Lilly Claims Victory Over Novo’s Oral Semaglutide: Here’s What That Really Means
- Jennifer Hardy
- Sep 20
- 6 min read
You may have seen the headlines about Eli Lilly’s orforglipron outperforming Novo Nordisk’s oral semaglutide. On the surface, it sounds like a clean, head-to-head victory. But these kinds of trials aren’t always apples to apples.
One of the goals of GLP-1 Newsroom is to help you cut through press release hype, read between the lines, and understand what these results actually mean before shaping expectations or decisions.
The headline of the Eli Lilly News Release stated, "Lilly's oral GLP-1, orforglipron, superior to oral semaglutide in head-to-head trial." However, we need to explore the context of that statement.
Now, full disclosure, I take Zepbound (tirzepatide), an Eli Lilly dual agonist. However, I pay out of pocket and have no incentive from Lilly (or Novo Nordisk) to report anything other than the truth and my perspective on stories, backed by more than two decades as a journalist.
Why Oral GLP-1s Matter
Up until now, almost every GLP-1 medication making headlines for weight management has come in an injectable pen or vials. That includes Novo Nordisk’s Ozempic and Wegovy, and Lilly’s Mounjaro and Zepbound. Both major players have been racing to develop oral versions, knowing that pills could change the game for patients and prescribers.
As of September 2025, here's where the oral GLP-1 race stands.
Novo Nordisk: Oral semaglutide (Rybelsus) is FDA-approved for type 2 diabetes in 7 mg and 14 mg doses. Higher doses (25 mg and 50 mg), often described as “Wegovy in a pill” or "oral Wegovy", are under FDA review for obesity.
Eli Lilly: Orforglipron (OR-for-GLI-pron) is a once-daily, oral GLP-1 receptor agonist that doesn’t require fasting. Orforglipron is still in late-stage clinical trials but has shown strong results in lowering blood sugar and reducing weight.
It is not tirzepatide in pill form. It’s a completely different molecule, but it’s developed by the same company that makes tirzepatide (Zepbound/Mounjaro).
Since oral Wegovy made it to the FDA for approval first, there's a chance this will be approved by late 2025. Orforglipron is expected to be not too far behind, possibly available in early 2026 if all goes well.
Oral GLP-1s could expand access by removing the injection barrier and potentially lowering costs, though “affordable” in this category is relative. Even current prescriptions can top $1,000 a month, raising questions about how broadly these drugs will be available in practice.
Differences and Similarities of Oral Wegovy vs Oforglipron
I want to dig a little deeper into the difference between the two oral drugs making headlines. It's important because even though Novo Nordisk is known for semaglutide (GLP-1 agonist) and Eli Lilly is known for tirzepatide (a dual agonist, GLP-1 and GIP), Eli Lilly is NOT making an oral version of tirzepatide.
It’s worth noting that while both companies are racing to deliver oral GLP-1 agonists, their products aren’t the same. Oral semaglutide is a peptide that needs an absorption enhancer to work as a pill. Orforglipron is a small molecule, designed from the start to bypass those absorption hurdles that keep most GLP-1s in injectable form.
Both drugs make it past the stomach, but they do it in very different ways. Oral semaglutide relies on an absorption enhancer and strict dosing rules to survive digestion, while orforglipron’s small-molecule design is built to handle stomach acid on its own.
The New Oral GLP-1 Study Released September 2025
In September 2025, Lilly released new data from its ACHIEVE-3 trial. This was the first real head-to-head test of its pill, orforglipron, against Novo’s oral semaglutide (Rybelsus). The trial included 1,698 adults with type 2 diabetes who were already on metformin.
Patients were split into four groups: two doses of orforglipron (12 mg and 36 mg) and two doses of oral semaglutide (7 mg and 14 mg). Everyone stayed on treatment for a full year.
Here is what Lilly reported:
Blood sugar: A1C dropped by about 1.9% on 12 mg orforglipron and 2.2% on 36 mg. Semaglutide saw smaller reductions at 1.1% and 1.4% for its two doses.
Weight: Orforglipron users lost an average of 14.6 pounds (6.7%) on the lower dose and 19.7 pounds (9.2%) on the higher dose. Semaglutide patients lost 7.9 pounds (3.7%) and 11 pounds (5.3%).
Dropouts: More patients stopped orforglipron, around 9 to 10 percent, compared to 4 to 5 percent on semaglutide. Most left due to stomach-related side effects. Reported issues were typical for GLP-1 drugs, such as nausea and diarrhea. No new major safety concerns were reported.
Lilly calls orforglipron a small-molecule GLP-1, meaning it is a pill built to survive digestion. That differs from peptide-based semaglutide, which needs an absorption enhancer and strict fasting rules. Lilly expects to file for FDA approval in 2026 after it completes related obesity trials.
Now, read that again to soak it all in. We're going to give some context in the next section.
Putting the Oral GLP-1 Results in Context
On the surface, ACHIEVE-3 looks like a clean win for Lilly. Orforglipron outperformed oral semaglutide on both blood sugar and weight loss. But there are a few details worth paying attention to before calling this a knockout.
First, this wasn't an apples-to-apples comparison. This study pitted oral semaglutide at 7 mg and 14 mg, approved for type 2 diabetes, not the higher 25 mg or 50 mg versions that Novo is testing for obesity. Looking back at the data, we see Lilly paired it against the 12mg and 36 mg versions of orforglipron. So while Lilly’s pill looks stronger here, we cannot assume the same gap will hold against those higher doses.
Second, ACHIEVE-3 only looked at people with type 2 diabetes who were already taking metformin but still needed better control. That means the findings don’t necessarily apply to patients who aren’t on metformin, or to those using these drugs as first-line therapy. Until we see data in broader populations, the results should be read as specific to that group. However, the word "metformin" was only used twice in the Lilly news release.
Third, the study was open-label. Everyone knew which pill they were taking. That is less of a concern for hard lab numbers like A1C, but it still matters for things like adherence, tolerability, and weight tracking. The gold standard to get the FDA nod is still a randomized, double-blind, placebo-controlled trial whenever possible. At the same time, there's nothing shady about an open-label. It just opens the door for more subtle forms of bias, like people reporting side effects differently or sticking with the drug longer because they believe it’s the ‘better’ option.
It's important that we, as GLP-1 users or potential users, know the distinction when these types of studies are released. Lilly claiming a "superior" product to Novo would be the same as the dairy association touting a study that says milk is good for you. You have to question the source and wording.
Also worth pointing out: the results of this study were going to see daylight no matter what. Because it was registered on ClinicalTrials.gov, Lilly is required to post the outcome, whether flattering or not. What would have changed is the packaging.
If orforglipron hadn’t looked stronger, you probably wouldn’t have seen a polished press release and splashy headlines. Instead, Novo would have been the one seizing the moment, spinning the same line Lilly is pushing now: “our pill looks better than theirs in their own study."
Conclusion: Finding Truth in the Noise
It’s also worth pointing out: this study had nothing to do with obesity or weight-management approvals. ACHIEVE-3 was designed around blood sugar control in people with type 2 diabetes already on metformin. So if you’re looking at these results and thinking about oral GLP-1s for weight loss, this trial doesn’t give you that answer. For obesity, Lilly’s parallel ATTAIN program is where the relevant data will come from.
If you want to read the full release and trial record yourself, here are the links for transparency:
In an era where a headline can become “fact” within minutes on social media, we have to be more vigilant than ever. That means checking the source, reading between the lines, and understanding the difference between marketing spin and scientific truth.
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