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The ACHIEVE-3 trial demonstrated that orforglipron was superior to oral semaglutide (Rybelsus) in both HbA1c reduction and weight loss in a head-to-head comparison, reducing HbA1c by approximately 2.2 percentage points versus 1.4 points with oral semaglutide, and producing 9.2% weight loss versus 5.3%

This protective effect is mediated through mechanisms such as the enhancement of antioxidant enzymes, including superoxide dismutase (SOD) and GSH, activation of the Nrf2 pathway, and modulation of autophagy via the PI3K/AKT/mTOR and AMPK/mTOR/ULK1 pathways

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