Core Viewpoint - Eli Lilly's oral GLP-1 therapy orforglipron has demonstrated superior efficacy in treating type 2 diabetes compared to AstraZeneca's SGLT2 inhibitor Farxiga, achieving significant reductions in A1C levels and weight loss in recent trials [2][4]. Group 1: Clinical Trial Results - In the latest Phase III trial ACHIEVE-2, orforglipron was tested on 962 adult participants with type 2 diabetes who had inadequate blood sugar control after metformin. The study compared three doses of orforglipron against Farxiga, with the primary goal of demonstrating non-inferiority in A1C reduction after 40 weeks [2][4]. - All doses of orforglipron met the primary and all key secondary endpoints, significantly lowering A1C levels and promoting weight loss. Specifically, the 3 mg dose resulted in a 1.3% reduction in A1C, while the 12 mg and 36 mg doses achieved a 1.7% reduction. In contrast, Farxiga only resulted in a 0.8% reduction [4]. - Another late-stage study, ACHIEVE-5, also showed positive results for orforglipron compared to placebo in patients with insufficient blood sugar control who were using titrated insulin glargine. The 3 mg dose led to a 1.5% reduction in A1C, the 12 mg dose achieved a 2.1% reduction, and the 36 mg dose resulted in a 1.9% reduction, while placebo only saw a 0.8% reduction [4]. Group 2: Safety and Tolerability - The safety and tolerability of orforglipron in both studies were consistent with previous findings, with stable discontinuation rates. The most common adverse reactions were gastrointestinal symptoms, which were generally mild to moderate, and no liver safety issues were observed [4]. Group 3: Future Developments - Detailed data from the two studies will be presented at an upcoming medical conference. The final global registration study of the ACHIEVE program, ACHIEVE-4, is expected to be completed in the first quarter of 2026, paving the way for orforglipron's market application in type 2 diabetes [5]. - Additionally, the application for orforglipron's use in obesity treatment is set to be initiated by the end of this year [6].