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Table 1 Biochemical measurements that potentially mediated the effect of dulaglutide on MACE-single factor analysis

From: Exploring potential mediators of the cardiovascular benefit of dulaglutide in type 2 diabetes patients in REWIND

  Potential mediators
  HbA1c (%)a Body weight (kg) Systolic BP (mmHg) LDL (mmol/L) UACR (mg/mmol)a WHR in men (m) WHR in women (m)
Baseline value for dulaglutideb 7.3% (1.1) 88.5 (18.4) 137.1 (16.6) 2.56 (0.98) 1.80 (0.70–6.60) 1.02 (0.07) 0.94 (0.07)
Baseline value for placebob 7.4% (1.1) 88.9 (18.6) 137.3 (17.0) 2.56 (0.98) 1.88 (0.70–7.38) 1.02 (0.07) 0.95 (0.07)
LSM change from baseline (CI) − 0.61 (− 0.65, − 0.58)* − 1.50 (− 1.70, − 1.31)* − 1.70 (− 2.07, − 1.33)* − 0.05 (− 0.08, − 0.02)* − 3.05 (− 4.35, − 1.75)* − 0.003 (− 0.006, − 0.000)* − 0.005 (− 0.008, − 0.001)*
HR of updated mean value of variable on MACE 1.087 (1.033, 1.144)* 0.994 (0.983, 1.005) 0.999 (0.995, 1.004) 1.054 (0.958, 1.159) 1.003 (1.002, 1.004)* 1.876 (0.277, 12.721) 2.645 (0.295, 23.742)
 HR of dulaglutide on MACE (after adjusting for the baseline and updated mean value of the variable) 0.923c (0.819, 1.039) 0.889c (0.784, 1.007) 0.880 (0.787, 0.984) 0.937c
(0.811, 1.082)
0.914c
(0.804, 1.039)
0.926c (0.776, 1.104) 0.915c (0.721, 1.160)
 Percentage mediated by updated mean towards the effect of dulaglutide on MACEd 36.1 6.2 − 1.7 48.0 28.5 23.0 45.0
HR of change from baseline value of variable on MACE 1.047 (1.000, 1.008)* 0.998 (0.988, 1.008) 1.000 (0.996, 1.003) 1.064 (0.984, 1.151) 1.002 (1.002, 1.003)* 1.434 (0.310, 6.631) 1.828 (0.296, 11.284)
 HR of dulaglutide on MACE (after adjusting for the baseline and change from baseline value of the variable) 0.900c (0.801, 1.013) 0.896c (0.791, 1.014) 0.880 (0.787, 0.984) 0.937c (0.811, 1.083) 0.910c (0.801, 1.035) 0.925c (0.776, 1.103) 0.913c (0.720, 1.158)
 Percentage mediated by change from baseline toward the effect of dulaglutide on MACEd 16.7 12.3 − 1.5 48.6 25.4 22.3 44.2
  1. BP blood pressure, CI confidence interval, HR hazard ratio, IQR interquartile rate, LDL low density lipoprotein, LSM least squares mean, MACE major adverse cardiovascular event, SD standard deviation, UACR urine albumin/creatinine ratio, WHR waist-to-hip ratio
  2. aVariables that satisfy all 3 conditions to be a mediator
  3. bThe value is presented in mean (SD) or in median (IQR)
  4. cThe estimated HR less than the HR for the unadjusted model
  5. dCompared to the previously reported HR of dulaglutide vs placebo on MACE of 0.882 (95% CI 0.789, 0.985) except for WHR (men) was compared with HR of dulaglutide on MACE for male subgroup of 0.905 (95%CI 0.787,1.040) and WHR (women) was compared with HR of dulaglutide on MACE for female subgroup of 0.850 (95% CI 0.709,1.020); *p-value < 0.05