Accepted answer
Start with the pattern. A hepatocellular pattern with alanine aminotransferase above aspartate aminotransferase points one way; a cholestatic pattern with alkaline phosphatase and gamma-glutamyl transferase points another.
Hy's law describes the combination that matters: transaminases above three times the upper limit together with bilirubin above twice the upper limit and no cholestatic explanation. That combination is a signal; isolated mild transaminase elevation is not.
Headline results, principal programmes
| Trial | Agent | n | Duration | Primary result |
|---|
| STEP 1 | Semaglutide 2.4 mg | 1,961 | 68 wk | −14.9 % vs −2.4 % weight |
| STEP 2 | Semaglutide 2.4 mg, T2DM | 1,210 | 68 wk | −9.6 % vs −3.4 % weight |
| SURMOUNT-1 | Tirzepatide 5/10/15 mg | 2,539 | 72 wk | −15 / −19 / −21 % weight |
| SURMOUNT-4 | Tirzepatide, withdrawal | 670 | 88 wk | Continued loss vs substantial regain |
| SELECT | Semaglutide 2.4 mg | 17,604 | ~40 mo | MACE HR 0.80 (0.72–0.90) |
| FLOW | Semaglutide 1.0 mg, CKD | 3,533 | ~3.4 yr | Renal composite reduced; stopped early |
| SURMOUNT-OSA | Tirzepatide, OSA | 469 | 52 wk | AHI reduced with and without PAP |
The underlying point is that an isolated result three weeks after starting anything is difficult to interpret. A baseline taken before starting makes the same result trivially interpretable, which is the argument for baselines.
Trials in this class have generally reported improvement rather than deterioration in liver biochemistry, consistent with the weight-mediated mechanism.
Attributing an enzyme change to a compound requires a baseline, and most people asking have not got one.
Read the pattern before the magnitude, and the magnitude in multiples of the upper limit.