Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise [D&E]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline glycosylated hemoglobin (HbA1c). Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline glycosylated hemoglobin (HbA1c) value.

Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise [D&E]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline glycosylated hemoglobin (HbA1c). Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with a baseline and at least 1 post-baseline glycosylated hemoglobin (HbA1c) value.

Standardized mixed-meal tolerance test (MMTT) used to assess changes in function of cells that make insulin (pancreatic beta cell function). Area under the plasma glucose concentration versus time curve calculated using linear-trapezoidal method. AUC for glucose represents area under curve of values when plotted over time. Larger area under the curve values represent greater average glucose value over time in response to meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline value and at least 1 post-baseline glucose area under the curve (AUC) value.

The area under the C-peptide concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for C-peptide represents area under the curve (AUC) of C-peptide values when plotted over time. Larger area under the curve (AUC) values represent a greater average C-peptide value over time in response to a meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit interaction. Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline C-peptide area under the curve (AUC) value.

Mixed meal tolerance test (MMTT) to assess changes in function of cells making insulin. AUCinsulin/AUCglucose ratio: index of insulin secretion. Larger values reflect greater secretion adjusted for glucose in response to meal. Area under insulin concentration versus time curve and area under plasma glucose concentration versus time curve calculated using linear-trapezoidal method. AUC for insulin and glucose represents AUC of values plotted over time. LS means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).

Intent-to-treat population (ITT): All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline AUC insulin/AUC glucose value. Reporting is on the 131 participants who received either TT223 or its placebo and reflects data only from the treatment and follow-up phases of the study.

Standardized mixed meal tolerance test (MMTT) to assess changes in hormones in response to meal. Area under the plasma glucagon concentration versus time curve was calculated using the linear-trapezoidal method. Area under the curve (AUC) for glucagon represents the AUC of glucagon values when are plotted over time. Larger area under the curve (AUC) values represent a greater average glucagon value over time in response to a meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a value at Week -1 and a value at that visit.

Standardized mixed meal tolerance test (MMTT) to assess changes in hormones in response to meal. Area under plasma glucagon-like peptide-1 (GLP-1) concentration versus time curve calculated using linear-trapezoidal method. Area under the curve (AUC) for glucagon-like peptide-1 (GLP-1) represents the AUC of GLP-1 values when plotted over time. Larger AUC values represent a greater average GLP-1 value over time in response to meal. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a value at Week -1 and a value at that visit.

Standardized MMTT to assess changes in function of cells that make insulin (pancreatic beta cells). Glucose measured at 2-hour timepoint during MMTT reflects glucose values in response to meal. Change in postprandial glucose calculated based on difference of 2-hour postprandial glucose at endpoint compared to baseline. Larger changes from baseline represent a greater postprandial glucose compared to 2-hour timepoint prior to treatment. Least squares (LS) means adjusted for baseline, treatment, visit, treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a value at Week -1 and a value at that visit and time point being assessed.

Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise [D&E]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline fasting blood glucose (FBG). Fasting blood glucose (FBG) is the mixed meal tolerance test (MMTT) glucose assessment at time point 0, where available, otherwise it is the assessment taken from the chemistry panel. Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with a baseline and at least 1 post-baseline fasting blood glucose (FBG) value.

HbA1c adjusted: baseline HbA1c (<8%,≥8%); C-peptide level (normal, elevated); HOMA (<baseline median,≥baseline median); duration diabetes (<3,3-10,>10 years); BMI (<30,≥30). BMI estimates body fat based on weight/height squared. HOMA: index of function of cells that make insulin/insulin resistance. Indices derived from fasting glucose and insulin concentrations. LS means adjusted for treatment, baseline therapy, visit, treatment-by-visit, subgroup, subgroup-by-treatment, subgroup-by-visit, subgroup-by-treatment-by-visit. Change from baseline=absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with a baseline and at least 1 post-baseline value.

Subgroup analyses for mixed meal tolerance test (MMTT) response (adjusted for baseline glycosylated hemoglobin (HbA1c), C-peptide level, Homeostasis Model Assessment of Insulin Resistance (HOMA), duration of diabetes, weight) not performed due to lack of statistically significant findings in subgroup analysis for HbA1c analyses. HOMA was not done for mixed meal tolerance test (MMTT) because it is not calculated from the mixed meal tolerance test (MMTT). It is reported separately as a secondary outcome measure. Change from baseline=absolute change from baseline (endpoint-baseline).

Because the subgroup analyses for MMTT response were not conducted due to the lack of statistically significant findings in the subgroup analysis for the HbA1c analyses, zero participants were analyzed.

The subgroup analyses for fasting blood glucose (FBG) (adjusted for baseline glycosylated hemoglobin [HbA1c]), C-peptide level, homeostasis model assessment of insulin resistance (HOMA), duration of diabetes, and weight) were not performed due to the lack of statistically significant findings in the subgroup analysis for the glycosylated hemoglobin (HbA1c) analyses. Change from baseline means the absolute change from baseline (endpoint-baseline).

Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise [D&E]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline weight. Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline weight value.

Participants who were positive for antibodies to LY2428757.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Participants who were positive for antibodies for TT223.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Time of maximum observed drug concentration (Tmax) is the time at which the maximum observed concentration (Cmax) occurs.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Half-life is the time it takes for the concentration of drug in plasma to decline by 50%.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Area under the curve (AUC)(0-infinity) = area under concentration versus time from zero to infinity. Area under the curve (AUC) is a measure of the total exposure to a drug.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Apparent total body clearance of drug calculated after extra-Vascular administration (CL/F) is the apparent volume of the body fluid cleared of the drug per unit of time, adjusted for how much drug goes into the body fluid.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

volume of distribution during the terminal phase after extra-vascular administration (Vz/F): Apparent volume that contains drug after absorption is complete and drug is no longer being given. Apparent volume of distribution at steady-State after extra-vascular administration (Vss/F): Apparent volume that contains drug when drug is being given continuously.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Time of maximum observed drug concentration (Tmax) is the time at which the maximum observed concentration (Cmax) occurs.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Half-life (t1/2) is the time it takes for the concentration of drug in plasma to decline by 50%.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Area under concentration versus time curve from zero to infinity (AUC[0-infinity]). Area under the curve (AUC) is a measure of the total exposure to a drug.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Apparent total body clearance of drug calculated after extra-vascular administration (CL/F) is the apparent volume of the body fluid cleared of the drug per unit of time, adjusted for how much drug goes into the body fluid.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Apparent volume of distribution during the terminal phase after extra-vascular administration (Vz/F) is the apparent volume that contains drug after absorption is complete and drug is no longer being given. Apparent volume of distribution at steady-state after extra-vascular administration (Vss/F) is the apparent volume that contains drug when drug is being given continuously.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Maximum observed drug concentration (Cmax) is the maximum observed concentration of drug. LY2428757 concentrations were collected at only a single timepoint; therefore, pharmacokinetic (PK) parameters could not be modeled from the data. Analysis was not done due to insufficient time points being collected.

Analyses were not conducted due to insufficient time points being collected; zero participants were analyzed.

The Visual Analog Scale (VAS) is a continuous measure for degree of nausea and/or gastrointestinal discomfort. Each of these scales is 100 millimeters (mm) in length with 0 meaning no nausea at all and 100 meaning extreme nausea. Participants record self-assessment of how much nausea they have had, from 0 to 100, during the time interval indicated.

Each visit includes participants who received at least 1 dose of TT223 or its placebo who had both a baseline value and a value at that visit.

Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

The 7-point average is the average of the mean value of all time points for the visit. Time points included pre-morning meal, 2 hours after morning meal, pre-midday meal, 2 hours after midday meal, pre-evening meal, 2 hours after evening meal, and bedtime.

Each visit includes participants who received at least 1 dose of TT223 or its placebo who had both a baseline value and a value at that visit.

7-point average=average of mean value of all time points for visit (premorning meal, 2-hours postmorning meal, premidday meal, 2-hours postmidday meal, preevening meal, 2-hours postevening meal, bedtime). Values represent mean of values collected same time on 3 separate days within week prior to visit. Values from repeated measures included fixed categorical effects: treatment, baseline therapy strata, visit, treatment-by-visit, continuous fixed covariate baseline <7-point average glucose value or time point presented. Change from baseline=absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value for the variable being analyzed.

Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline serum lipase. Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat (ITT): All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline amylase value.

Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline amylase.

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

Calculation of frequency of low glucose for time period. Hypoglycemia≥1 events: severe<50mg/dL, unable to treat self/recover after treatment; documented symptomatic≤70mg/dL, adrenergic/neuroglycopenic symptoms; asymptomatic≤70mg/dL no symptoms; probable symptomatic glucose missing, adrenergic/neuroglycopenic symptoms; relative>70mg/dL, adrenergic/neuroglycopenic symptoms, nocturnal≤70mg/dL, adrenergic/neuroglycopenic symptoms between bedtime/waking. Because number participants who experienced hypoglycemia was low for every arm (1-3/arm) did not model percentage participants with hypoglycemia.

Because the number of hypoglycemia events were too low to model the percentage of hypoglycemia, zero participants were analyzed.

The number of participants for whom low blood glucose was reported. Hypoglycemia ≥1 events including: severe hypoglycemia(glucose <50mg/dL, unable to treat self or recover after treatment); documented symptomatic (glucose ≤70mg/dL, adrenergic or neuroglycopenic symptoms); asymptomatic (glucose ≤70mg/dL no symptoms); probable symptomatic (glucose missing, adrenergic or neuroglycopenic symptoms); relative (glucose >70mg/dL, adrenergic or neuroglycopenic symptoms), nocturnal (glucose ≤70mg/dL, adrenergic or neuroglycopenic symptoms between bedtime/waking).

Intent-to-treat (ITT) population: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline value.

The protocol specified that deaths and nonfatal cardiovascular (CV) adverse events (AEs) be adjudicated by independent physician(s) with cardiology or neurology experience. The CV AEs to be adjudicated were protocol-defined as myocardial infarction (MI), hospitalization for unstable angina or for heart failure, coronary interventions (coronary artery bypass graft or percutaneous coronary intervention [PCI]) and cerebrovascular events including cerebrovascular accident (stroke) and transient ischemic attack (TIA). 3 CV events were adjudicated by an external independent adjudication committee.

All participants who received at least 1 dose of TT223 or its placebo.

Values obtained from repeated measures analysis, which included the fixed categorical effects of treatment, baseline therapy strata (metformin versus diet and exercise [D&E]), visit, and treatment-by-visit interaction, as well as the continuous, fixed covariate of baseline Fasting Insulin. Fasting insulin is the Mixed-Meal Tolerance Test (MMTT) insulin assessment at timepoint 0, where available, otherwise it is the assessment taken from the fasting laboratory measurements obtained during the clinic visit. Change from baseline means the absolute change from baseline (endpoint-baseline).

Intent-to-treat: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline fasting insulin value.

Values from repeated measures include fixed categorical effects of treatment, baseline therapy strata, visit, treatment-by-visit, continuous fixed covariate of baseline HOMA derived beta-cell function (HOMA-B). HOMA=index of function of cells that make insulin. Indices derived from fasting glucose and insulin concentrations. HOMA is measurement reflecting fasting plasma glucose and insulin. Has no defined minimum/maximum value. HOMA-B values generated from table reflecting values derived from Oxford HOMA2 model calculator. Change from baseline=absolute change from baseline (endpoint-baseline).

Intent-to-treat: All participants who received at least 1 dose of TT223 or its placebo with both a baseline and at least 1 post-baseline HOMA value.