A Study Comparing the Effect of Dulaglutide With Liraglutide in Type 2 Diabetes

Least Squares (LS) means of the glycosylated hemoglobin A1c (HbA1c) change from baseline to the primary endpoint at Week 26 was adjusted by fixed effects of treatment, country, visit, treatment-by-visit interaction, participant as random effect, and baseline HbA1c as covariates, via a mixed-effects model for repeated measures (MMRM) analysis using restricted maximum likelihood (REML).

Time frame: Baseline, 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable HbA1c data

The SMPG data were collected at the following 7 time points: pre-morning meal; 2 hours post-morning meal; pre-midday meal; 2 hours post-midday meal; pre-evening meal; 2 hours post-evening meal; and bedtime. The mean of the 7 time points (Daily Mean) was also calculated. LS means of the SMPG change from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, HbA1c strata, country, visit, treatment-by-visit interaction, participant as random effect and baseline SMPG as a covariate, via a MMRM analysis using REML.

Time frame: Baseline, 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable 7-Point SMPG data. Only pre-rescue measurements were used.

A summary of participants having changes in amylase evaluation from baseline to primary endpoint of 26 weeks is presented.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable amylase laboratory data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

Descriptive statistics for the actual measurements and change from baseline for sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. LS means of change from baseline were calculated using MMRM with treatment, country, visit, and treatment-by-visit interaction as fixed effects, baseline BP as a covariate, and participant as a random effect.

Time frame: Baseline, 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable BP data.

BMI is an estimate of body fat based on body weight divided by height squared. LS means of the BMI change from baseline to primary endpoint at Week 26 were calculated using ANCOVA with HbA1c Strata, country, and treatment as fixed effects and baseline BMI as a covariate.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable BMI data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.

LS means of the weight change from baseline to primary endpoint at Week 26 were calculated using analysis of covariance (ANCOVA) with HbA1c Strata, country, and treatment as fixed effects and baseline body weight as a covariate.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable body weight data. Only pre-rescue measurements were used. Last observation carried forward (LOCF) was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.

A summary of participants having changes in calcitonin values from baseline to primary endpoint of 26 weeks is presented.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable calcitonin laboratory data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

ECG HR was measured. LS means of change from baseline were analyzed using ANCOVA with HbA1c strata, country, and treatment as fixed effects and baseline HR as a covariate.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable ECG heart rate data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

The QT interval is a measure of the time between the start of the Q wave and the end of the T wave. QTcF is the measure of the time between the start of the Q wave and the end of the T wave adjusted using Fridericia's formula. PR is the interval between the P wave and the QRS complex. These parameters were calculated from electrocardiogram (ECG) data. LS means of change from baseline for the PR and QTcF intervals will be analyzed using the MMRM similar to MMRM model for primary outcome, using corresponding baseline and HbA1c strata. Only ECGs obtained at scheduled visits will be used in these summaries and analyses.

Time frame: Baseline, 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable ECG PR or QTcF interval data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

LS means of the FPG from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline FPG as covariates, via ANCOVA with LOCF.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable FPG data. Only pre-rescue measurements were used.~LOCF was used to impute missing postbaseline values. If no data after date of randomization, the endpoint was considered missing.

Descriptive statistics for the actual measurements and LS means of change from baseline for HR (sitting) by treatment arm were analyzed using the MMRM model with treatment, country, visit, and treatment-by-visit interaction as fixed effects, baseline rate as a covariate, and participant as a random effect.

Time frame: Baseline, 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable heart rate data.

The homeostatic model assessment (HOMA) quantifies insulin resistance and beta-cell function. HOMA2-%B is a computer model that uses fasting plasma insulin and glucose concentrations to estimate steady-state beta cell function (%B) as a percentage of a normal reference population (normal young adults). The normal reference population was set at 100%. LS means of the HOMA2-%B change from baseline to primary endpoint at Week 26 was adjusted by fixed effects of treatment, country, baseline HbA1c strata, and baseline HOMA2-%B value as covariate, via an ANCOVA analysis using LOCF.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable HOMA2-%B data. LOCF was used to impute missing postbaseline values. If there was no data after date of randomization, the endpoint was considered missing.

A summary of participants having changes in lipase evaluation from baseline to primary endpoint of 26 weeks is presented.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable lipase laboratory data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

The number of participants with events of pancreatitis confirmed by adjudication were summarized cumulatively at 26 weeks (including a 30-day follow up). Pancreatitis events were adjudicated by a committee of physicians external to the Sponsor. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Time frame: Baseline up to 30 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable adverse event data.

Allergic and hypersensitivity reactions that were considered possibly related to study drug by the investigator are presented. Serious and all other non-serious adverse events regardless of causality are summarized in the Reported Adverse Events module.

Time frame: Baseline through 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable adverse event data.

Deaths and nonfatal cardiovascular (CV) adverse events (AEs) were adjudicated by a committee of physicians with cardiology expertise external to the Sponsor. The nonfatal CV AEs to be adjudicated include myocardial infarction, hospitalization for unstable angina, hospitalization for heart failure, coronary interventions (such as coronary artery bypass graft or percutaneous coronary intervention), and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack. The number of participants with reported CV events, number of participants with nonfatal CV events confirmed by adjudication, and number of deaths confirmed by adjudication are summarized cumulatively at 26 weeks. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Time frame: Baseline up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable adjudicated CV event data.

LY2189265 (dulaglutide) anti-drug antibodies (ADA) were assessed at baseline, 26 weeks, and at the safety follow-up visit 4 weeks after study drug discontinuation in dulaglutide-treated participants. A participant was considered to have treatment emergent LY2189265 ADA if the participant had at least 1 titer that was treatment-emergent relative to baseline, defined as a 4-fold or greater increase in titer from baseline measurement. The number of participants with treatment-emergent LY2189265 ADA from postbaseline to follow up were summarized.

Time frame: Baseline up to 4 Weeks Post Last Dose of Study Drug

Population: Participants who were randomized and received at least 1 dose of LY2189265 with evaluable LY2189265 ADA data.

The percentage of participants who achieved the target HbA1c values at the primary endpoint were analyzed with a repeated logistic regression model (the generalized estimation equation \[GEE\] model). The model includes pooled country, treatment, visit, treatment-by-visit interaction, and baseline HbA1c as continuous covariates.

Time frame: Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or Liraglutide with evaluable HbA1c data. Only pre-rescue measurements were used. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation.

Time frame: Baseline through 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable concomitant medication data.

Hypoglycemic events (HE) were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a plasma glucose \[PG\] concentration of ≤70 mg/dL), asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL), nocturnal (events that occurred between bedtime and waking), or probable symptomatic (events during which symptoms of hypoglycemia were not accompanied by a PG determination but that was presumably caused by a PG of ≤70 mg/dL). A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Time frame: Baseline through 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable hypoglycemia event data. Only pre-rescue measurements were used.

A summary of percent change in lipid parameters (total cholesterol, high-density lipoprotein cholesterol \[HDL-C\], low density lipoprotein cholesterol \[LDL-C\], very low-density lipoprotein cholesterol \[VLDL\], and triglycerides) from baseline to primary endpoint of 26 weeks is presented. LS means of the lipid parameter from baseline to primary endpoint at Week 26 were adjusted by fixed effects of treatment, country, baseline HbA1c strata, and lipid parameter baseline as covariates, via ANCOVA with LOCF.

Time frame: Baseline, Up to 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable lipid laboratory data. LOCF was used to impute missing postbaseline values. If there were no data after the date of randomization, the endpoint was considered missing.

HE were classified as severe (episodes requiring the assistance of another person to actively administer resuscitative actions), documented symptomatic (any time a participant felt that he/she was experiencing symptoms and/or signs associated with hypoglycemia and had a PG concentration of ≤70 mg/dL), asymptomatic (events not accompanied by typical symptoms of hypoglycemia but with a measured PG of ≤ 70 mg/dL), nocturnal (events that occurred between bedtime and waking), or probable symptomatic (events during which symptoms of hypoglycemia were not accompanied by a PG determination but that was presumably caused by a PG of ≤70 mg/dL). The hypoglycemia rate per 30 days was calculated by the number of hypoglycemia events within the period/number of days participant at risk within the period\*30 days. A summary of serious and other non-serious adverse events regardless of causality is located in the Reported Adverse Events module.

Time frame: Baseline through 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable hypoglycemic episode data. Only pre-rescue measurements were used.

An additional intervention (rescue therapy) was defined as any additional therapeutic intervention in participants who developed persistent, severe hyperglycemia despite full compliance with the assigned therapeutic regimen, or initiation of an alternative antihyperglycemic medication following study drug discontinuation. Participants who had no rescue therapy within specified study period were considered as censored observations at the last available contact date up to specified study period.

Time frame: Baseline through 26 Weeks

Population: Participants who were randomized and received at least 1 dose of LY2189265 or liraglutide with evaluable concomitant medication data.