Lilly(US:LLY) GLP1减重宝典·2025-06-27 08:36Core Viewpoint - GLP-1 class drugs are becoming a significant treatment direction in the fields of glycemic control and weight loss, with Orforglipron emerging as a promising oral non-peptide small molecule GLP-1 receptor agonist that offers convenience and efficacy [1][3][13] Summary by Sections Introduction to GLP-1 Drugs - Current GLP-1 therapies primarily use peptide structures requiring subcutaneous injection, which is inconvenient for patients [1] Orforglipron Overview - Orforglipron is a non-peptide small molecule GLP-1 receptor agonist with high oral bioavailability, allowing for administration without dietary or drinking restrictions [3] - It was recognized in 2023 as a notable small molecule in the "Hunter of Drugs" annual list due to its technological path, scientific value, clinical prospects, and innovation [3] Clinical Trial Results - The ACHIEVE-1 trial, a phase 3 study, included 559 adults with early-stage type 2 diabetes, assessing three doses of Orforglipron (3 mg, 12 mg, 36 mg) over 40 weeks [4] - The trial demonstrated significant improvements in HbA1c levels, with 68% to 73% of patients achieving treatment goals (HbA1c < 7.0%) [3][5] Efficacy Results - At week 40, all Orforglipron treatment groups showed significantly better glycemic control compared to the placebo group (P<0.001) [5] - HbA1c reductions were as follows: 3 mg group -1.24%, 12 mg group -1.47%, 36 mg group -1.48%, while the placebo group saw a reduction of only -0.41% [5] Blood Sugar Control Performance - Orforglipron groups showed superior results in achieving various HbA1c targets compared to the placebo group [6] - Notably, 17%-24% of Orforglipron patients reached HbA1c ≤ 5.7%, compared to only 4% in the placebo group [6] Weight Loss and Metabolic Improvement - Orforglipron demonstrated dose-dependent weight loss: 3 mg group -4.5% (4.2 kg), 12 mg group -5.8% (5.2 kg), 36 mg group -7.6% (7.2 kg) [8] - In comparison, the placebo group lost only 1.7% (1.5 kg) [8] - The proportion of patients achieving weight loss ≥5% was 43%-61% in the Orforglipron groups versus 17% in the placebo group [9] Lipid Regulation - Orforglipron also showed positive effects on lipid levels, particularly in the 36 mg group, with significant reductions in triglycerides and non-HDL cholesterol [11] Safety Observations - The most common adverse effects were mild to moderate gastrointestinal discomfort, primarily during dose escalation, with no serious hypoglycemic events reported [12] Conclusion and Outlook - Orforglipron presents a promising option for type 2 diabetes patients who struggle to achieve glycemic control through lifestyle changes alone, offering a convenient oral administration method that enhances blood sugar management, weight control, and metabolic parameters [13]