A Study of Tirzepatide (LY3298176) in Participants With Obesity Disease

Mean percent change in body weight was measured. Least squares (LS) mean was determined using mixed model repeated measures (MMRM) model with Baseline + impaired glucose tolerance (IGT) at Screening + Hyperlipidemia at Screening + non-alcoholic fatty liver disease (NAFLD) at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Percentage of Participants Who Achieve ≥5% Body Weight Reduction

Percentage of participants who had improvement in obesity-related health problems

Change from Baseline in Fasting Glucose for Participants with IGT at Baseline. LS mean was determined by MMRM model with = Baseline + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Change from Baseline in OGTT 2-hr Glucose for Participants with IGT at Baseline. LS mean was determined by MMRM model with Baseline + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Percent Change from Baseline in Fasting Lipids TG for Participants with Hyperlipidemia at Baseline. LS mean was determined by MMRM model with log (Baseline) + NAFLD at Screening + IGT at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Percent Change from Baseline in HFF for participants diagnosed as NAFLD by MRI at Baseline. LS mean was determined by ANCOVA model with Baseline + Hyperlipidemia at Screening + IGT at Screening + Sex + Treatment (Type III sum of squares) as variables. Percent Change from Baseline in HFF for participants with NAFLD is reported. NAFLD was diagnosed by Magnetic Resonance Imaging (MRI) at Baseline. This was evaluated only for participants who were diagnosed with NAFLD at baseline by MRI.

Percentage of Participants Who Achieved Improvements of IGT. This was evaluated only for participants with IGT at baseline.

Percentage of Participants Who Achieved Improvements of Hyperlipidemia. This was evaluated only for participants with hyperlipidemia at baseline.

Percentage of Participants Who Achieved Improvements of NAFLD. This was evaluated only for participants who were diagnosed as NAFLD by MRI at Baseline.

Percentage of Participants Who Achieve ≥10% body weight reduction.

Percentage of Participants Who Achieve ≥15% body weight reduction.

Change from Baseline in Absolute Body Weight. LS mean was determined by MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Change from Baseline in BMI. LS mean was determined using MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Percent Change from Baseline in VAT. LS mean was determined by MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Percent Change from Baseline in SAT. LS mean was determined by MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Change from Baseline in VAT/SAT Ratio. LS mean was determined by MMRM model with Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Percentage of Participants Who Achieve VAT <100 cm² from Baseline for participants with VAT≥100 cm² at Baseline.

Change from Baseline in Waist Circumference. LS mean was determined using MMRM model with = Baseline + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Change from Baseline in HbA1c was assessed only for Participants with IGT at Baseline. LS mean was determined using MMRM model with = Baseline + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Change from Baseline in Fasting Insulin for Participants with IGT at Baseline. LS mean was determined using MMRM model log(Baseline) + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Change from Baseline in Systolic Blood Pressure. LS mean was determined using MMRM model with Baseline + Hyperlipidemia at Screening + NAFLD at Screening + IGT at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

Change from Baseline in Diastolic Blood Pressure. LS mean was determined using MMRM model with Baseline + Hyperlipidemia at Screening + NAFLD at Screening + IGT at Screening + Sex + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

The SF-36v2 acute form, 1-week recall assesses participants' health-related quality of life (HRQoL) on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. Information from these 8 domains is further aggregated into 2 health component summary scores: Physical Component Summary and Mental Component Summary.

Items are answered on Likert scales of varying lengths. Scoring of each domain and both summary scores are norm based and presented in the form of T scores, with a 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. LS mean was determined using ANCOVA model with Week 0 (Visit 3) + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment (Type III sum of squares) as variables.

The IWQOL Lite-CT consists of 20 items, assessing 2 primary domains of obesity related HRQoL: 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 in the physical domain 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. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better quality of life. LS mean was determined using ANCOVA model with Week 0 (Visit 3) + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment (Type III sum of squares) as variables.

The EQ-5D-5L is a standardized instrument used to measure self-reported health status of the participants. It comprises of 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). There are 5 response levels (no problems, slight problems, moderate problems, severe problems, unable to perform/extreme problems). In addition to the health profile, a single health state index value can be derived based on a formula that attaches weights to each of the levels in each dimension. This index value ranges between

˂0 (where 0 is a health state equivalent to death; negative values are valued as worse than dead) to 1 (perfect health). LS mean was determined using ANCOVA model with Week 0 (Visit 3) + IGT at Screening + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment (Type III sum of squares) as variables.