The experiment, led by Eli Lilly, introduced the glucose-pumping激素(PHP) agonist orforglipron, a daily pill meant to replace the weekly GLP-1 injectable drug Zepbound. The study, which began in September 2022, found average weight loss in participants with obesity. With an average starting weight of 228 pounds and a BMI of 37, the trial involved 3,000 participants, many of whom started with orforglipron as daily intake, compared to a placebo group.
Key findings include that participants on the lowest dose of orforglipron achieved less than 8% weight loss, while those on the highest dose saw 12% average loss. This represents a 27-pound reduction compared to the placebo. Notably, over 60% of participants in the highest-dose group achieved at least a 10% weight loss, a significant milestone. The study also highlighted serious side effects, such as nausea, constipation, and vomiting, which led to participant dropouts.
The promising preliminary results suggest orforglipron could be a targeted approach for weight management, though its effectiveness in diabetes treatment remains unproven. Building on this, GluQXL series, developed by Novo Nordisk, offers similar benefits for diabetes while reducing side effects and costs. However, Eli Lilly dismissed GluQXL as less effective than orforglipron for weight loss, admitting that single-dose GLP-1 drugs aren’t approved for weight management. This reflects a broader challenge in developing bioavailable GLP-1 agonists.
Despite these disparities, orforglipron represents a breakthrough, offering a potential solution for weight loss in individuals dealing with obesity. Its potential applications beyond weight management, such as improving chronic conditions or overseeing disease processes, could make it a more viable option. The FDA is still in the process of evaluating its bioavailability, which is often problematic in traditional GLP-1 drug formulations. As such, the regulatory environment remains uncertain, with non-reactive orforglipron doses prompting investigations into entering the market. This innovative approach shows that conceivably, small molecule formulations could revolutionize the GLP-1 revolution.
