Liver Safety of Orforglipron in Adults with Obesity, Overweight, or Type 2 Diabetes: Combined Results from Phase 3 Trials

In a pooled analysis of 11,220 participants, orforglipron treatment was associated with mean reductions in ALT and AST levels.

• Categorical elevations of ALT and AST were generally balanced between orforglipron and comparator treatments.
• Both orforglipron and comparators had an incidence of ALT or AST ≥ 3 × ULN and TBIL ≥ 2 × ULN at 0.1%.
• Alternative causes explained all cases of elevated liver enzymes in orforglipron-treated participants, which did not meet criteria for drug-induced liver injury.
• The incidence of hepatic adverse events was comparable between orforglipron and the pooled comparators.
• Results were consistent among participants with both normal and elevated baseline aminotransferase levels.

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