A Study to Compare a New Long-Acting Insulin (LY2605541)... | NCT01790438

ID	Type	Description	Link
I2R-MC-BIAK	Other Identifier	Eli Lilly and Company
2012-003941-13	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
LY2605541	Experimental	Administered by subcutaneous (SC) injection once daily in the morning or at bedtime. Initial dose is 10 units (or less for some of the participants in Korea) and is adjusted weekly based on Fasting Blood Glucose (FBG). LY2605541 will be given alone or in combination with up to 3 pre-study oral antihyperglycemic medications [OAM(s)] whose use is not excluded in combination with insulin. Treatment may last up to 26 weeks.	Drug: LY2605541 Drug: Oral Antihyperglycemic Medications (OAM)
Human Insulin NPH	Active Comparator	Administered by SC injection once daily at bedtime. Initial dose is 10 units (or less for some of the participants in Korea) and is adjusted weekly based on FBG. Human insulin NPH will be used alone or in combination with up to 3 pre-study OAM(s) whose use is not excluded in combination with insulin. Treatment may last up to 26 weeks. Some participants who are unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may be asked to add a second injection prior to the morning meal.	Drug: Human Insulin NPH Drug: Oral Antihyperglycemic Medications (OAM)

Name	Type	Description	Arm Group Labels	Other Names
LY2605541	Drug		LY2605541
Human Insulin NPH

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline to 26 Weeks in Hemoglobin A1c (HbA1c)	Glycosylated hemoglobin A1 (HbA1c) is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least Squares (LS) means were calculated by mixed model repeated measures (MMRM) using treatment, stratification factors (country, sulfonylureas/meglitinide use [Yes/No]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.	Baseline, 26 Weeks

Secondary Outcomes

Measure	Description	Time Frame
30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events	Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of <=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]). A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. Group mean rates of total and nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models with treatment, baseline sulfonylurea/meglitinide use, baseline event rate of the corresponding hypoglycemia as covariates, log (exposure/30 days) as the offset in the model. Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Have had type 2 diabetes mellitus for at least 1 year, not treated with insulin
Have been receiving 2 or more OAMs for at least 3 months prior to the study
Have a hemoglobin A1c (HbA1c) of 7.0% to 11.0%, inclusive, at screening
Have a body mass index (BMI) less than or equal to 45.0 kilograms per square meter (kg/m^2)
Women of childbearing potential are not breastfeeding, have a negative pregnancy test at screening and randomization, do not plan to become pregnant during the study, have practiced reliable birth control for at least 6 weeks prior to screening and will continue to do so during the study and until 2 weeks after the last dose of study drug

Exclusion Criteria:

Have used insulin therapy in the past 2 years (except for use during pregnancy or for short term use for acute conditions)
Have been treated with glucagon-like peptide-1 (GLP-1) receptor agonist, rosiglitazone, pramlintide, or weight-loss medication within 3 months before screening
For participants on OAMs: have any restrictions for cardiac, renal, and hepatic diseases in the local product regulations
Are taking, or have taken within the 90 days before screening, prescription or over-the-counter medications to promote weight loss
Have had any episodes of severe hypoglycemia, diabetic ketoacidosis, or hyperosmolar state/coma within 6 months prior to screening
Have cardiac disease with functional status that is New York Heart Association Class III or IV
Have a history of renal transplantation, or are currently receiving renal dialysis or have serum creatinine greater than or equal to 2 milligrams per deciliter (mg/dL) [177 millimoles per liter (mmol/L)]
Have obvious clinical signs or symptoms of liver disease [excluding nonalcoholic fatty liver disease (NAFLD)], acute or chronic hepatitis, nonalcoholic steatohepatitis (NASH), or elevated liver enzyme measurements
Have had a blood transfusion or severe blood loss within 3 months prior to screening or have known hemoglobinopathy, hemolytic anemia, or sickle cell anemia, or any other traits of hemoglobin abnormalities known to interfere with the measurement of HbA1c
Have active or untreated cancer, have been in remission from clinically significant cancer(other than basal cell or squamous cell skin cancer) for less than 5 years, or are at increased risk for developing cancer or a recurrence of cancer in the opinion of the investigator
Are receiving chronic (lasting longer than 14 consecutive days) systemic glucocorticoid therapy (excluding topical, intranasal, intraocular, and inhaled preparations) or have received such therapy within the 8 weeks immediately preceding screening
Have fasting triglycerides greater than 400 mg/dL (4.5 mmol/L) at screening
Have an irregular sleep/wake cycle (for example, participants who sleep during the day and work during the night) in the investigator's opinion
Are using or have used any of the following lipid-lowering medications: niacin preparations as a lipid-lowering medication and/or bile acid sequestrants within 90 days prior to screening

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

Facility	Status	City	State	ZIP	Country	Contacts
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.		Tempe	Arizona	85283

PubMed Identifier	Type	Citation	Retractions
36542287	Derived	Qu Y, White RD, Ruberg SJ. Accurate Collection of Reasons for Treatment Discontinuation to Better Define Estimands in Clinical Trials. Ther Innov Regul Sci. 2023 May;57(3):521-528. doi: 10.1007/s43441-022-00491-0. Epub 2022 Dec 21.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	LY2605541	Administered by subcutaneous (SC) injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on Fasting Blood Glucose (FBG). LY2605541 was given alone or in combination with up to 3 pre-study oral antihyperglycemic medications [OAM(s)] whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
BG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00058.86± 9.76 BG00159.79± 10.10 BG00259.17± 9.87

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG000209 BG001107 BG002

Ethnicity (NIH/OMB)

Participants who were not located in the United States were reported in the "Unknown or Not Reported" category for ethnicity.

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG000148 BG00173

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0001 BG0010 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG000112 BG00160 BG002

Body Mass Index (BMI)

Body mass index is an estimate of body fat based on body weight divided by height squared.

Mean

Standard Deviation

kilograms/square meters (kg/m^2)

Title

Denominators

Categories

Title	Measurements
	BG00030.80± 5.57 BG00131.04± 5.03

Duration of Diabetes

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00010.87± 6.46 BG00111.40± 7.01 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline to 26 Weeks in Hemoglobin A1c (HbA1c)

Glycosylated hemoglobin A1 (HbA1c) is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. Least Squares (LS) means were calculated by mixed model repeated measures (MMRM) using treatment, stratification factors (country, sulfonylureas/meglitinide use [Yes/No]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable HbA1c data.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

Baseline, 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Units	Counts
Participants	OG000420 OG001212

Title

Denominators

Categories

Title	Measurements
	OG000-1.73± 0.04 OG001-1.36± 0.06

Secondary

30-Day Adjusted Rate of Total and Nocturnal Hypoglycemic Events

Hypoglycemic episodes are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of <=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]). A nocturnal hypoglycemic event is defined as any total hypoglycemia event that occurred between bedtime and waking. Group mean rates of total and nocturnal hypoglycemia (per 30 days) are presented and were calculated from negative binomial regression models with treatment, baseline sulfonylurea/meglitinide use, baseline event rate of the corresponding hypoglycemia as covariates, log (exposure/30 days) as the offset in the model. Group Mean is estimated by taking the inverse link function on individual participant covariates first and then averages over all participants.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable hypoglycemic data at baseline and with at least one post-baseline value.

Posted

Mean

Standard Error

episodes per participant per 30 days

Baseline through 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH

Secondary

Percentage of Participants With HbA1c ≤6.5% and <7.0%

Percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable HbA1c data.

Posted

Number

Percentage of Participants

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Fasting Serum Glucose (FSG) (by Laboratory)

LS means were calculated from MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use [Yes/No]), baseline HbA1c strata [≤8.5% or >8.5%]), visit, treatment-by-visit interaction, and baseline value of the response variable as the fixed effects.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable FSG.

Posted

Least Squares Mean

Standard Error

milligrams per deciliter (mg/dL)

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Fasting Blood Glucose (FBG) (by Self Monitoring)

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable FBG data.

Posted

Least Squares Mean

Standard Error

milligrams per deciliter (mg/dL)

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

6-Point Self-Monitored Blood Glucose (SMBG)

6-point SMBG profiles were obtained on 3 nonconsecutive days in the week prior to Weeks 0, 4, 8, 12, 16, and 26. The SMBG measurements were performed while fasting (prior to the morning meal [breakfast]), prior to the midday meal (lunch), prior to the evening meal (dinner), at bedtime, at approximately 0300 hours, and the next day fasting (prior to the morning meal). LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use [Yes/No]), ], baseline HbA1c strata [≤8.5% or >8.5%]), visit, treatment-by-visit interaction, and baseline SMBG at the same time point of the response variable as the fixed effects.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable blood glucose data.

Posted

Least Squares Mean

Standard Error

mg/dL

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Change From Baseline to 26 Weeks in Body Weight

LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use [Yes/No]), baseline HbA1c strata [≤8.5% or >8.5%]), visit, treatment-by-visit interaction, and baseline weight as the fixed effects.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable body weight data.

Posted

Least Squares Mean

Standard Error

kilograms (kg)

Baseline, 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

HbA1c

HbA1c is a test that measures a participant's average blood glucose level over a 2 to 3 month timeframe. LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use [Yes/No]), visit, treatment-by-visit interaction, and baseline HbA1c as the fixed effects.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable HbA1c data.

Posted

Least Squares Mean

Standard Error

percentage of HbA1c

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Insulin Dose Per Kilogram (kg) of Body Weight

LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use [Yes/No]), baseline HbA1c strata [≤8.5% or >8.5%]), visit, and treatment-by-visit interaction as the fixed effects.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable insulin dose and body weight data.

Posted

Least Squares Mean

Standard Error

units per kilogram

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Time to Steady-State (Stable Maximum Dose)

Steady-state was defined as the first local maximum dose (peak dose value) of LY2605541 or human insulin NPH within the window of -2 to +2 weeks. The median time to steady-state of basal insulin dose estimated from Kaplan-Meier analysis was summarized by treatment.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable steady state data.

Posted

Median

95% Confidence Interval

weeks

Baseline through 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Change From Baseline to 26 Weeks in European Quality of Life - 5 Dimension 3 Levels (EQ-5D-3L) Index

The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. The profile allows participants to rate their health state in 5 health domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression using a three level scale 1-3 (no problem, some problems, and extreme problems). These combinations of attributes were converted into a weighted health-state Index Score according to the United States (US) population-based algorithm. The EQ-5D-3L US based index scores ranged from -0.11 to 1.0 where a score of 1.0 indicates perfect health. LS means were calculated from ANCOVA using treatment, stratification factor (country, baseline sulfonylurea sulfonylureas/meglitinide use [Yes/No], baseline HbA1c strata [≤8.5% or >8.5%]) and baseline value of EQ-5D-3Las covariates.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable EQ-5D-3L data. Missing endpoints were imputed with the last observation carried forward (LOCF) method.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH

Secondary

Insulin Treatment Satisfaction Questionnaire (ITSQ) Score

ITSQ is a validated instrument containing 22 items that assess treatment satisfaction for participants with diabetes and on insulin. The questionnaire measures satisfaction from the following 5 domains: Inconvenience of Regimen, Lifestyle Flexibility, Glycemic Control, Hypoglycemic Control, Insulin Delivery Device. Data presented are the transformed score on a scale of 0-100, higher scores indicate better treatment satisfaction. LS means were calculated using analysis of variance (ANOVA) adjusting for treatment and stratification factors (country, baseline sulfonylureas/meglitinide use [Yes/No], baseline HbA1c [≤8.5% or >8.5%]).

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable ITSQ data. Missing endpoints were imputed with the LOCF method.

Posted

Least Squares Mean

Standard Error

units on a scale

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Change From Baseline to 26 Weeks in Adult Low Blood Sugar Survey (LBSS) Scores

Adult LBSS (also referenced as Hypoglycemia Fear Survey - II [HFS-II]) contains 33 items, with each item scored on a 5-point response scale: 0 (never) to 4 (always). Items are categorized in 2 domains: Behavior (or avoidance) with 15 items and Worry (or affect) with 18 items. Sum all the items to obtain a total score (range 0-132). Higher total scores reflect greater fear of hypoglycemia. LS means were calculated using analysis of covariance (ANCOVA) adjusting for treatment, stratification factor (country, baseline sulfonylureas/meglitinide use [Yes/No]), baseline HbA1c (≤8.5% or >8.5%), and baseline value of LBSS.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable LBSS data. Missing endpoints were imputed with the LOCF method.

Posted

Least Squares Mean

Standard Error

units on a scale

Baseline, 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Change From Baseline to 26 Weeks in Lipid Profile

Lipid profile includes total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides. LS means for post-baseline measures were calculated using MMRM with the fixed effects of stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, sulfonylureas/meglitinide use, and LDL-C [<100 mg/dL and ≥100 mg/dL], except for the LDL-C outcome variable), visit, treatment, visit-by-treatment interaction, and baseline value of corresponding lipid outcome variable. LS means for End Of Study measures were calculated using ANCOVA adjusting for stratification factors (baseline HbA1c [≤8.5% and >8.5%], country, sulfonylureas/meglitinide use, and LDL-C [<100 mg/dL and ≥100 mg/dL]except for the LDL-C outcome variable), treatment, and baseline value of corresponding lipid outcome variable.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable lipid data. Missing endpoints for End Of Study measures were imputed with the LOCF method.

Posted

Least Squares Mean

Standard Error

mg/dL

Baseline, 26 Weeks; Baseline, End Of Study (EOS) (Up to 30 Weeks)

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH

Secondary

Percentage of Participants With Insulin Antibodies

The percentage of participants with a positive treatment-emergent anti-LY2605541 antibody response (TEAR) is summarized. TEAR was defined as change from baseline to postbaseline in the anti-LY2605541 antibody level either (1) from undetectable to detectable or (2) from detectable to the value with at least 130% relative increase from baseline. Percentage of participants was calculated by dividing the number of participants with TEAR anytime during the treatment period by the total number of participants analyzed, multiplied by 100.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable anti-drug (LY2605541) antibodies (ADA) data.

Posted

Number

percentage of participants

Baseline to 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Intra-Participant Variability in FBG by Standard Deviation

Glucose variability was assessed by between-day variability as measured by the standard deviation or the coefficient of variation of the FBG of the last 7 days prior to the visit using SMBG. LS means were calculated by MMRM using treatment, stratification factors (country, sulfonylureas/meglitinide use [Yes/No], baseline HbA1c strata [≤8.5% or >8.5%]), visit, treatment-by-visit interaction, and baseline FBG variability as the fixed effects.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable FBG data.

Posted

Least Squares Mean

Standard Deviation

mg/dL

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Intra-Participant Variability in FBG by the Coefficient of Variation

Glucose variability was assessed by between-day variability as measured by the standard deviation or the coefficient of variation of the FBG of the last 7 days prior to the visit using SMBG.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable FBG data.

Posted

Geometric Mean

Geometric Coefficient of Variation

mg/dL

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Percentage of Participants With Total and Nocturnal Hypoglycemic Events

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable hypoglycemic data at baseline and with at least one post-baseline value.

Posted

Number

percentage of participants

Baseline through 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Percentage of Participants With HbA1c <7.0% and Without Nocturnal Hypoglycemia

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable HbA1c data and hypoglycemia data.

Posted

Number

percentage of participants

26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Percentage of Participants With Injection Site Reactions

The percentage of participants with at least one treatment-emergent injection site reaction is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Participants who received at least one dose of LY2605541 or human insulin NPH.

Posted

Number

percentage of participants

Baseline through 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose is 10 units and is adjusted weekly based on FBG. LY2605541 will be given alone or in combination with up to 3 pre-study OAM(s) whose use is not excluded in combination with insulin. Treatment may last up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose is 10 units and is adjusted weekly based on FBG. Human insulin NPH will be used alone or in combination with up to 3 pre-study OAM(s) whose use is not excluded in combination with insulin. Treatment may last up to 26 weeks. Some participants who are unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may be asked to add a second injection prior to the morning meal.

Secondary

Rate of Severe Hypoglycemic Events

Hypoglycemic event are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of <=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]). A severe hypoglycemic event was defined as a hypoglycemic episode requiring assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions. The hypoglycemia rate per 100 years during a defined period was calculated by the number of hypoglycemia events within the period divided by the number of days participant at risk within the period*36525 days.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable hypoglycemic data at baseline and with at least one post-baseline value.

Posted

Mean

Standard Deviation

events per 100 participant years

Baseline through 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Percentage of Participants With Severe Hypoglycemic Events

Hypoglycemic event are defined as an event which is associated with reported signs and symptoms of hypoglycemia, and/or a documented blood glucose (BG) concentration of <=70 milligram per deciliter (mg/dL) (3.9 millimoles per liter [mmol/L]). A severe hypoglycemic event was defined as a hypoglycemic episode requiring assistance of another person to actively administer carbohydrates, glucagon, or other resuscitative actions. The percentage of participants with at least one severe hypoglycemia is presented. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable hypoglycemic data at baseline and with at least one post-baseline value.

Posted

Number

percentage of participants

Baseline through 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Secondary

Change From Baseline to 26 Weeks in European Quality of Life (EQ-5D-3L) - Visual Analog Scales (VAS) Scores

The EQ-5D-3L is a generic, multidimensional, health-related, quality-of-life instrument. Overall health state score was self-reported using a visual analogue scale (VAS) marked on a scale of 0 to 100 with 0 representing worst imaginable health state and 100 representing best imaginable health state.

Participants who received at least one dose of LY2605541 or human insulin NPH with evaluable EuroQol-5D-3L data.

Posted

Mean

Standard Deviation

units on a scale

Baseline, 26 Weeks

ID	Title	Description
OG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.
OG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	LY2605541	Administered by SC injection once daily in the morning or at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. LY2605541 was given alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks.			28	427	228	427
EG001	Human Insulin NPH	Administered by SC injection once daily at bedtime. Initial dose was 10 units and was adjusted weekly based on FBG. Human insulin NPH was used alone or in combination with up to 3 pre-study OAM(s) whose use was not excluded in combination with insulin. Treatment may have lasted up to 26 weeks. Some participants who were unable to achieve glycemic control after at least 12 weeks of treatment with a single injection of NPH may have been asked to add a second injection prior to the morning meal.			9	212	111	212

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Acute myocardial infarction	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Angina unstable	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Atrial flutter	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0002 events1 affected427 at risk EG0010 events0 affected212 at risk
Atrioventricular block	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Cardiac arrest	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Cardiac failure	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0003 events2 affected427 at risk EG0010 events0 affected212 at risk
Cardiac failure congestive	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0002 events2 affected427 at risk EG0010 events0 affected212 at risk
Coronary artery insufficiency	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected427 at risk EG0013 events1 affected212 at risk
Myocardial ischaemia	Cardiac disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected427 at risk EG0011 events1 affected212 at risk
Nausea	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected427 at risk EG0011 events1 affected212 at risk
Vomiting	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Non-cardiac chest pain	General disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Sudden death	General disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Ulcer	General disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA 16.0	Systematic Assessment	EG0002 events1 affected427 at risk EG0010 events0 affected212 at risk
Abdominal wall abscess	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected427 at risk EG0011 events1 affected212 at risk
Bronchitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Cellulitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Hepatitis C	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Meningitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Pneumonia	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Fall	Injury, poisoning and procedural complications	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected427 at risk EG0011 events1 affected212 at risk
Radius fracture	Injury, poisoning and procedural complications	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected427 at risk EG0011 events1 affected212 at risk
Alanine aminotransferase increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0012 events1 affected212 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0012 events1 affected212 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0002 events2 affected427 at risk EG0010 events0 affected212 at risk
Intervertebral disc disorder	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0004 events1 affected427 at risk EG0010 events0 affected212 at risk
Glioblastoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Malignant peritoneal neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Non-Hodgkin's lymphoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Ovarian neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0011 events1 affected107 at risk
Squamous cell carcinoma of skin	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Carotid artery stenosis	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected427 at risk EG0011 events1 affected212 at risk
Syncope	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Depression	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0004 events2 affected427 at risk EG0010 events0 affected212 at risk
Suicidal ideation	Psychiatric disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Calculus ureteric	Renal and urinary disorders	MedDRA 16.0	Systematic Assessment	EG0002 events2 affected427 at risk EG0010 events0 affected212 at risk
Uterovaginal prolapse	Reproductive system and breast disorders	MedDRA 16.0	Systematic Assessment	EG0000 events0 affected209 at risk EG0012 events1 affected107 at risk
Sleep apnoea syndrome	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0010 events0 affected212 at risk
Psoriasis	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0003 events1 affected427 at risk EG0010 events0 affected212 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal pain upper	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0002 events2 affected427 at risk EG0013 events3 affected212 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG00016 events13 affected427 at risk EG0019 events6 affected212 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0002 events2 affected427 at risk EG0018 events5 affected212 at risk
Nausea	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0006 events6 affected427 at risk EG0015 events3 affected212 at risk
Toothache	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0006 events6 affected427 at risk EG0010 events0 affected212 at risk
Vomiting	Gastrointestinal disorders	MedDRA 16.0	Systematic Assessment	EG0005 events5 affected427 at risk EG0013 events3 affected212 at risk
Fatigue	General disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0015 events5 affected212 at risk
Oedema peripheral	General disorders	MedDRA 16.0	Systematic Assessment	EG00014 events11 affected427 at risk EG0013 events3 affected212 at risk
Bronchitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0008 events8 affected427 at risk EG0014 events4 affected212 at risk
Herpes zoster	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0002 events2 affected427 at risk EG0013 events3 affected212 at risk
Influenza	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0008 events7 affected427 at risk EG0018 events7 affected212 at risk
Nasopharyngitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG00039 events29 affected427 at risk EG00134 events23 affected212 at risk
Sinusitis	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0007 events6 affected427 at risk EG0017 events5 affected212 at risk
Tooth infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG0005 events5 affected427 at risk EG0010 events0 affected212 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG00023 events18 affected427 at risk EG0015 events5 affected212 at risk
Urinary tract infection	Infections and infestations	MedDRA 16.0	Systematic Assessment	EG00014 events10 affected427 at risk EG0015 events4 affected212 at risk
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 16.0	Systematic Assessment	EG0005 events5 affected427 at risk EG0010 events0 affected212 at risk
Alanine aminotransferase increased	Investigations	MedDRA 16.0	Systematic Assessment	EG0008 events6 affected427 at risk EG0012 events2 affected212 at risk
Weight increased	Investigations	MedDRA 16.0	Systematic Assessment	EG00015 events14 affected427 at risk EG0015 events5 affected212 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 16.0	Systematic Assessment	EG0005 events5 affected427 at risk EG0010 events0 affected212 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0003 events3 affected427 at risk EG0017 events6 affected212 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG00017 events16 affected427 at risk EG00110 events8 affected212 at risk
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG0006 events6 affected427 at risk EG0010 events0 affected212 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 16.0	Systematic Assessment	EG00011 events11 affected427 at risk EG0016 events3 affected212 at risk
Dizziness	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0004 events4 affected427 at risk EG0018 events7 affected212 at risk
Headache	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG00030 events23 affected427 at risk EG00117 events9 affected212 at risk
Hypoaesthesia	Nervous system disorders	MedDRA 16.0	Systematic Assessment	EG0006 events6 affected427 at risk EG0010 events0 affected212 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG00012 events11 affected427 at risk EG00111 events11 affected212 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 16.0	Systematic Assessment	EG0008 events8 affected427 at risk EG0015 events4 affected212 at risk
Lipohypertrophy	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0001 events1 affected427 at risk EG0014 events3 affected212 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 16.0	Systematic Assessment	EG0004 events4 affected427 at risk EG0013 events3 affected212 at risk
Hypertension	Vascular disorders	MedDRA 16.0	Systematic Assessment	EG0006 events6 affected427 at risk EG0011 events1 affected212 at risk

ID	Term
D003920	Diabetes Mellitus
D044882	Glucose Metabolism Disorders
D008659	Metabolic Diseases
D009750	Nutritional and Metabolic Diseases
D004700	Endocrine System Diseases

ID	Term
D049528	Insulin, Long-Acting
D061385	Insulins
D010187	Pancreatic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins