Pfizer’s discontinuation of danuglipron brings the company down to a single molecule in its obesity pipeline.
Pfizer will no longer invest in the development of its oral GLP-1 drug danuglipron after the pharma detected a potential case of drug-induced liver injury, the company announced on Monday.
“Although danuglipron is not Pfizer’s only obesity asset, today’s update sends the company back to the starting block,” BMO Capital Markets wrote in a note Monday morning.
Pfizer maintained that the patient with liver injury, which was detected during dose-optimization studies, was asymptomatic and that the complication “resolved after discontinuation of danuglipron.” The pharma added that in more than 1,400 patients treated so far, the overall occurrence of liver enzyme elevations was “in-line” with other approved therapies in this class.
Still, Pfizer has decided to discontinue danuglipron “after a review of the totality of information, including all clinical data generated to date … and recent input from regulators.”
With the discontinuation of danuglipron, Pfizer is now down to one clinical-stage obesity asset: the oral GIP analog PF-07976016, which is currently in Phase II development. According to a federal clinical trials register, the study has an initial completion date of December 2025.
Like other drugs in its class—such as Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound—danuglipron works by targeting and activating the GLP-1 receptor, in turn promoting the secretion of insulin in response to spikes in blood sugar. Danuglipron also slows the emptying of the stomach, helping to suppress hunger and appetite.
Despite that well-characterized mechanism of action, danuglipron has struggled to prove its value in the clinic. In December 2023, Pfizer announced that it would no longer be testing danuglipron as a twice-daily pill after it saw high rates of side effects in a Phase IIb study. Up to 73% of treated patients experienced nausea, while roughly 47% and 25% developed vomiting and diarrhea, respectively.
Discontinuation as a result of side effects was high, reaching over 50% across all danuglipron doses, Pfizer revealed at the time.
A few months later, in July 2024, the pharma said it had tweaked danuglipron’s formulation and would continue advancing the drug as a once-daily pill. This move brought danuglipron back to Phase I testing, though the setback didn’t seem to shake the pharma’s commitment to weight loss.
At the 2025 J.P. Morgan Healthcare Conference in January, CEO Albert Bourla reiterated that Pfizer would go “all in” on obesity and has even brought in additional experts to help with decision-making, though he tempered investors’ expectations of danuglipron, noting that he is “very cautious” about the asset.
William Blair had an idea for Pfizer. In a Monday morning note, analysts called “Pfizer’s setback . . . an invigorating development for Viking’s shareholders. Specifically, they said, “VK2735 could offer Pfizer a rare opportunity to reestablish not only a mere presence in obesity, but also a leading position beyond” the current Novo Nordisk/Eli Lilly duopoly.
Danuglipron isn’t Pfizer’s first failed weight-loss drug. In June 2023, the company axed lotiglipron, another GLP-1 therapy, which it had been testing for obesity and type 2 diabetes. Lotiglipron was also associated with liver safety issues, particularly elevated levels of transaminases.
