The ACHIEVE-1 trial showed A1C reductions between 1.3% and 1.6% across doses, compared to 0.1% with placebo. From your perspective, how clinically meaningful are these changes in routine diabetes care, especially for patients managed without prior pharmacologic therapy?

Participants on the highest orforglipron dose lost an average of 16 lbs (7.9%) by Week 40, without reaching a weight plateau. How important is this dual impact—on both glycemic control and weight—for modifying the long-term cardiometabolic risk in type 2 diabetes?

The safety and tolerability profile of orforglipron was noted as consistent with injectable GLP-1s. What are the key considerations in comparing oral and injectable GLP-1 therapies, particularly in terms of patient adherence, GI side effects, and real-world implementation?

ACHIEVE-1 used a fixed step-wise titration to reach final doses of 3, 12, or 36 mg. How do you view this structured titration design in terms of clinical practicality, and what does it suggest about dose personalization in future prescribing practices?

Discontinuation due to adverse events was under 10% across doses, despite relatively high rates of GI side effects. What does this say about tolerability thresholds in patients, and how should clinicians manage expectations around early adverse events?

Orforglipron does not require food or water timing restrictions, unlike some oral GLP-1s in development. How relevant is this feature in terms of patient convenience, and could it influence physician prescribing behavior or guideline recommendations?

ACHIEVE-1 focused on treatment-naïve adults with diet- and exercise-controlled type 2 diabetes. What opportunities or challenges do you foresee in positioning orforglipron earlier in the treatment algorithm, potentially ahead of metformin in some populations?

With Lilly projecting global scalability and no supply constraints, what impact could orforglipron have on the accessibility of GLP-1 therapies, particularly in regions where injectables pose logistical or economic challenges?