A Study of Insulin Efsitora Alfa (LY3209590) Compared to Degludec in Adults With Type 2 Diabetes Who Are Starting Basal Insulin for the First Time

• HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.
• Least Squares (LS) mean was determined using Analysis of Covariance (ANCOVA) model with Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputations approach.

• HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.
• LS mean was determined using ANCOVA model with Baseline + Country + SU Use at Randomization Flag + Treatment (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputations approach.

• HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.
• LS mean was determined using ANCOVA model with Baseline + Country + SU Use at Randomization Flag + Treatment (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputations approach.

• HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.
• LS mean was determined using ANCOVA model with Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment (Type III sum of squares) as variables. Missing data at Week 52 were imputed by return-to-baseline multiple imputations approach.

• Percentage of time spent within the blood glucose range of 70 to 180 milligrams per deciliter (mg/dL) [3.9 to 10.0 millimoles per liter (mmol/L)], as measured during the continuous glucose monitoring (CGM) session over a 24-hour period, from Week 48 to Week 52.
• LS mean was determined using ANCOVA model with Baseline + Country + HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization + SU Use at Randomization + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed using multiple imputation under the assumption of missing at random, while missing data at Week 48-52 were imputed using a return-to-baseline multiple imputation approach.

• HbA1c is the glycosylated fraction of hemoglobin A. It is measured to identify average plasma glucose concentration over prolonged periods of time.
• LS mean was determined using ANCOVA model with Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment (Type III sum of squares) as variables. Missing data at Week 26 were imputed by return-to-baseline multiple imputations approach.

• Percentage of time spent within the blood glucose range of 70 to 180 mg/dL (3.9 to 10.0 mmol/L), as measured during the CGM session over a 24-hour period, from Week 22 to Week 26.
• LS mean was determined using ANCOVA model with Baseline + Country + HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization + SU Use at Randomization + Treatment (Type III sum of squares) as variables. Missing data at baseline were imputed using multiple imputation under the assumption of missing at random, while missing data at Week 22-26 were imputed using a return-to-baseline multiple imputation approach.

Change from baseline in fasting blood glucose measured by self-monitoring blood glucose (SMBG).

• Glucose variability measured as coefficient of variation (CV) for blood glucose during the CGM session over a 24-hour period, between Week 22 to Week 26 and Week 48 to Week 52 was reported.
• LS mean was determined using Mixed Model Repeated Measures (MMRM) model with Baseline + Country +HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

• The insulin dose was calculated based on the participant's entry of daily or weekly insulin doses in an electronic diary. The average weekly basal insulin dose at Week 26 and Week 52 was reported.
• LS mean was determined using MMRM model with Country + HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

• A hypoglycemic event with blood glucose (BG) levels of less than (<) 54 mg/dL (3.0 mmol/L) [Level 2] or Severe Hypoglycemia [Level 3] was reported. A severe hypoglycemic event was characterized by altered mental or physical status, requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions for the treatment of hypoglycemia.
• Group mean was reported and determined by Negative binomial model using Number of episodes = HbA1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.

• The event rate of participant-reported clinically significant nocturnal hypoglycemia (defined as blood glucose level <54 mg/dL (3.0 mmol/L) or severe hypoglycemia and occurs at night and presumably during sleep between midnight and 6:00 AM), measured during treatment phase up to week 52.
• Group mean was reported and determined by Negative binomial model using Number of episodes = HbA1c at Baseline (%) + Treatment, with log (exposure in days/365.25) as an offset variable.

Change from baseline in body weight was reported. LS mean was determined by MMRM model with Baseline + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

• Percentage of time spent in the hypoglycemia range with blood glucose <70 mg/dL (3.9 mmol/L), as measured during the CGM session over a 24-hour period from Week 8 to Week 12, Week 22 to Week 26, and Week 48 to Week 52 was reported.
• LS mean was determined using MMRM model with Baseline + HbA1c Stratum at Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

• Percentage of time spent in the hypoglycemia range with blood glucose < 54 mg/dL (3.0 mmol/L), as measured during the CGM session over a 24-hour period from Week 8 to Week 12, Week 22 to Week 26, and Week 48 to Week 52, was reported.
• LS mean was determined using MMRM model with Baseline + HbA1c Stratum at Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

• Percentage of time spent in the hyperglycemia range with blood glucose greater than (>) 180 mg/dL (10.0 mmol/L), as measured during the CGM session over a 24-hour period from Week 8 to Week 12, Week 22 to Week 26, and Week 48 to Week 52 was reported.
• LS mean was determined using MMRM model with Baseline + HbA1c Stratum at Baseline + Country + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

• The TRIM-D is a participant-reported measure designed to assess the impact of diabetes treatment on individuals' functioning and well-being across different diabetes treatments. The questionnaire includes 28 items grouped into 5 sub-domains: treatment burden, daily life, diabetes management, compliance, and psychological health. Each item is assessed on a 5-point scale, with higher scores indicating better health status. All items were summed to obtain a total raw score, which was transformed to a scale of 0 to 100 to obtain a total score. The total score range is 0-100, with a higher total score indicating better overall health and well-being, while a lower total score indicates worse health or well-being.
• LS mean was determined using MMRM model with Baseline + Country + HbA1c Stratum at Baseline + GLP-1 RA Use at Randomization Flag + SU Use at Randomization Flag + Treatment + Time + Treatment*Time (Type III sum of squares) as variables.

The SF-36v2 is a participant-reported measure designed to assess health status using 36 items across 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, the Physical Component Summary and Mental Component Summary. 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 a standard deviation of 10. Higher scores indicate better levels of function and/or better health. Range cannot be specified in norm-based scores.

The EQ-5D-5L is a multidimensional, health-related, quality-of-life instrument. It includes 5 dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) that are assessed at 5 levels of response (no problems, slight problems, moderate problems, severe problems, and unable to perform or extreme problems). The scores in the 5 dimensions were summarized into a health state index score. A single health-state index value was derived, which ranges from less than 0 (health state equivalent to death, negative values are valued as worse than death) to 1 (perfect health). The EQ VAS rates the participants' perceived health from 0 (the worst imaginable health) to 100 (the best imaginable health). This score provides a composite picture of the respondent's health status.