A Study for Patients With Type 2 Diabetes

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01027871
• Collaborator: (none)
• Enrollment: 289
• Locations: 25
• Arms: 3
• Duration (Months): 12
• Patients Per Site: 11.6
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

Comparison of fasting blood glucose levels in patients with Type 2 diabetes after 12 weeks of treatment with a new basal insulin analog or with insulin glargine.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 2	Drug: LY2605541; Drug: insulin glargine	Phase 2

Detailed Description

Patients in this study will continue to use their stable prestudy dose of metformin and/or a sulfonylurea. Prestudy therapy also includes once daily insulin glargine or neutral protamine Hagedorn (NPH) insulin. The 12-week active treatment phase will be followed by a 4-week follow-up period, during which patients will return to the basal insulin recommended by the investigator.

Study Design

• Study Type: Interventional
• Actual Enrollment: 289 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Study of LY2605541 Compared With Insulin Glargine in the Treatment of Type 2 Diabetes Mellitus
• Study Start Date: Jan 1, 2010
• Actual Primary Completion Date: Dec 1, 2010
• Actual Study Completion Date: Jan 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LY2605541 Dosing Algorithm 1 Participants took both LY2605541 and their pre-study insulin for first several days	Drug: LY2605541; subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Experimental: LY2605541 Dosing Algorithm 2 Participants took only LY2605541 with first dose doubled	Drug: LY2605541; subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Active Comparator: Insulin glargine	Drug: insulin glargine; subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks

Outcome Measures

Primary Outcome Measures

1. Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles [Week 12]

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

Secondary Outcome Measures

1. Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint [Baseline, Week 12]

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

2. Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Endpoint [Baseline, Week 12]

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

3. Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint [Week 12]

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

4. Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment [Week 12]

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

5. 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint [Week 12]

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

6. Daily Basal Insulin Dose at Week 2 and Week 12 [Week 2 and Week 12]

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

7. Percentage of Participants With Hypoglycemia From Baseline Through Week 12 [Baseline through Week 12]

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

8. Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 [Baseline through Week 12]

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

9. Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16 [Week 12 and Week 16]

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

10. Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 [Baseline and Week12]

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

11. Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 12 Endpoint [Week 12]

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

12. Change From Baseline in Fasting Blood Glucose (FBG) at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms [Baseline, Week 12]

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

13. Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms [Baseline, Week 12]

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

14. Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms [Week 12]

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

15. Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms [Week 12]

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

16. 8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms [Week 12]

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

17. Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms [Week 2 and Week 12]

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

18. Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms [Baseline through Week 12]

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

19. Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms [Baseline through Week 12]

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

20. Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms [Baseline and Week 12]

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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Type 2 diabetes mellitus (T2DM) for at least 1 year

• At least 18 years of age

• Using metformin and/or sulfonylurea(s) with once daily glargine or NPH for at least 3 months prior to the study. Prestudy dose requirements: insulin dose maximum 1.0 unit/kilogram/day (U/kg/day). Oral antihyperglycemic medications (OAMs): Metformin dose at least 1500 milligram/day (mg/day) and/or sulfonylurea dose at least half the maximum daily dose specified in the local package insert. OAM doses stable for 6 weeks prior to the study.

• Hemoglobin A1c (HbA1c) less than or equal to 10.5% before randomization

• Body Mass Index (BMI) 19 to 45 kilogram/square meter (kg/m²)

• Capable and willing to prepare and inject insulin with a syringe while continuing to use the prestudy OAMs, monitor own blood glucose; complete the study diary; be receptive to diabetes education; comply with study visits and receive telephone calls between visits

• Women of childbearing potential must test negative for pregnancy before receiving treatment and agree to use reliable birth control until completing the follow-up visit

Exclusion Criteria:

• Long-term use of short- or rapid-acting or premixed insulin within the 6 months before the study. Short-term insulin therapy or occasional use are permitted

• Use of any glucose-lowering medications not allowed by the inclusion criteria in the 3 months before entry into the study

• Use of prescription or over-the-counter medications to promote weight loss within 3 months before entry into the study

• Current participation in a weight loss program, or plans to do so during the study

• Treatment with any antibody-based therapy within 6 months prior to the study

• Use of chronic (>14 consecutive days) systemic glucocorticoid therapy currently or within 4 weeks prior to the study

• More than 1 episode of severe hypoglycemia within 6 months prior to the study, or currently diagnosed with hypoglycemia unawareness

• 2 or more emergency room visits or hospitalizations due to poor glucose control in the 6 months preceding the study

• Liver disease

• History of renal transplantation, current renal dialysis, or creatinine >2.0 milligram/deciliter (mg/dL) (177 micromole/Liter [μmol]/L)

• Cardiac disease with a marked impact on physical functioning

• Clinically significant electrocardiogram (ECG) abnormalities at screening

• Malignancy other than basal cell or squamous cell skin cancer

• Fasting triglycerides >500 mg/dL

• Known diabetic autonomic neuropathy

• Known hypersensitivity or allergy to study insulin or its excipients

• Blood transfusion or severe blood loss within 3 months prior to entry into the study or known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the HbA1c methodology

• Irregular sleep/wake cycle

• Women who are breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Idaho Falls	Idaho	United States	83404
2	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Minneapolis	Minnesota	United States	55416
3	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dallas	Texas	United States	75230
4	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Coffs Harbour	New South Wales	Australia	2450
5	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Keswick	South Australia	Australia	5035
6	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Ringwood East	Victoria	Australia	3135
7	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Fremantle	Western Australia	Australia	6160
8	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Budapest		Hungary	H-1139
9	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Gyula		Hungary	5700
10	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Veszprem		Hungary	8200
11	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Bialystok		Poland	15-950
12	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Lublin		Poland	20-044
13	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Hato Rey		Puerto Rico	00917
14	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Manati		Puerto Rico	00674
15	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	San Juan		Puerto Rico	00907
16	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Cluj-Napoca		Romania	400006
17	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Iasi		Romania	70057
18	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Targu Mures		Romania	540098
19	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Arkhangelsk		Russian Federation	163045
20	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Moscow		Russian Federation	119881
21	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Rostov-On-Don		Russian Federation	344022
22	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Saint Petersburg		Russian Federation	193257
23	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Alicante		Spain	03114
24	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Dos Hermanas		Spain	41014
25	For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.	Malaga		Spain	29010

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Study Documents (Full-Text)

None provided.

More Information

Publications

• Workgroup on Hypoglycemia, American Diabetes Association. Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care. 2005 May;28(5):1245-9. Review.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT01027871
• Other Study ID Numbers: 12149; I2R-MC-BIAC
• First Posted: Dec 9, 2009
• Last Update Posted: Jun 8, 2018
• Last Verified: May 1, 2018

• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Insulin Glargine

Study Results

Participant Flow

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

Baseline Characteristics

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algrithm 2	Total
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days	Participants took only LY2605541 with first dose doubled	Total of all reporting groups
Overall Participants	93	98	97	288
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.74 (7.94)	58.57 (9.99)	59.23 (9.28)	59.49 (9.14)
Sex: Female, Male (Count of Participants)
Female	46 49.5%	41 41.8%	48 49.5%	135 46.9%
Male	47 50.5%	57 58.2%	49 50.5%	153 53.1%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaska Native	1 1.1%	0 0%	0 0%	1 0.3%
Asian	0 0%	4 4.1%	2 2.1%	6 2.1%
Black or African American	4 4.3%	2 2%	6 6.2%	12 4.2%
Multiple	1 1.1%	0 0%	0 0%	1 0.3%
White	87 93.5%	0 0%	0 0%	87 30.2%
Region of Enrollment (Count of Participants)
United States	23 24.7%	31 31.6%	37 38.1%	91 31.6%
Hungary	5 5.4%	5 5.1%	6 6.2%	16 5.6%
Puerto Rico	12 12.9%	8 8.2%	9 9.3%	29 10.1%
Poland	0 0%	2 2%	2 2.1%	4 1.4%
Spain	13 14%	11 11.2%	12 12.4%	36 12.5%
Romania	12 12.9%	13 13.3%	12 12.4%	37 12.8%
Australia	10 10.8%	5 5.1%	6 6.2%	21 7.3%
Russia	18 19.4%	13 13.3%	12 12.4%	43 14.9%

Outcome Measures

1. Primary Outcome

Title	Fasting Blood Glucose (FBG) Level at Week 12 Endpoint as Measured by the 8-Point Self-Monitored Blood Glucose (SMBG) Profiles
Description	8-point SMBG profiles are measured at morning FBG, midday and evening pre-meal blood glucose (BG), 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. Least squares (LS) mean of the FBG is from mixed-model repeated measures (MMRM) approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-interim analysis [IA], post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline hemoglobin A1c [HbA1c] group); visit; visit and treatment interaction; random effect for participant.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	89	86	91
Least Squares Mean (Standard Error) [millimoles per Liter (mmol/L)]	6.83 (0.22)	7.15 (0.22)	6.84 (0.22)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.433
	Comments	The statistical significance level is 0.10.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 90%; -0.18 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	LY2605541 Dosing Algorithm 1 + LY2605541 Dosing Algorithm 2 Algorithm 1: Participants took both LY2605541 and their pre-study insulin for first several days Algorithm 2: Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	89	177
Least Squares Mean (Standard Error) [mmol/Liter]	-1.77 (0.26)	-1.97 (0.21)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.388
	Comments	The statistical significance level is 0.10.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.20
	Confidence Interval	(2-Sided) 90%; -0.59 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

3. Secondary Outcome

Title	Change From Baseline in Hemoglobin A1c (HbA1c) at Week 12 Endpoint
Description	HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 dose algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	LY2605541 Dosing Algorithm 1 + LY2605541 Dosing Algorithm 2 Algorithm 1: Participants took both LY2605541 and their pre-study insulin for first several days Algorithm 2: Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	91	176
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.64 (0.08)	-0.74 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.197
	Comments	The statistical significance level is 0.10.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.09
	Confidence Interval	(2-Sided) 90%; -0.21 to 0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

4. Secondary Outcome

Title	Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint
Description	HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Algorithm 1: Participants took both LY2605541 and their pre-study insulin for first several days Algorithm 2: Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	91	183
HbA1c <7.0%	48.4 52%	51.9 53%
HbA1c ≤6.5%	23.1 24.8%	29.5 30.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.609
	Comments	The statistical significance level is 0.10. P-value is for HbA1c <7.0%
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments	The statistical significance level is 0.10. P-value is for HbA1c ≤6.5%
	Method	Fisher Exact
	Comments

5. Secondary Outcome

Title	Percentage of Participants With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint Who Did Not Experience a Hypoglycemic Episode During Treatment
Description	HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 millimole/Liter (mmol/L) (≤70 milligram/deciliter [mg/dL]) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	LY2605541 Dosing Algorithm 1 + LY2605541 Dosing Algorithm 2 Algorithm 1: Participants took both LY2605541 and their pre-study insulin for first several days Algorithm 2: Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	92	188
HbA1c <7.0%	11.96 12.9%	16.49 16.8%
HbA1c ≤6.5%	6.52 7%	7.98 8.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.375
	Comments	The statistical significance level is 0.10. P-value is for HbA1c <7.0%.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.811
	Comments	The statistical significance level is 0.10. P- value is for HbA1c ≤6.5%
	Method	Fisher Exact
	Comments

6. Secondary Outcome

Title	8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint
Description	8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	LY2605541 Dosing Algorithm 1 + LY2605541 Dosing Algorithm 2 Algorithm 1: Participants took both LY2605541 and their pre-study insulin for first several days Algorithm 2: Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	92	191
Morning 2-hr postprandial BG	9.54 (0.31)	9.11 (0.25)
Midday Pre-meal BG	7.47 (0.28)	7.23 (0.23)
Midday 2-hr postprandial BG	9.49 (0.28)	9.22 (0.22)
Evening Pre-meal BG	7.92 (0.28)	7.80 (0.22)
Evening 2-hr postprandial BG	9.99 (0.30)	9.74 (0.24)
Bed time BG	9.44 (0.31)	9.15 (0.25)
0300 hours BG	7.26 (0.25)	7.36 (0.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.144
	Comments	The statistical significance level is 0.10. P- value is for morning 2-hr postprandial BG
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.43
	Confidence Interval	(2-Sided) 90%; -0.92 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.360
	Comments	The statistical significance level is 0.10. P-value is for midday pre-meal BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 90%; -0.70 to 0.20
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.342
	Comments	The statistical significance level is 0.10. P-value is for midday 2-hr postprandial BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.26
	Confidence Interval	(2-Sided) 90%; -0.72 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.654
	Comments	The statistical significance level is 0.10. P-value is for evening pre-meal BG
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 90%; -0.56 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.387
	Comments	The statistical significance level is 0.10. P-value is for evening 2-hr postprandial BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 90%; -0.73 to 0.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.339
	Comments	The statistical significance level is 0.10. P-value is for bed time BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 90%; -0.79 to 0.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.676
	Comments	The statistical significance level is 0.10. P-value is for 0300 hours BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	0.10
	Confidence Interval	(2-Sided) 90%; -0.30 to 0.50
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

7. Secondary Outcome

Title	Daily Basal Insulin Dose at Week 2 and Week 12
Description	LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time Frame	Week 2 and Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	LY2605541 Dosing Algorithm 1 + LY2605541 Dosing Algorithm 2 Algorithm 1: Participants took both LY2605541 and their pre-study insulin for first several days Algorithm 2: Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	92	188
Week 2	2.45 (0.15)	3.19 (0.12)
Week 12	2.90 (0.19)	4.58 (0.15)

8. Secondary Outcome

Title	Percentage of Participants With Hypoglycemia From Baseline Through Week 12
Description	Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]).
Time Frame	Baseline through Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	LY2605541 Dosing Algorithm 1 + LY2605541 Dosing Algorithm 2 Algorithm 1: Participants took both LY2605541 and their pre-study insulin for first several days Algorithm 2: Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	93	195
Number [percentage of participants]	63.4 68.2%	54.0 55.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.162
	Comments	The statistical significance level is 0.10.
	Method	Fisher Exact
	Comments

9. Secondary Outcome

Title	Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12
Description	Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk*30.
Time Frame	Baseline through Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	93	195
Mean (Standard Deviation) [Number of Hypoglycemia episodes/30 days]	1.52 (2.08)	1.34 (2.47)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.804
	Comments	The statistical significance level is 0.10.
	Method	Negative Binomial Model
	Comments

10. Secondary Outcome

Title	Percentage of Participants With Antibody Status Change From Baseline to Week 12 and Week 16
Description	Negative is defined as either 'negative' from lab or percent binding <1.16%. Positive is defined as the percent binding is ≥1.16%. The antibody status change is from negative to positive or positive to negative.
Time Frame	Week 12 and Week 16

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	93	98	97
Week 12 from negative to positive	2.4 2.6%	4.7 4.8%	2.8 2.9%
Week 12 from positive to negative	2.4 2.6%	0.0 0%	1.1 1.1%
Week 16 from negative to positive	2.4 2.6%	4.9 5%	3.5 3.6%
Week 16 from positive to negative	2.4 2.6%	0.0 0%	1.2 1.2%

11. Secondary Outcome

Title	Glycemic Variability in Fasting Blood Glucose at Baseline and Week 12
Description	Within-patient glycemic variability was assessed as the standard deviation of fasting blood glucose each day at baseline, and each day between Week 10 and Week 12. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1 and 2, glargine); dose conversion (pre-IA, post-IA); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time Frame	Baseline and Week12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Combined
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	92	191
Baseline	1.52 (0.11)	1.51 (0.09)
Week 12	1.23 (0.08)	1.20 (0.06)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.937
	Comments	The statistical significance level is 0.10. P-value is for baseline.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.01
	Confidence Interval	() 90%; -0.16 to 0.14
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.687
	Comments	The statistical significance level is 0.10. P-value is for Week 12.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 90%; -0.16 to 0.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY Combined - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

12. Secondary Outcome

Title	Pharmacokinetics - Drug (LY2605541) Concentration at Steady State (Css) at Week 12 Endpoint
Description	The drug (LY2605541) concentration at steady state (Css) is calculated from the clearance (Liter/hour) and the final dose of the participants. Clearance was estimated using population-based approaches.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LY2605541 Combined
Arm/Group Description	LY2605541 Dosing Algorithm 1 + LY2605541 Dosing Algorithm 2 Algorithm 1: Participants took both LY2605541 and their pre-study insulin for first several days Algorithm 2: Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	177
Geometric Mean (Geometric Coefficient of Variation) [picomoles per liter (pMol/L)]	4258 (70.8)

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	89	70	78
Least Squares Mean (Standard Error) [nmol/L]	-1.82 (0.23)	-2.22 (0.24)	-1.99 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.159
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 90%; -0.87 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.542
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 90%; -0.62 to 0.29
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

14. Secondary Outcome

Title	Change From Baseline in HbA1c at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Description	HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. LS mean of the change from baseline is from MMRM approach. MMRM model includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group); baseline HbA1c; visit; visit and treatment interaction; and a random effect for participant.
Time Frame	Baseline, Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	91	69	78
Least Squares Mean (Standard Error) [percentage of glycated hemoglobin]	-0.65 (0.07)	-0.67 (0.07)	-0.83 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.880
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 90%; -0.16 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.045
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 90%; -0.32 to -0.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

15. Secondary Outcome

Title	Percentage of Participants With HbA1c <7.0% and ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Description	HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	91	73	80
HbA1c <7.0%	48.4 52%	57.5 58.7%	50 51.5%
HbA1c ≤6.5%	23.1 24.8%	31.5 32.1%	26.3 27.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.273
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for HbA1c <7.0%.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.287
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for HbA1c ≤6.5%.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.879
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for HbA1c <7.0%.
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.722
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for HbA1c ≤6.5%.
	Method	Fisher Exact
	Comments

16. Secondary Outcome

Title	Percentage of Participants Who Did Not Experience a Hypoglycemic Episode During Treatment With HbA1c <7.0% and HbA1c ≤6.5% at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Description	HbA1c is a form of hemoglobin which is measured primarily to identify the average plasma glucose concentration over prolonged periods of time. Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]).
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	92	75	83
HbA1c <7.0%	11.96 12.9%	21.33 21.8%	15.66 16.1%
HbA1c ≤6.5%	6.52 7%	9.33 9.5%	7.23 7.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.139
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for HbA1c <7.0%.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.569
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for HbA1c ≤6.5%.
	Method	Fisher Exact
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.515
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for HbA1c <7.0%.
	Method	Fisher Exact
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	1.000
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for HbA1c ≤6.5%.
	Method	Fisher Exact
	Comments

17. Secondary Outcome

Title	8-Point Self-Monitored Blood Glucose (SMBG) Measures at Week 12 Endpoint - Subgroup Analysis of LY2605541 Dosing Algorithms
Description	8-point SMBG profiles are measured at morning FBG, midday pre-meal BG, evening pre-meal BG, 2-hour postprandial BG after each of the 3 main meals, bedtime BG, 0300 hours BG. LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	92	78	83
Morning pre-meal BG	6.76 (0.19)	7.02 (0.21)	6.62 (0.20)
Morning 2-hr postprandial BG	9.31 (0.27)	9.05 (0.29)	8.48 (0.28)
Midday Pre-meal BG	7.29 (0.26)	7.22 (0.27)	6.60 (0.26)
Midday 2-hr postprandial BG	9.36 (0.25)	8.96 (0.27)	9.09 (0.26)
Evening Pre-meal BG	7.79 (0.25)	7.64 (0.27)	7.64 (0.25)
Evening 2-hr postprandial BG	9.64 (0.26)	9.14 (0.28)	9.22 (0.27)
Bed time BG	9.13 (0.27)	8.86 (0.29)	8.43 (0.28)
0300 hours BG	7.10 (0.22)	7.34 (0.24)	6.82 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.305
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for morning pre-meal BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 90%; -0.16 to 0.67
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.571
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for morning pre-meal BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.14
	Confidence Interval	(2-Sided) 90%; -0.54 to 0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.454
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for morning 2-hr postprandial BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.26
	Confidence Interval	() 90%; -0.85 to 0.32
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.016
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for morning 2-hr postprandial BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.83
	Confidence Interval	(2-Sided) 90%; -1.40 to -0.26
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.838
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for midday pre-meal BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.07
	Confidence Interval	() 90%; -0.61 to 0.48
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.033
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for midday pre-meal BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.69
	Confidence Interval	(2-Sided) 90%; -1.22 to -0.16
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.229
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for midday 2-hr postprandial BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 90%; -0.95 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.412
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for midday 2-hr postprandial BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.27
	Confidence Interval	(2-Sided) 90%; -0.80 to 0.27
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.642
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for evening pre-meal BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.15
	Confidence Interval	(2-Sided) 90%; -0.68 to 0.38
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.614
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for evening pre-meal BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 90%; -0.67 to 0.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.147
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for evening 2-hr postprandial BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.50
	Confidence Interval	(2-Sided) 90%; -1.07 to 0.07
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.210
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for evening 2-hr postprandial BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.42
	Confidence Interval	(2-Sided) 90%; -0.98 to 0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 13

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.438
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for bed time BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 90%; -0.86 to 0.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 14

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.043
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for bed time BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.70
	Confidence Interval	(2-Sided) 90%; -1.28 to -0.13
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 15

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.403
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for 0300 hours BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	0.24
	Confidence Interval	(2-Sided) 90%; -0.23 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 16

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.314
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for 0300 hours BG.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.29
	Confidence Interval	(2-Sided) 90%; -0.75 to 0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

18. Secondary Outcome

Title	Daily Basal Insulin Dose at Week 2 and Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Description	LS mean is obtained using MMRM approach, which includes fixed effects of treatment (LY2605541 algorithm 1, LY2605541 algorithm 2, glargine); stratification variables (country, baseline daily basal insulin dose group, and baseline HbA1c group); visit; visit and treatment interaction; and a random effect for participant.
Time Frame	Week 2 and Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	92	76	81
Week 2	2.62 (0.13)	3.23 (0.13)	3.64 (0.13)
Week 12	3.15 (0.16)	4.58 (0.17)	5.26 (0.17)

19. Secondary Outcome

Title	Percentage of Participants With Hypoglycemia From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Description	Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]).
Time Frame	Baseline through Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	93	80	83
Number [percentage of participants]	63.4 68.2%	47.5 48.5%	54.2 55.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.046
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons.
	Method	Fisher Exact
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.224
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons.
	Method	Fisher Exact
	Comments

20. Secondary Outcome

Title	Rate of Hypoglycemia Per 30 Days From Baseline Through Week 12 - Subgroup Analysis of LY2605541 Dosing Algorithms
Description	Hypoglycemia episode is defined as any time a participant feels that he/she is experiencing a sign or symptom that is associated with hypoglycemia or has a BG level of ≤3.9 mmol/L (≤70 mg/dL) even if it was not associated with signs, symptoms, or treatment (consistent with current guidelines [ADA 2005]). Hypoglycemia rate per 30 days is calculated as the number of hypoglycemia/number of days at risk*30.
Time Frame	Baseline through Week 12

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	93	80	83
Mean (Standard Deviation) [Number of Hypoglycemia episodes/30 days]	1.52 (2.08)	1.25 (2.27)	1.27 (2.20)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.561
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons.
	Method	Negative Binomial Model
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.518
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons.
	Method	Negative Binomial Model
	Comments

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Insulin Glargine	LY2605541 Algorithm 1	LY2605541 Algorithm 2
Arm/Group Description	Subcutaneous injection of insulin glargine every morning with dose titration based on blood glucose measures for 12 weeks	Participants took both LY2605541 and their pre-study insulin for first several days Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks	Participants took only LY2605541 with first dose doubled Subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks
Measure Participants	92	77	83
Baseline	1.43 (0.07)	1.40 (0.08)	1.42 (0.07)
Week 12	1.17 (0.07)	1.16 (0.08)	1.07 (0.07)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.938
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for baseline.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 90%; -0.20 to 0.18
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.972
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for baseline.
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	0.00
	Confidence Interval	(2-Sided) 90%; -0.18 to 0.19
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 1
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.927
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for Week 12.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.01
	Confidence Interval	(2-Sided) 90%; -0.16 to 0.15
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 1 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Insulin Glargine, LY2605541 Algorithm 2
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.293
	Comments	The statistical significance level is 0.10 with no adjustments for multiple comparisons. P-value is for Week 12.
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Squares Mean Difference (Final)
	Estimated Value	-0.10
	Confidence Interval	(2-Sided) 90%; -0.25 to 0.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	The Least Squares Mean Difference = LY2605541 Algorithm 2 - Insulin Glargine; and 90% confidence interval (CI) = 90% CI of the least squares mean difference.

Adverse Events

Arm/Group Title	LY2605541 Dosing Algorithm 1		LY2605541 Dosing Algorithm 2		Insulin Glargine
Arm/Group Description	subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks		subcutaneous injection of LY2605541 every morning with dose titration based on blood glucose measures for 12 weeks		Subcutaneous injection of insulin Glargine every morning with dose titration based on blood glucose measures for 12 weeks
All Cause Mortality
	LY2605541 Dosing Algorithm 1		LY2605541 Dosing Algorithm 2		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LY2605541 Dosing Algorithm 1		LY2605541 Dosing Algorithm 2		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/98 (4.1%)		1/98 (1%)		2/93 (2.2%)
Cardiac disorders
Angina unstable	1/98 (1%)	1	1/98 (1%)	1	1/93 (1.1%)	1
Coronary artery disease	0/98 (0%)	0	0/98 (0%)	0	1/93 (1.1%)	1
Myocardial infarction	1/98 (1%)	1	1/98 (1%)	1	0/93 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/98 (1%)	1	0/98 (0%)	0	0/93 (0%)	0
Injury, poisoning and procedural complications
Foreign body	1/98 (1%)	1	0/98 (0%)	0	0/93 (0%)	0
Other (Not Including Serious) Adverse Events
	LY2605541 Dosing Algorithm 1		LY2605541 Dosing Algorithm 2		Insulin Glargine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	44/98 (44.9%)		47/98 (48%)		45/93 (48.4%)
Blood and lymphatic system disorders
Anaemia	2/98 (2%)	2	0/98 (0%)	0	0/93 (0%)	0
Leukocytosis	0/98 (0%)	0	2/98 (2%)	2	0/93 (0%)	0
Eye disorders
Eye pain	0/98 (0%)	0	3/98 (3.1%)	3	0/93 (0%)	0
Gastrointestinal disorders
Abdominal discomfort	0/98 (0%)	0	0/98 (0%)	0	2/93 (2.2%)	2
Abdominal pain upper	1/98 (1%)	1	0/98 (0%)	0	2/93 (2.2%)	2
Constipation	1/98 (1%)	1	2/98 (2%)	2	3/93 (3.2%)	3
Diarrhoea	3/98 (3.1%)	3	3/98 (3.1%)	3	3/93 (3.2%)	3
Gastrooesophageal reflux disease	0/98 (0%)	0	2/98 (2%)	2	0/93 (0%)	0
Nausea	2/98 (2%)	2	1/98 (1%)	1	2/93 (2.2%)	2
Vomiting	0/98 (0%)	0	1/98 (1%)	1	2/93 (2.2%)	2
General disorders
Asthenia	2/98 (2%)	2	0/98 (0%)	0	0/93 (0%)	0
Fatigue	2/98 (2%)	2	0/98 (0%)	0	1/93 (1.1%)	1
Infections and infestations
Bronchitis	1/98 (1%)	1	1/98 (1%)	1	2/93 (2.2%)	2
Influenza	3/98 (3.1%)	3	2/98 (2%)	2	0/93 (0%)	0
Nasopharyngitis	3/98 (3.1%)	3	6/98 (6.1%)	6	5/93 (5.4%)	6
Sinusitis	1/98 (1%)	1	0/98 (0%)	0	2/93 (2.2%)	2
Upper respiratory tract infection	2/98 (2%)	2	3/98 (3.1%)	3	3/93 (3.2%)	3
Urinary tract infection	0/98 (0%)	0	3/98 (3.1%)	3	0/93 (0%)	0
Viral infection	0/98 (0%)	0	2/98 (2%)	2	1/93 (1.1%)	1
Injury, poisoning and procedural complications
Contusion	2/98 (2%)	3	0/98 (0%)	0	0/93 (0%)	0
Investigations
Electrocardiogram QT prolonged	0/98 (0%)	0	0/98 (0%)	0	2/93 (2.2%)	2
Metabolism and nutrition disorders
Abnormal loss of weight	2/98 (2%)	2	4/98 (4.1%)	4	1/93 (1.1%)	1
Abnormal weight gain	0/98 (0%)	0	2/98 (2%)	3	3/93 (3.2%)	3
Dyslipidaemia	2/98 (2%)	2	1/98 (1%)	1	0/93 (0%)	0
Hypertriglyceridaemia	0/98 (0%)	0	2/98 (2%)	2	0/93 (0%)	0
Underweight	1/98 (1%)	1	4/98 (4.1%)	4	0/93 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	2/98 (2%)	2	2/98 (2%)	3	4/93 (4.3%)	4
Muscle spasms	1/98 (1%)	1	3/98 (3.1%)	3	0/93 (0%)	0
Pain in extremity	4/98 (4.1%)	4	1/98 (1%)	1	1/93 (1.1%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	2/98 (2%)	2	0/98 (0%)	0	0/93 (0%)	0
Nervous system disorders
Dizziness	3/98 (3.1%)	3	0/98 (0%)	0	1/93 (1.1%)	1
Headache	4/98 (4.1%)	4	2/98 (2%)	2	4/93 (4.3%)	6
Psychiatric disorders
Insomnia	2/98 (2%)	6	0/98 (0%)	0	0/93 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/98 (1%)	1	1/98 (1%)	1	2/93 (2.2%)	2
Skin and subcutaneous tissue disorders
Rash	0/98 (0%)	0	0/98 (0%)	0	2/93 (2.2%)	2
Urticaria	0/98 (0%)	0	2/98 (2%)	2	0/93 (0%)	0
Vascular disorders
Hypertension	0/98 (0%)	0	2/98 (2%)	2	0/93 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.