	66.67 international units (IU) Standard Error 1.44	61.24 international units (IU) Standard Error 1.16	62.33 international units (IU) Standard Error 1.15
Daily Dose of Insulin: Total, Basal and Prandial (Bolus) Prandial (Bolus) Insulin (226, 213, 244, 241)	47.10 international units (IU) Standard Error 2.82	53.81 international units (IU) Standard Error 2.87	43.03 international units (IU) Standard Error 2.69	48.40 international units (IU) Standard Error 2.68
Daily Dose of Insulin: Total, Basal and Prandial (Bolus) Total Insulin (227, 213, 244, 242)	110.52 international units (IU) Standard Error 3.32	119.38 international units (IU) Standard Error 3.43	103.08 international units (IU) Standard Error 3.53	109.13 international units (IU) Standard Error 3.51

SECONDARY outcome

Timeframe: 24 weeks

Total insulin was the sum of basal insulin (glargine) that was required to manage normal daily blood fluctuations and prandial insulin that was taken at meal time. Total, basal and prandial amounts were then divided by the participant's body weight in kilograms (kg). Least Squares (LS) mean calculated using mixed model repeating measure (MMRM) analysis that included baseline, treatment, country, sulfonylurea/meglitinide use, baseline glycated hemoglobin (HbA1c) strata (≤8% and \>8%), visit and treatment-by-visit interaction.

Outcome measures

Outcome measures
Measure	Study A Q1D n=267 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=261 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=288 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=290 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) Basal Insulin Dose (223, 213, 243, 239)	0.68 international units/kilogram (IU/kg) Standard Error 0.01	0.70 international units/kilogram (IU/kg) Standard Error 0.01	0.64 international units/kilogram (IU/kg) Standard Error 0.01	0.66 international units/kilogram (IU/kg) Standard Error 0.01
Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) Bolus Insulin Dose (226, 213, 244, 241)	0.48 international units/kilogram (IU/kg) Standard Error 0.02	0.55 international units/kilogram (IU/kg) Standard Error 0.03	0.44 international units/kilogram (IU/kg) Standard Error 0.02	0.47 international units/kilogram (IU/kg) Standard Error 0.02
Daily Dose of Insulin Per Kilogram of Body Weight: Total, Basal and Prandial (Bolus) Total Insulin Dose (227, 213, 244, 242)	1.12 international units/kilogram (IU/kg) Standard Error 0.03	1.22 international units/kilogram (IU/kg) Standard Error 0.03	1.09 international units/kilogram (IU/kg) Standard Error 0.03	1.14 international units/kilogram (IU/kg) Standard Error 0.03

SECONDARY outcome

Timeframe: Randomization through 24 weeks overall

Population: All randomized participants except from the excluded site.

A hypoglycemic episode was defined as any time a participant felt they were experiencing a sign or symptom that was associated with hypoglycemia, or had a blood glucose level of ≤70 milligram per deciliter \[mg/dL, ≤3.9 millimoles per liter (mmol/L)\] even if it was not associated with signs, symptoms or treatment (consistent with current American Diabetes Association 2005 guidelines).

Outcome measures

Outcome measures
Measure	Study A Q1D n=268 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=263 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=289 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=292 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
The Number of Participants With a Hypoglycemic Episode (Incidence)	231 participants	218 participants	238 participants	231 participants

SECONDARY outcome

Timeframe: Randomization through 24 weeks overall

Population: All randomized participants ≥65 years old except those from the excluded site.

A hypoglycemic episode in participants ≥ 65 years of age was defined as any time a participant felt they were experiencing a sign or symptom that was associated with hypoglycemia, or had a blood glucose level of ≤70 milligram per deciliter \[mg/dL, ≤3.9 millimoles per liter (mmol/L)\] even if it was not associated with signs, symptoms or treatment (consistent with current American Diabetes Association 2005 guidelines).

Outcome measures

Outcome measures
Measure	Study A Q1D n=66 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=69 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=56 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=65 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
The Number of Participants ≥65 Years of Age With Hypoglycemic Episodes (Incidence)	60 participants	61 participants	51 participants	53 participants

SECONDARY outcome

Timeframe: Randomization through 24 weeks overall

Population: All randomized participants except those from the excluded site.

The hypoglycemia rate per 30 days was calculated as the number of hypoglycemic episodes reported divided by the number of days at risk times 30.

Outcome measures

Outcome measures
Measure	Study A Q1D n=268 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=263 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=289 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=292 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
The Rate of Hypoglycemic Episodes	3.15 hypoglycemic episodes per 30 day period Standard Deviation 0.23	3.33 hypoglycemic episodes per 30 day period Standard Deviation 0.25	3.18 hypoglycemic episodes per 30 day period Standard Deviation 0.26	3.33 hypoglycemic episodes per 30 day period Standard Deviation 0.27

SECONDARY outcome

Timeframe: Randomization up to 24 weeks

Population: All randomized participants except those from the excluded site.

Severe hypoglycemia is defined as an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. Plasma glucose measurements may not be available during such an event, but neurological recovery attributable to the restoration of plasma glucose to normal is considered sufficient evidence that the event was induced by low plasma glucose.

Outcome measures

Outcome measures
Measure	Study A Q1D n=268 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study A Q3D n=263 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study A according to an allocation plan that was pre-specified before initiation of Study A.	Study B Q1D n=289 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose reading from the previous day (Q1D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q1D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.	Study B Q3D n=292 Participants Insulin lispro administered subcutaneously, up to 3 times daily for 24 weeks. Mealtime bolus of insulin lispro self-titrated dose was based on blood glucose readings from the past 3 days (Q3D). Glargine participant-dependent doses, administered subcutaneously once daily for 24 weeks. Participants were randomized to Q3D at the site level: sites were assigned to Study B according to an allocation plan that was pre-specified before initiation of Study B.
Percentage of Participants With Severe Hypoglycemic Episodes	1.9 percentage of participants	0.8 percentage of participants	2.4 percentage of participants	2.7 percentage of participants

Adverse Events

Study A Q1D

Serious events: 21 serious events

Other events: 136 other events

Deaths: 0 deaths

Study A Q3D

Serious events: 17 serious events

Other events: 142 other events

Deaths: 0 deaths

Study B Q1D

Serious events: 21 serious events

Other events: 130 other events

Deaths: 0 deaths

Study B Q3D

Serious events: 27 serious events

Other events: 150 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