Several weight loss medications are currently on the market that don't require an injection. However, they aren't as widely available, and data is limited to show they're as effective as popular injectable medications. But that all could be changing, as pharmaceutical company Eli Lilly announced today that their oral GLP-1 pill, orforglipron, works just as well for diabetes management and weight loss as the drug Ozempic.
RELATED: Researchers Say This Popular Weight-Loss Drug Can Keep You Slim for 3 Years and Counting.
What is orforglipron?
To have a clear grasp of this new weight-loss pill, it's important to first understand the mechanisms of common injectable drugs.
Eli Lilly manufactures tirzepatide, which is prescribed under the brand names Mounjaro (approved for diabetes) and Zepbound (approved for weight loss).
Novo Nordisk manufactures semaglutide, which is prescribed under the brand names Ozempic (approved for diabetes) and Wegovy (approved for weight loss).
(It should be noted that Mounjaro and Ozempic are commonly taken off-label for weight loss.)
All four of these drugs are Glucagon-like peptide-1 (GLP-1) receptor agonists, which "mimic the way a hormone called glucagon-like peptide 1 works in the body," according to Mayo Clinic.
"When blood sugar starts to rise after a person eats, these medicines cause the body to make more insulin. The extra insulin helps lower blood sugar," they explain.
In terms of weight loss, the medications cause the stomach to empty more slowly and increase how full you feel after eating. "GLP-1 affects areas of your brain that [process] hunger and satiety," notes Cleveland Clinic.
Like these medications, orforglipron is a peptide drug. As The New York Times explains, peptides are small fragments of proteins digested by the stomach.
"So, in order to make an oral GLP-1, chemists had to find a way to make a nonpeptide that acts exactly like a peptide," shares the Times. "The solution was to find a small molecule—thousandths of the size of a peptide—that sinks into a tiny pocket in the protein that is the target for GLP-1s. When it sinks into the pocket, the protein changes shape just as it does when a GLP-1 binds to the whole protein."
Daniel Skovronsky, MD, PhD, Lilly’s chief scientific officer, told the newspaper that this discovery was "the holy grail."
Orforglipron is notable because it can be taken any time of day without food or water restraints. While injectables are taken once a week, this would be a once-daily pill.
RELATED: Why Up to 75% of People on Weight-Loss Drugs Stop Taking Them, Cardiologist Says.
How does orforglipron compare to drugs like Ozempic?
Eli Lilly's announcement comes after a successful Phase 3 trial that involved 559 people with type 2 diabetes who took either orforglipron or a placebo for 40 weeks. Results show that orforglipron:
- Lowered A1C (blood sugar) levels by an average of 1.3 to 1.6 percent, "about the same amount in that time period experienced by patients taking Ozempic and Mounjaro in unrelated trials," notes the Times
- Dropped A1C levels into the normal range for 65 percent of users
- Reduced body weight by an average of 7.9 percent (16 pounds) without patients hitting a plateau, "similar to that achieved in 40 weeks with Ozempic but slightly less than with Mounjaro in unrelated trials," says the Times
Eli Lilly is also running a separate trial to understand how orforglipron works in people without diabetes but with obesity. Results of a phase 2 clinical trial were released in June 2023 and showed that orforglipron:
- Reduced body weight by an average of 9.4 to 14.7 percent after 36 weeks
- Improved weight-related and cardiometabolic measures, including systolic blood pressure and total cholesterol
When could this weight-loss pill become available?
Eli Lilly says it hopes to gain approval from the Food & Drug Administration (FDA) later this year to market orforglipron for obesity and in early 2026 for diabetes.
Not only would this make the drug available to people who can't or won't give themselves injections, but experts say a pill will be cheaper to manufacture and distribute, resulting in more affordability for patients.
In fact, Skovronsky told The New York Times that even before today's announcement, Eli Lilly had established factories to manufacture orforglipron and already has a billion pills at the ready.
"As a convenient once-daily pill, orforglipron may provide a new option and, if approved, could be readily manufactured and launched at scale for use by people around the world," concluded David Ricks, Eli Lilly’s CEO.
RELATED: Scientists Say Ozempic Could Have Anti-Aging Powers, Too—Here's What to Know.
What about Rybelsus?
You may have already heard of Rybelsus, the brand name for Novo Nordisk's oral form of semaglutide. This pill is currently approved by the FDA only for the treatment of type 2 diabetes.
However, the main drawback of Rybelsus is that, unlike orforglipron, it still contains the GLP-1 peptide, "so it must be taken in large doses and is not as effective as the injectables because most of it is digested," explains the Times.
The higher dosage could also cause more gastrointestinal side effects, as Best Lifepreviously reported.
