Danuglipron: The Pfizer Pill That Died
Pfizer’s oral small-molecule GLP-1 receptor agonist, discontinued April 14, 2025, after a single asymptomatic case of drug-induced liver injury surfaced during phase 2 dose-optimization. The story of how a $10B oral GLP-1 program collapsed.
Safety Database
That Killed It
Was Reformulated
How It Works
Non-peptide GLP-1 receptor agonist designed for oral bioavailability without the absorption-enhancer constraints of Rybelsus. Same therapeutic target as Wegovy / Zepbound but in pill form.
Original twice-daily formulation discontinued late 2023 due to high GI side-effect rates and tolerability issues. Pfizer then advanced a once-daily modified-release formulation as the lead asset.
A single asymptomatic case of drug-induced liver injury surfaced in dose-optimization studies. Liver enzymes recovered after discontinuation. Aggregate liver-enzyme rates were within GLP-1 class norms — but with lotiglipron previously killed for similar reasons, Pfizer halted the program.
Announced April 14, 2025. Pfizer redirected its obesity strategy toward an oral GIPR antagonist (different mechanism) currently in phase 2.
What the Data Shows
Key Takeaways
- Discontinued April 14, 2025 by Pfizer — full program halt
- Twice-daily formulation killed earlier (2023) for GI tolerability
- Once-daily lead asset killed for a single confirmed drug-induced liver injury case
- Aggregate liver-enzyme elevation rates were class-typical across 1,400+ patients
- Lotiglipron — a sister Pfizer oral GLP-1 — was killed earlier for similar liver concerns
- Pfizer redirected to an oral GIPR antagonist (phase 2) as alternate obesity bet
- Whether the molecule could have been salvaged with a hepatic safety monitoring plan
- How the danuglipron decision compares to Lilly's orforglipron risk-benefit (orforglipron approved with no liver-specific REMS)
- Whether the GIPR antagonist program will produce a marketable obesity drug
- Real-world phase 3 data — never generated
Frequently Asked Questions
What was danuglipron?
Danuglipron was Pfizer's oral, non-peptide GLP-1 receptor agonist intended for chronic weight management — the company's flagship attempt at a daily oral obesity pill to compete with Wegovy and Zepbound.
Why was danuglipron discontinued?
On April 14, 2025, Pfizer announced discontinuation of the once-daily formulation after a single asymptomatic case of drug-induced liver injury surfaced during dose-optimization studies. Although the participant's liver enzymes recovered after stopping the drug, and aggregate elevation rates across 1,400+ patients were within GLP-1 class norms, the regulatory and reputational risk — combined with the prior loss of a related compound (lotiglipron) for similar reasons — led Pfizer to halt the entire program.
Is danuglipron different from orforglipron?
Yes. Both are oral non-peptide GLP-1 receptor agonists, but they are different molecules from different companies (Pfizer vs Eli Lilly). Orforglipron was FDA-approved as Foundayo on April 1, 2026, with no liver safety REMS — its phase 3 hepatic safety profile cleared the regulatory bar that Pfizer chose not to push danuglipron through.
Can I still get danuglipron?
No. The compound was never FDA-approved and the program is fully halted. There is no path to clinical or commercial supply.
What is Pfizer doing next in obesity?
Pfizer announced a strategic shift to an oral GIPR antagonist (a different obesity mechanism — antagonizing GIP rather than agonizing GLP-1) currently in phase 2 development. They have also explored other earlier-stage obesity assets internally.
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Educational purposes only. Not medical advice.
Danuglipron was never FDA-approved and is no longer in development. This page is historical / informational.