Mediators of ertugliflozin effects on heart failure and kidney outcomes among patients with type 2 diabetes mellitus

Figures

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  FIGURE 1. Percentage of mediation by biomarkers on hospitalization for heart failure. HR (95% CI) for the unweighted prespecified HHF. †First change from baseline measurement. ‡Weighted average of change from baseline from all post‐baseline measurements. Mediators in blue were associated with decreases in placebo‐adjusted changes from baseline with ertugliflozin; mediators in red were associated with increases in placebo‐adjusted changes from baseline. ALT, alanine aminotransferase; BUN, blood urea nitrogen; eGFR, estimated glomerular filtration rate; HDL‐C, high‐density lipoprotein cholesterol; HHF, hospitalization for heart failure; HR, hazard ratio; SBP, systolic blood pressure; UACR, urine albumin‐to‐creatinine ratio

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  FIGURE 2. Percentage of mediation by biomarkers on a prespecified exploratory kidney composite outcome. HR (95% CI) for the unweighted prespecified exploratory kidney composite outcome comprising sustained 40% decrease from baseline in estimated glomerular filtration rate, chronic kidney replacement therapy, or kidney death was 0.66 (0.50‐0.88). †First change from baseline measurement. ‡Weighted average of change from baseline from all post‐baseline measurements. Mediators in blue were associated with decreases in placebo‐adjusted changes from baseline with ertugliflozin; mediators in red were associated with increases in placebo‐adjusted changes from baseline. HbA1c, glycated haemoglobin; HDL‐C, high‐density lipoprotein cholesterol; HR, hazard ratio; RBC, red blood cell; SBP, systolic blood pressure

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  FIGURE 3. Criteria for mediation and possible mediators for effect of ertugliflozin on HHF and composite renal outcomes. Adapted from Li et al. 20 Copyright © 2020 with permission from Elsevier on behalf of the American College of Cardiology Foundation. ALT, alanine aminotransferase; AST, aspartate aminotransferase; BUN, blood urea nitrogen; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; FPG, fasting plasma glucose; HbA1c, glycated haemoglobin; HDL‐C, high‐density lipoprotein cholesterol; HHF, hospitalization for heart failure; LDL‐C, low‐density lipoprotein cholesterol; RBC, red blood cell; SBP, systolic blood pressure; UACR, urine albumin‐to‐creatinine ratio