Composite endpoint comprised of progression to cirrhosis, development of large esophageal varices, gastric varices or development of varices needing treatment, development of ascites, development of hepatic encephalopathy, evidence of active or recent variceal hemorrhage, increase in model for end-stage liver disease (MELD) from ≤12 to ≥15, liver transplantation, all-cause mortality

Mean percent maintenance of BW reduction achieved during the 60-Week weight loss period will be measured in participants who have reached a BW plateau.

Percent change from baseline in body weight was reported. Least Squares (LS) mean was determined using ANCOVA model with Baseline + Baseline BMI Group 1 + Sex + Pre diabetes status at randomization + Treatment (Type III sum of squares) as variables.

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least squares (LS) mean was calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Baseline + SGLT2i Use (Yes/No) + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured

Time to first occurrence of any component event of composite, all-cause death, nonfatal MI, nonfatal stroke, coronary revascularization, or heart failure events that results in hospitalization or urgent visits.

AHI, Apnea-Hypopnea Index, is the number of apneas or hypopneas recorded via polysomnography during the study per hour of sleep. Apnea is defined as a cessation of airflow lasting at least 10 seconds, hypopnea as a decrease in airflow by at least 30% from baseline for at least 10 seconds occurring with a drop in oxygen saturation (SpO₂) by at least 4%. AHI values are categorized as 5-15 events/hr = mild; 15-\<30 events/hr = moderate; and ≥ 30 events/hr = severe. a significant reduction in values indicates a positive outcome.

Mean Percent Change from Baseline in Body Weight. Least squares (LS) mean was determined using mixed model repeated measures (MMRM) model with Baseline + Sex + Presence of Comorbidities + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Percentage of Participants who Achieve ≥5% Body Weight Reduction. A logistic regression model was used for this analysis.

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.

The KCCQ is a 23-item, participant self-administered questionnaire that assesses impacts of heart failure "over the past 2 weeks" on the following 7 domains: * Physical Limitation (6) * Symptom Stability (1) * Symptom Frequency (4) * Symptom Burden (3) * Self-Efficacy (2) * Quality of Life (3) * Social Limitation (4) Each of the 23 individual items are answered on Likert scales of varying lengths (5, 6, or 7-point scales). KCCQ-CSS includes the symptom and physical limitation domains of the KCCQ. Scores are obtained by averaging the associated individual items and transforming the score to a 0 to 100 range. Higher scores indicate better health status. Least Square (LS) mean was determined using ANCOVA model with Baseline + HF Decompensation Within 12 Months of Screening + T2DM Status + Baseline BMI group (\<35, \>=35 kg/m2) + Treatment (Type III sum of squares) as variables .

Clinical Endpoint Committe confirmed Occurrences of CV outcomes were reported here. HF outcomes consisted of cardiovascular death and HF events. The HF events were defined as worsening clinical symptoms or signs related to HF, which are meaningful to the participant and require intensification of treatment characterized by 1 or more of the following: * hospitalization for heart failure regardless of duration or treatment received * use of intravenous drug, usually an intravenous diuretic, but may include intravenous vasodilators or positive inotropic drugs, or * augmentation or increase in oral diuretic therapy.

Least square (LS) mean was analysed by mixed model repeated measures (MMRM) model with randomization + analysis country + sex + interactive web response system (IWRS) MTD at Week 36 + treatment + time + treatment\*time (Type III sum of squares) as variables.

Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression model using imputed data with baseline body weight, Analysis Country, Sex, Treatment as factors.

Percentage of participants who achieve ≥5% body weight reduction from baseline

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with covariates Baseline + Pooled Country + Baseline Metformin Use (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Number of participants with first occurrence of Clinical Endpoint Committee (CEC), a composite endpoint i.e., from time of randomization to first occurrence of cardiovascular (CV) death, myocardial infarction and stroke combined data was reported. Time to event was defined as the number of days from the date of randomization to the first occurrence of any of these events during the study follow-up period. Participants without an event were censored at their last known contact or end of follow-up.

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed model repeated measures (MMRM) model with covariates Baseline + Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus Sulfonylurea (SU)) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Least Squares (LS) Mean was calculated using mixed-model repeated measures (MMRM) with baseline, analysis country, sex, prediabetes status at randomization, treatment, time, treatment\*time (Type III sum of squares) in the model.

Percentage of participants who achieve greater than or equal to( ≥) 5% body weight reduction.

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Baseline Metformin Use (Yes, No) + Pooled Country + Treatment + Time + Treatment\*Time (Type III sum of squares).

An SAE is any AE from this study that results in one of the following outcomes: * Death * Initial or prolonged inpatient hospitalization * A life-threatening experience (that is, immediate risk of dying) * Persistent or significant disability/incapacity * Congenital anomaly/birth defect. * Important medical events that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the patient or may require. A summary of all SAE's, regardless of causality, is located in the Reported Adverse Events section.

To compare tirzepatide maximum tolerated dose (MTD) versus placebo from randomization to week 52 for percent initial weight loss

To compare tirzepatide MTD versus placebo from randomization to week 52 for reduction in the number of binge-eating episodes defined as change in the number of binge-eating episodes in the past 28 days measured via clinician interview

Using a multisizer, we will identify the size and distribution changes of fat cells from baseline to the end of the weight loss period to compare between tirzepatide administration and dietary restriction group

Using a Oil Red O and rtPCR, we will identify the fat storage capacity of fat cells from baseline to the end of the weight loss period to compare between tirzepatide administration and dietary restriction group

Using a DXA scan, we will measure the percentages of total, upper, lower, truncal, peripheral, and subcutaneous fat and compare it at baseline, 6 weeks, and 22 weeks for each participant

Compare direct measurement of insulin sensitivity after baseline, week 6, and week 22

NASH resolution is defined as the absence of fatty liver disease or simple steatosis without steatohepatitis; the absence of hepatocellular ballooning (nonalcoholic fatty liver disease (NAFLD) Activity Score (NAS) 0 for ballooning); with or without mild lobular inflammation (NAS 0 or 1 for inflammation); and any value for steatosis. No worsening of fibrosis is defined as no increase in fibrosis stage from baseline to Week 52.

Least squares (LS) mean was calculated using mixed model repeated measures model (MMRM) with baseline + baseline BMI group + baseline metformin flag + treatment + time + treatment\*time as fixed factors.

HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.This was a Bayesian dose response analysis of HbA1c (%) change from baseline. At baseline: Mean (SD = Standard Deviation) of baseline HbA1c (%). After baseline: Posterior Mean (SD = Posterior Standard Deviation) of HbA1c (%) change from baseline. The Least Squares Mean is Posterior mean.

A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.

PK: AUC (0-∞) of Tirzepatide excreted in Breastmilk

PK: Cmax of Tirzepatide

PK: AUC(0-t) of Tirzepatide

PK: AUC(0-∞) of Tirzepatide

Percentage of participants with TEAEs and SAEs were reported here. A summary of TEAEs, SAEs and other non-serious adverse events, regardless of causality, is located in the Reported Adverse Events section of this record.

The number of participants with one or more SAEs is assessed as related to the study drug and is summarized cumulatively. A serious adverse event is defined as an event that results in death, initial or prolonged hospitalization, is life-threatening, leads to persistent or significant disability/incapacity, is associated with congenital anomaly/birth defect, or is considered significant by the investigator for any other reason. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, is reported in the Reported Adverse Events module.

Area Under the Concentration Time Curve From Time Zero to Time T, Where T is the Last Time Point With a Measurable Concentration \[ AUC(0-tlast)\] of Acetaminophen

Maximum Observed Drug Concentration (cmax) of Acetaminophen

Change from baseline in calorie intake in participants receiving tirzepatide or placebo at week 3 is reported.

SMR was measured using whole-room indirect calorimetry (respiratory chamber). Change from Baseline to Week 18 in SMR was evaluated. Least square (LS) mean was determined by analysis of covariance (ANCOVA) model with Baseline, Treatment, Change from Baseline to Week 18 in Fat-Free Mass, Change from baseline to Week 18 in Fat Mass and Random Error as variables.

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Ethinylestradiol (EE)

PK: Cmax of EE

PK: Area Under the Concentration Versus Time Curve (AUC) Within 1 Dosing Interval (AUC\[0-tau\]) of Norelgestromin (NGMN)

PK: Cmax of Norelgestromin (NGMN)

A linear mixed effects model, with treatment, treatment period, and treatment sequence as fixed effects, and patient as a random effect using restricted maximum likelihood (REML) method was used. PG of plateau 100 mg/dL was considered as baseline timepoint.

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve of Tirzepatide From Time Zero to Infinity (AUC\[0-∞\]) was evaluated.

PK: Maximum Concentration (Cmax) of Tirzepatide was evaluated.

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve (AUC) of Tirzepatide from Time Zero to Infinity (AUC0toinf) was reported.

PK: Maximum Observed Plasma Concentration (Cmax) of Tirzepatide was reported

Pharmacokinetics (PK): Area Under The Drug Concentration-Time Curve From Zero To Infinity (AUC\[0-∞\]) of Tirzepatide.

PK: Maximum Observed Drug Concentration (Cmax) of Tirzepatide.

cDI is defined as the product of the M-value derived from the hyperinsulinemic euglycemic clamp over the last 30 minutes and total insulin secretion (ISR AUC0-120min) derived from the insulin secretion rate based on C-peptide using the using the deconvolution technique divided by the total glucose AUC0-120min from the hyperglycemic clamp portion of the study. Least squares (LS) mean was determined by analysis of covariance (ANCOVA) model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment (Type III sum of squares).

Pharmacokinetics (PK): Area Under the Concentration Versus Time Curve from Time Zero to tlast (AUC\[0-tlast\]) of Tirzepatide was evaluated.

Cmax is the maximum observed concentration of Tirzepatide.

Area Under the Concentration Versus Time Curve from Time Zero to Infinity (AUC\[0-inf\]) of Tirzepatide was evaluated.

Pharmacokinetics (PK) Part A: Area under the concentration versus time curve \[AUC (0-∞)\] of tirzepatide.

PK Part A: Maximum observed plasma drug concentration (Cmax) of tirzepatide.

PK Part B: Area under the concentration versus time curve \[AUC (0-∞)\] of tirzepatide.

Number of participants with one or more SAEs considered by the investigator to be related to study drug administration. A summary of SAEs and other non-serious adverse events (AEs), regardless of causality, were reported in the Reported Adverse Events module