Analysis . | Risk of MACE with liraglutide vs. placebo, HR (95% CI) . | Percentage mediation (95% CI)† . |
---|---|---|
Total treatment effect (primary LEADER analysis) | 0.868 (0.778; 0.968) | — |
Treatment effect adjusted for: | ||
HbA1c | ||
Change as time-dependent covariate | 0.880 (0.787; 0.984) | 9.9 (−11.4; 59.0) |
Updated mean as time-dependent covariate* | 0.920 (0.820; 1.033) | 41.1 (8.6; 161.0) |
Body weight | ||
Change as time-dependent covariate | 0.860 (0.770; 0.962) | −7.4 (−43.9; 13.3) |
Updated mean as time-dependent covariate* | 0.864 (0.772; 0.968) | −3.9 (−47.0; 26.2) |
UACR | ||
Change as time-dependent covariate | 0.899 (0.804; 1.004) | 21.9 (7.5; 106.4) |
Updated mean as time-dependent covariate* | 0.907 (0.812; 1.013) | 28.6 (12.3; 132.8) |
Confirmed hypoglycemia | ||
Change as time-dependent covariate | 0.868 (0.778; 0.967) | −0.3 (−4.5; 2.2) |
Updated mean as time-dependent covariate* | 0.868 (0.778; 0.968) | −0.1 |
SBP | ||
Change as time-dependent covariate | 0.874 (0.784; 0.975) | 5.2 (−0.6; 21.2) |
Updated mean as time-dependent covariate* | 0.877 (0.787; 0.979) | 7.7 (0.2; 31.7) |
LDL cholesterol | ||
Change as time-dependent covariate | 0.869 (0.778; 0.970) | 0.6 (−4.2; 7.7) |
Updated mean as time-dependent covariate* | 0.869 (0.778; 0.970) | 0.7 (−4.2; 8.8) |
Insulin use | ||
Change as time-dependent covariate | 0.889 (0.796; 0.993) | 16.9 (3.1; 85.7) |
Updated mean as time-dependent covariate* | 0.894 (0.801; 0.998) | 20.7 |
SU use | ||
Change as time-dependent covariate | 0.861 (0.772; 0.960) | −5.6 (−25.2; −0.3) |
Updated mean as time-dependent covariate* | 0.865 (0.776; 0.965) | −2.3 |
Analysis . | Risk of MACE with liraglutide vs. placebo, HR (95% CI) . | Percentage mediation (95% CI)† . |
---|---|---|
Total treatment effect (primary LEADER analysis) | 0.868 (0.778; 0.968) | — |
Treatment effect adjusted for: | ||
HbA1c | ||
Change as time-dependent covariate | 0.880 (0.787; 0.984) | 9.9 (−11.4; 59.0) |
Updated mean as time-dependent covariate* | 0.920 (0.820; 1.033) | 41.1 (8.6; 161.0) |
Body weight | ||
Change as time-dependent covariate | 0.860 (0.770; 0.962) | −7.4 (−43.9; 13.3) |
Updated mean as time-dependent covariate* | 0.864 (0.772; 0.968) | −3.9 (−47.0; 26.2) |
UACR | ||
Change as time-dependent covariate | 0.899 (0.804; 1.004) | 21.9 (7.5; 106.4) |
Updated mean as time-dependent covariate* | 0.907 (0.812; 1.013) | 28.6 (12.3; 132.8) |
Confirmed hypoglycemia | ||
Change as time-dependent covariate | 0.868 (0.778; 0.967) | −0.3 (−4.5; 2.2) |
Updated mean as time-dependent covariate* | 0.868 (0.778; 0.968) | −0.1 |
SBP | ||
Change as time-dependent covariate | 0.874 (0.784; 0.975) | 5.2 (−0.6; 21.2) |
Updated mean as time-dependent covariate* | 0.877 (0.787; 0.979) | 7.7 (0.2; 31.7) |
LDL cholesterol | ||
Change as time-dependent covariate | 0.869 (0.778; 0.970) | 0.6 (−4.2; 7.7) |
Updated mean as time-dependent covariate* | 0.869 (0.778; 0.970) | 0.7 (−4.2; 8.8) |
Insulin use | ||
Change as time-dependent covariate | 0.889 (0.796; 0.993) | 16.9 (3.1; 85.7) |
Updated mean as time-dependent covariate* | 0.894 (0.801; 0.998) | 20.7 |
SU use | ||
Change as time-dependent covariate | 0.861 (0.772; 0.960) | −5.6 (−25.2; −0.3) |
Updated mean as time-dependent covariate* | 0.865 (0.776; 0.965) | −2.3 |
SBP, systolic blood pressure; SU, sulfonylurea.
Calculated as the trapezoidal area under the curve divided by time.
CI for the percentage mediation was estimated using a bootstrap resampling procedure.