Move Over Retatrutide, Protagonist Just Became Your Antagonist

You love to see competition!

A new name just joined the obesity‑drug race and this one is not messing around.

Protagonist Therapeutics just announced PN 477 as its next obesity drug candidate. And no, this is not just another GLP 1. PN 477 is a triple‑agonist peptide that activates GLP 1, GIP, and glucagon receptors with plans for both an oral version (PN 477o) and a once‑weekly injection (PN 477sc).

Here’s what we know:

• PN 477o is a once‑daily pill

• PN 477sc is a once‑weekly injectable

• The oral version was engineered to survive digestion while targeting all three receptors in a balanced way

• Early animal data looks promising for weight loss, blood sugar control, and preserving lean mass

• Phase 1 human trials are expected to begin in the second quarter of 2026

Why this matters:

We’re still waiting for a truly effective oral triple agonist. Lilly’s orforglipron is leading on the oral GLP‑1 front, and Viking’s VK2735 is in the mix—but none offer a triple‑combo pill like PN 477o.

However, Lilly is on track to go first‑to‑market with a subcutaneous triple agonist, retatrutide, expected to launch in early to mid‑2027. In a phase 2 trial, retatrutide showed up to 24% weight loss at 48 weeks earning nicknames like the “King Kong” of weight‑loss drugs. Scores of research grade peptide users are already buying knock-off versions of retatrutide online and using it with remarkable success, though it’s use is not condoned by On The Pen.

So here’s the battlefield:

• Lilly’s retatrutide (SC injection) hits market sometime in 2027 likely with an average of around 24% weight loss

• Protagonist’s PN 477o could be the first oral triple agonist, with Phase 1 starting Q2 2026

• PN 477sc is also poised as a weekly SC injection, likely adding increased potency

If PN 477o delivers Zepbound‑level results in a pill, it could disrupt the landscape, especially for people who prefer oral medications or are sensitive to GI effects.

Who is Protagonist?

They’re a clinical‑stage (meaning their medicines are all still in clinical trials) biotech in California with two peptides in Phase 3 trials one with J&J for psoriasis, the other with Takeda for polycythemia vera. PN 477 is their next solo shot at blockbuster obesity therapy.

What Next?

We’re entering the next wave of obesity treatment. Lilly is aiming to lead with the first SC triple agonist by mid‑2027, but Protagonist is chasing with potentially the first oral triple combo. The race is heating up. And you can be assured the research grade community is already foaming at the mouth to get their hands on it! But seriously, you might want to get that foaming at the mouth checked out, those research peps can be sketchy!

I do think some of the hype around orals are a bit overblown. I love taking a shot, something about it makes me feel…. Alive… Would you be interested in switching to a daily pill if it worked just as well as the weekly shots? Let’s talk.

Stay tuned to OnThePen.com for more updates and in‑depth analysis on the latest developments in weight loss and diabetes treatments. Sharing this article is a powerful form of advocacy that brings us closer to educating the masses and reducing stigma. If you found this insightful, please share it in GLP‑1 and diabetes forums. Together we’re building something special.