Table 1.

Differences in changes from baseline ALT and AST with empagliflozin relative to placebo or glimepiride

Trial	ALT (U/l)	AST (U/l)
EMPA-REG OUTCOME®
Adjusted mean (95% CI) difference vs placebo in change from baseline at week 28
All participants	−2.22 (−2.83, −1.62) p < 0.0001	−1.01 (−1.48, −0.54) p < 0.0001
Tertile 3 (highest tertile) by ALT/AST at baseline	−4.36 (−5.51, −3.21) p < 0.0001	−1.53 (−2.35, −0.72) p = 0.0002
Adjusted mean (95% CI) difference vs placebo in change from baseline at week 164
All participants	−1.26 (−2.12, −0.40) p = 0.0040	−0.66 (−1.45, 0.13) p = 0.1007
Tertile 3 (highest tertile) by ALT/AST at baseline	−2.22 (−3.78, −0.66) p = 0.0053	−0.99 (−2.34, 0.36) p = 0.1504
Pooled 24-week placebo-controlled trial data
Adjusted mean (95% CI) difference vs placebo in change from baseline at week 24
All participants	−3.15 (−4.11, −2.18) p < 0.0001	−1.45 (−2.12, −0.78) p < 0.0001
Tertile 3 (highest tertile) by ALT/AST at baseline	−5.60 (−7.41, −3.79) p < 0.0001	−2.84 (−4.14, −1.54) p < 0.0001
EMPA-REG H2H-SU
Adjusted mean (95% CI) difference vs glimepiride in change from baseline at week 28
All participants	−4.88 (−6.68, −3.09) p < 0.0001	−2.78 (−3.92, −1.64) p < 0.0001
Tertile 3 (highest tertile) by ALT/AST at baseline	−7.14 (−10.11, −4.18) p < 0.0001	−3.92 (−5.79, −2.04) p < 0.0001
Adjusted mean (95% CI) difference vs glimepiride in change from baseline at week 104
All participants	−4.28 (−6.11, −2.45) p < 0.0001	−3.00 (−4.33, −1.67) p < 0.0001
Tertile 3 (highest tertile) by ALT/AST at baseline	−6.03 (−9.02, −3.04) p < 0.0001	−5.25 (−7.47, −3.03) p < 0.0001

MMRM analysis in participants treated with at least one dose of study drug based on observed cases, including values after initiation of rescue medication