A Study of Once-Daily Oral Orforglipron (LY3502970) in Japanese Adult Participants With Obesity Disease

Values reported as "LS Mean" are model-based estimates (MBE) of the adjusted (unconditional) treatment effect. MBEs was calculated using an analysis of covariance (ANCOVA) model with the following variables: treatment group, baseline value, baseline Body Mass Index (BMI) category (<35 kilogram per meter square [kg/m²] or ≥35 kg/m²), and stratification factors (sex and baseline type 2 diabetes status). Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no).

Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression with the following variables: treatment group, baseline value, baseline BMI category (<35 kg/m² or ≥35 kg/m²), and stratification factors (sex and baseline type 2 diabetes status). Stratification factors were defined by the combination of sex (female, male) and baseline type 2 diabetes status (yes, no). The model also allowed the treatment effect to vary across baseline values and stratification factors.

Percentage of participants with ≥10% body weight reduction was analysed by Logistic regression with the following variables: treatment group, baseline value, baseline BMI category (<35 kg/m² or ≥35 kg/m²), and stratification factors (sex and baseline type 2 diabetes status). Stratification factors were defined by the combination of sex (female, male) and baseline type 2 diabetes status (yes, no). The model also allowed the treatment effect to vary across baseline values and stratification factors.

Percentage of participants with ≥15% body weight reduction was analysed by Logistic regression with the following variables: treatment group, baseline value, baseline BMI category (<35 kg/m² or ≥35 kg/m²), and stratification factors (sex and baseline type 2 diabetes status). Stratification factors were defined by the combination of sex (female, male) and baseline type 2 diabetes status (yes, no). The model also allowed the treatment effect to vary across baseline values and stratification factors.

Percentage of participants with ≥20% body weight reduction was analysed by Logistic regression with the following variables: treatment group, baseline value, baseline BMI category (<35 kg/m² or ≥35 kg/m²), and stratification factors (sex and baseline type 2 diabetes status). Stratification factors were defined by the combination of sex (female, male) and baseline type 2 diabetes status (yes, no). The model also allowed the treatment effect to vary across baseline values and stratification factors.

Values reported as "LS Mean" are model-based estimates (MBE) of the adjusted (unconditional) treatment effect. MBE was calculated using an ANCOVA model with the following variables: baseline, treatment, baseline BMI group, and strata in the model, including treatment-by-baseline and treatment-by-strata interaction terms. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no). The model also allowed the treatment effect to vary across baseline values and stratification factors.

Percentage of participants achieving hypertension improvement ((Systolic blood pressure <130 mmHg and diastolic blood pressure <80 mmHg) was analysed using logistic regression with the following variables: treatment, baseline BMI group, and strata in the model. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no). The estimates (odds ratio and corresponding confidence intervals) were derived using observed data.

Percentage of participants achieving dyslipidemia improvement (Low-density lipoprotein cholesterol <140 milligrams per deciliter (mg/dL), triglycerides <150 mg/dL, and high-density lipoprotein cholesterol ≥40 mg/dL) was analysed using logistic regression with the following variables: treatment, baseline BMI group, and strata in the model. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no). The estimates (odds ratio and corresponding confidence intervals) were derived using observed data.

Percentage of participants achieving HbA1c <6.5% was analysed using logistic regression with the following variables: baseline, treatment, baseline BMI group, and sex in the model, including treatment-by-baseline and treatment-by-sex interaction terms.

Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using an ANCOVA model with the following variables: baseline, treatment, baseline BMI group, and strata in the model, including treatment-by-baseline and treatment-by-strata interaction terms. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no).

Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using an ANCOVA model with the following variables: baseline, treatment, baseline BMI group, and strata in the model, including treatment-by-baseline and treatment-by-strata interaction terms. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no).

Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using an ANCOVA model with the following variables: baseline, treatment, baseline BMI group, and strata in the model, including treatment-by-baseline and treatment-by-strata interaction terms. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no).

Values represented as LS means are model-based estimates (MBE) of the unconditional average treatment effect on the log-transformed scale. MBE was calculated using an ANCOVA model for log(Actual Value/Baseline), including log-transformed baseline, treatment, baseline BMI group, and strata (defined by joint levels of sex [female, male] and baseline type 2 diabetes status [yes, no]) as covariates, with treatment-by-log(baseline) and treatment-by-strata interaction terms included in the model.

Values represented as LS means are model-based estimates (MBE) of the unconditional average treatment effect on the log-transformed scale. MBE was calculated using an ANCOVA model for log(Actual Value/Baseline), including log-transformed baseline, treatment, baseline BMI group, and strata (defined by joint levels of sex [female, male] and baseline type 2 diabetes status [yes, no]) as covariates, with treatment-by-log(baseline) and treatment-by-strata interaction terms included in the model.

Values represented as LS means are model-based estimates (MBE) of the unconditional average treatment effect on the log-transformed scale. MBE was calculated using an ANCOVA model for log(Actual Value/Baseline), including log-transformed baseline, treatment, baseline BMI group, and strata (defined by joint levels of sex [female, male] and baseline type 2 diabetes status [yes, no]) as covariates, with treatment-by-log(baseline) and treatment-by-strata interaction terms included in the model.

Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using an ANCOVA model with the following variables: baseline, treatment, baseline BMI group, and strata in the model, including treatment-by-baseline and treatment-by-strata interaction terms. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no).

• Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A, measured to reflect average plasma glucose concentration over prolonged periods of time.
• Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using an ANCOVA model with the following variables: baseline, treatment, baseline BMI group, and strata in the model, including treatment-by-baseline and treatment-by-strata interaction terms. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no).

Values represented under "LS Mean" are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed model for repeated measures (MMRM) with the following variables: baseline BMI group, baseline-by-time-by-treatment, and strata-by-time-by-treatment interaction terms in the model. Strata were defined by joint levels of sex (female, male) and baseline type 2 diabetes status (yes, no). An unstructured variance-covariance matrix was used.

Time to event was defined as the duration from randomization to adjudication committee-confirmed diagnosis of type 2 diabetes mellitus (T2D). Descriptive statistics are presented as Kaplan-Meier estimates of time to onset of T2D (in weeks). Time to onset of T2D was also analyzed using a Cox proportional hazards model, with treatment (pooled orforglipron dose groups) and sex as factors and baseline fasting serum glucose as a covariate. Hazard ratios with corresponding confidence intervals were estimated and reported in statistical analysis. Statistical significance between treatment groups was assessed using a two-sided log-rank test.

The SF-36v2 acute form, 1-week recall assesses participants' health-related quality of life on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Each domain is scored individually and information from these 8 domains is further aggregated into 2 health component summary scores, a Physical Component Summary, and a Mental Component Summary. Items are answered on Likert scales of varying lengths (3-point, 5-point, or 6-point scales). Scoring of each domain and both summary scores are norm based and presented in the form of T scores, with mean of 50 and standard deviation of 10; higher scores indicate better levels of function and/or better health. Range cannot be specified in norm-based scores.

The IWQOL-Lite-CT is a 20-item, obesity-specific patient reported outcome instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life: physical (7 items), and psychosocial (13 items). A 5-item subset of the physical domain, the physical-function composite is also supported. Items in the physical-function composite describe physical impacts related to general and specific physical activities. All items are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. The two domain scores (Physical and Psychosocial) and composite score (Physical function) range from 0 to 100 with higher scores indicating greater functioning. Raw scores are then linearly transformed to a 0 (worst) -100 (best) scale using: 100×(average item score-1)/4. Higher scores indicate better quality of life/function; lower scores indicate greater impairment.

Plasma concentrations of orforglipron were measured at predefined pre-dose and post-dose sampling time points.