Trial Outcomes & Findings for A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (NCT NCT04255433)

A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes

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.

The number of participants from randomization to time to occurrence of Clinical Endpoint Committee (CEC) confirmed all-cause death was reported. Time to event was defined as the number of days from the date of randomization to the first occurrence of all-cause death during the study follow-up period. Participants without an event were censored at their last known contact or end of follow-up.

Number of participants from time of randomization to time to occurrence of CEC confirmed CV death was reported. Time to event was defined as the number of days from the date of randomization to the first occurrence of CV death during the study follow-up period. Participants without an event were censored at their last known contact or end of follow-up.

The number of participants from randomization to first occurrence of CEC confirmed MI was reported. Time to event was defined as the number of days from the date of randomization to the first occurrence of nonfatal MI during the study follow-up period. Participants without an event were censored at their last known contact or end of follow-up.

The number of participants from randomization to first occurrence of CEC confirmed stroke was reported. Time to event was defined as the number of days from the date of randomization to the first occurrence of nonfatal stroke during the study follow-up period. Participants without an event were censored at their last known contact or end of follow-up.

The number of participants from randomization to first occurrence of MACE-4 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.

The number of participants from randomization to first occurrence of Clinical Endpoint Committee (CEC) confirmed heart failure requiring hospitalisation or urgent heart failure 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.

The number of participants from randomization to first occurrence of coronary revascularization was reported. Time to event was defined as the number of days from the date of randomization to the first occurrence of revascularization during the study follow-up period. Participants without an event were censored at their last known contact or end of follow-up.

New or worsening nephropathy (Composite Endpoint 1) was defined as the first occurrence of any of the following events: persistent macroalbuminuria (urine albumin-to-creatinine ratio \>300 mg/g), persistent doubling of serum creatinine with eGFR \<45 mL/min/1.73 m², onset of end-stage renal disease (including initiation of chronic dialysis or kidney transplantation), or death due to renal disease. Time to event was defined as the number of days from the date of randomization to the first occurrence 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.

Change from baseline in eGFR calculated as difference between value at 36 months and baseline value. Participants included in this analysis were classified as having high or very high risk of chronic kidney disease at baseline based on their kidney function (eGFR) and urine albumin-to-creatinine ratio (UACR). High risk included participants with eGFR 45 to less than 60 milliliters/minutes/1.73 square metres (mL/min/1.73 m²) and UACR greater than 30 mg/g, or eGFR 60 mL/min/1.73 m² or higher with UACR greater than 300 mg/g. Very high risk included participants with eGFR less than 45 mL/min/1.73 m² or severely increased UACR (greater than 300 mg/g). These criteria are associated with an increased risk of worsening kidney function. Least squares (LS) mean was calculated using analysis of covariance (ANCOVA) model for endpoint measures: Variable = Baseline + Treatment + Analysis Country + Baseline sodium-glucose cotransporter-2 (SGLT-2) Use Flag.

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Change in HbA1c from baseline up to 36 months during in-trial period were reported. In-trial observation period was defined as the period from date of randomization to the first of (both inclusive): date of follow-up visit, date when participant withdrew consent, date of last contact with participant (for participant lost to follow-up), and date of death. LS mean was calculated using ANCOVA model for endpoint measures: Variable = Baseline + Treatment + Analysis Country + Baseline SGLT-2i Use Flag (Type III sum of squares).

LS mean was calculated using ANCOVA model for endpoint measures: Variable = Baseline + Treatment + Analysis Country + Baseline SGLT-2i Use Flag (Type III sum of squares)

Urine samples were collected for the analysis of UACR. UACR (gram per kilograms \[g/kg\]) was calculated as urine albumin (gram per liter \[g/L\])/urine creatinine (kg/L). Percent change from baseline at 36 months was calculated as: \[(UACR at 36 months - baseline UACR) / baseline UACR\] × 100. LS mean was calculated using ANCOVA model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment + Analysis Country + Baseline SGLT-2i Use Flag (Type III sum of squares).

Blood samples of participants who had fasted for 12 to 14 hours were collected for lipid profile (TC, LDL-C, HDL-C, TG) assessment. The lipid profile asesses the risk of heart disease. Percent change from baseline = 100\*(post-baseline assessment - baseline assessment)/baseline assessment. LS mean was calculated using ANCOVA model for endpoint measures: log(Actual Measurement/Baseline) = log(Baseline) + Treatment + Analysis Country + Baseline SGLT-2i Use Flag.