A Study to Evaluate Tirzepatide (LY3298176) in Pediatric and Adolescent Participants With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin or Basal Insulin or Both

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 ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares)

Time frame: Baseline, Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.This analysis was planned to measure the outcome by combining the 5 mg tirzepatide treatment arm and 10 mg tirzepatide treatment arm as pooled doses of tirzepatide (5 mg/10 mg).

BMI SDS (age and sex matched), calculated using the World Health Organization (WHO) growth reference standards. BMI is calculated as weight in kilograms divided by height in meters squared (kg/m²) and converted to a Z-score (SDS) based on WHO reference data. A Z-score of 0 represents the population mean for a given age and sex. A BMI SDS between -1 and +1 is considered normal. Obesity is defined as BMI SDS \> +2. Reductions in BMI SDS indicate improvement in weight status for individuals with obesity. LS mean was determined by the ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares)

Time frame: Baseline, Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to the study intervention or initiation of rescue antihyperglycemic medication.

LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares).

Time frame: Baseline, Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares).

Time frame: Baseline, Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

Height SDS (age and sex-matched), calculated using the World Health Organization (WHO) growth reference standards. Height SDS is derived by comparing a child's height to the median height for their age and sex in the WHO reference population, then expressing the difference in standard deviation units (Z-scores). A Z-score of 0 represents the population mean. A Height SDS below -2 indicates short stature. Positive changes in Height SDS from baseline reflect improvement in growth velocity or catch-up growth. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline Age group + Baseline Antihyperglycemic medication + Treatment + Time + Treatment\*Time(Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured

Time frame: Baseline, Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

The PedsQL Measurement Model measures health-related quality of life (HRQOL) in children (ages 8 to 12) and teenagers (ages 13 to 18). The 23-item PedsQL Generic Core Scale includes physical, emotional, social, and school functioning dimensions. The PedsQL Generic Core yields two summary scores: Physical Summary and Psychosocial Summary. Scores are transformed on a 0-100 scale, with higher scores indicating better functioning. Each item is scored from 0 (never) to 4 (almost always). Items are reverse scored and linearly transformed to a 0-100 scale so that higher scores indicate better HRQOL; the total score therefore ranges from 0 (worst) to 100 (best). Higher scores indicate better health-related quality of life. LS mean was determined by the MMRM model for post-baseline measures: Variable = Baseline + Baseline Antihyperglycemic Medication + Baseline Age Group + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured.

Time frame: Baseline, Week 52

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind, open-label, and safety follow-up periods regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

Weight SDS, calculated using Centers for Disease Control and Prevention (CDC) growth reference standards. Weight SDS is derived by comparing a child's weight to median weight for their age and sex in the CDC reference population, then expressing the difference in standard deviation units (Z-scores). A Z-score of 0 represents the population mean for a given age and sex. A Weight SDS below -2 may indicate underweight status, while a Weight SDS above +2 may indicate overweight or obesity. Change from baseline Weight SDS reflects shifts in growth trajectory, with positive changes indicating weight gain and negative changes indicating weight reduction. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline Age group + Baseline Antihyperglycemic medication + Treatment + Time + Treatment\*Time(Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured

Time frame: Baseline, Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

The PedsQL 3.2 Diabetes Module has 33 items for ages 13 years and older, and 32 items (1 less item for the Worry Scale) for ages 2 to 12 years. The 5 dimensions consist of diabetes symptoms (15 items), treatment barriers (5 items), treatment adherence (6 items), worry \[2 items (3 for teens and adults)\] and communication (4 items). Item scaling is a 5-point scale from 0 (never) to 4 (almost always). Items are reversed scored and linearly transformed to a 0-100 scale as follows: 0=100, 1=75, 2=50, 3=25, 4=0. Higher scores reflect fewer problems and better functioning. LS mean was determined by MMRM model for post-baseline measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment + Time + Treatment\*Time(Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance- Covariance structure (Change from Baseline) = Unstructured.

Time frame: Baseline, Week 52

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind, open-label, and safety follow-up periods regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.

Time frame: Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.

Time frame: Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.

Time frame: Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to the study intervention or initiation of rescue antihyperglycemic medication.

Geometric LS mean was determined by the MMRM model for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline Antihyperglycemic medication + Baseline Age group + Treatment + Time + Treatment\*Time (Type III sum of squares). Variance-Covariance structure (Change from Baseline) = Unstructured.

Time frame: Baseline, Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

LS mean was determined by ANCOVA model for endpoint measures: Variable = Baseline + Baseline Antihyperglycemic medication + Baseline Age group + Treatment (Type III sum of squares).

Time frame: Baseline, Week 30

Population: All randomized participants who received at least one dose of study drug and had evaluable data for this outcome obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.

The steady-state AUCs were estimated from Tirzepatide concentrations at Weeks 0, 7, 16, and 29 using the population PK model by treatment group.

Time frame: Week 0: after the first dose anytime on the same day. Weeks 7, 16, and 29: 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours post-dose, as assigned by IWRS.

Population: All randomized participants who received at least one dose of study drug and had evaluable PK data obtained during the double-blind period regardless of adherence to study intervention or initiation of rescue antihyperglycemic medication.