If I lose weight on a GLP-1 medication, do I have to be on it forever?
“Forever” feels like a very long time. If you’re thinking about being on a medication for decades, it’s natural to wonder whether that’s realistic. But in medicine, “forever” rarely means permanent. It really just means until the next innovation arrives.
From Twice Daily to Once Weekly
It’s worth remembering that the medications we now think of as “established” haven’t been around forever either. Metformin, the baseline drug for what’s commonly thought to be around “foverever,” was only approved in the United States in 1995. It’s younger than I am.
GLP-1s are just slightly newer, by about 10 years. The first of the class, Exenatide (Byetta), was approved in 2005 and required twice-daily injections. That quickly gave way to Liraglutide (Victoza in 2010, Saxenda in 2014), which reduced the schedule to once daily. Then came Semaglutide (Ozempic in 2017, Wegovy in 2021), which pushed the interval to once weekly.
Most recently, Tirzepatide (Mounjaro in 2022, Zepbound in 2023) has continued that trend. It’s also a once-weekly injection, but with a novel dual GLP-1/GIP mechanism, it has shown greater weight loss and better tolerability than its predecessors.
The trend is unmistakable:
2005 → twice daily (Byetta)
2010 → once daily (Liraglutide)
2017 → once weekly (Semaglutide)
2022 → once weekly, dual mechanism (Tirzepatide)
Every step has meant more convenience and better outcomes.
What’s Next After Weekly Injections?
The next leap forward is already in development.
The most attention is on monthly injections. MariTide, Amgen’s candidate, recently completed a Phase 2 trial showing nearly 20% weight loss at one year, with additional improvements in blood sugar and blood pressure. Its long half-life allows for dosing just once a month, and Phase 3 trials are now underway.
Another contender is MET-097i, a monthly GLP-1 from Metsera. Early studies show sustained double-digit weight loss and a half-life long enough to support true monthly treatment. These medicines could reshape how we think about chronic therapy by cutting injection frequency by 75%.
Beyond monthly dosing, researchers are pushing even further. Fractyl Health’s Rejuva® gene therapy is perhaps the boldest step. Instead of repeated injections, it uses a single targeted delivery to the pancreas to enable the body to produce its own GLP-1 on demand. In animal models, one dose prevented obesity and diabetes long-term. Human trials are expected to begin soon, making the idea of a one-time, potentially curative treatment more than just science fiction.
Other Innovations on the Horizon
While monthly and gene-based therapies are stealing the spotlight, there are other advances worth mentioning:
Oral semaglutide (already approved for diabetes) is expected to be approved for Obesity treatment at a higher dose than currently available
Orforglipron, a small-molecule oral GLP-1 from Lilly, just completed Phase 3 trial ATTAIN-1, also likely to be available in 2026.
CagriSema, a combination of semaglutide and cagrilintide, has produced striking results—over 20% weight loss in trials. Addition of Amylin agonist adds a mechanism of action that is different from what’s currently available.
These add more choice and flexibility, but the most transformative changes may come from monthly therapies and beyond.
What About Safety?
It’s reasonable to ask: can these drugs really be taken for decades?
The reassuring answer is that GLP-1s are not untested anymore. Byetta has been around for 20 years, and Semaglutide now has almost a decade of real-world data. Early worries like pancreatitis or thyroid cancer have shown to be less of a concern than initially thought. New safety signals, including rare eye issues, like NAION, do occasionally arise with ongoing surveillance. Such emerging issues are not ignored but this generally does not change the overall risk vs. benefit analysis.
So, Do You Have to Stay on It Forever?
Obesity is a chronic disease. We know that when you stop treating a chronic disease the problem tends to return head on. But “forever” doesn’t mean one drug, at one dose, for the rest of your life.
Think about how far we’ve come in just 20 years. In 2005, the best option was a twice-daily injection. Today, we have weekly dual-action medicines. By the 2030s, monthly therapies, oral pills, or even gene-based cures may be commonplace.
So the real answer is: you don’t have to take your current medication forever. You only need it until the next breakthrough arrives—and the breakthroughs are coming fast.