A new daily oral medication, orforglipron, may offer a solution to a common challenge faced by those using GLP-1 drugs for weight loss: keeping the weight off after discontinuing injections.
Clinical Trial Results: In a late-stage clinical trial, participants who switched from weekly injectable GLP-1 medications (Wegovy or Zepbound) to the experimental pill maintained almost all of the weight they had lost over a year. This contrasts sharply with those who switched to a placebo, who regained roughly 20 pounds within six months.
Why This Matters: The difficulty of long-term weight maintenance after stopping GLP-1 injections is well-documented; most people regain significant weight. This new pill addresses a critical unmet need in obesity treatment, offering a more sustainable approach.
The Orforglipron Study: Key Findings
The trial, known as ATTAIN-MAINTAIN, involved nearly 400 adults who had previously lost weight using Wegovy or Zepbound. Participants were re-randomized to receive either orforglipron or a placebo for 52 weeks, alongside continued dietary and exercise guidance. The goal was not further weight loss, but maintenance.
- Wegovy Switchers: Those transitioning from Wegovy to orforglipron regained an average of just 2 pounds after one year.
- Zepbound Switchers: Individuals who switched from Zepbound regained an average of 11 pounds.
- Placebo Group: The placebo group experienced significant weight regain, averaging around 20 pounds.
The Potential Impact: Convenience and Access
The shift to a daily pill could increase the number of people willing to try GLP-1 therapy, particularly those hesitant about long-term injections. According to Dr. Fatima Cody Stanford, an obesity medicine physician-scientist at Harvard Medical School, the convenience factor may reduce barriers related to stigma, storage, travel, and daily logistics.
How it Works: Orforglipron activates the same hormone receptors as injectable GLP-1s, but absorption, activity duration, and metabolism differ. These distinctions can affect dosing, side effects, and adherence.
Regulatory Approval and Availability
Eli Lilly has submitted orforglipron to the FDA for obesity and overweight treatment approval. The drug has received a priority voucher, potentially speeding up the review process. Lilly anticipates approval as early as next year, possibly by March 28.
Competition on the Horizon: Novo Nordisk is also developing a semaglutide pill (the “Wegovy pill”) expected to reach the market even sooner, potentially by late 2024 or early 2025. Orforglipron may be more convenient, as it doesn’t require food restrictions like the semaglutide pill.
Cost and Long-Term Implications
The pills could lower treatment costs, improving access for more people. Lilly has reached an agreement with the U.S. government on pricing: the lowest dose will cost $149 per month, with higher doses reaching $399 through LillyDirect’s self-pay channel.
Evidence suggests that 50-75% of people discontinue GLP-1 injectables within a year. A daily pill may improve long-term adherence, increasing the likelihood of sustained weight loss. This addresses one of the most persistent challenges in obesity treatment today.
In conclusion: Orforglipron and similar oral GLP-1 medications represent a significant advancement in obesity care, offering a more accessible and potentially sustainable solution for long-term weight management. The FDA’s expedited review process suggests these pills could soon become a vital tool in the fight against obesity.
