Once-a-month shot delivers meaningful weight loss, but Wall Street remains uneasy about competition, tolerability and timing.
Pfizer’s obesity moment finally arrives… just not the way markets hoped. For the multinational pharma-biotech, the latest data on its experimental obesity drug PF’3944 was supposed to be a turning point. After years of stalled internal programs and a costly $10 billion acquisition of biotech Metsera, the company finally had something tangible to show: people on its drug lost substantially more weight than those on placebo, even after switching from weekly injections to just one shot a month [1].
Yet as the science moved forward, the stock moved in the opposite direction. Pfizer shares fell as much as 5% on the day the data dropped, a reminder that in today’s obesity gold rush, “promising” no longer guarantees applause [2].
The Phase 2b VESPER-3 study followed 268 adults with obesity or overweight who did not have type 2 diabetes. Everyone started cautiously, building up the dose over 12 weeks with weekly injections, much like easing into a new workout routine to avoid injury. After that, participants transitioned to monthly maintenance shots.
By week 28, those who completed treatment had lost up to 12.3 percentage points more of their body weight than people given a placebo. Even when counting everyone, including those who dropped out early, the advantage remained meaningful, at up to 11 percentage points.
Crucially, weight loss didn’t stall after the switch to monthly dosing. There was no plateau at 28 weeks, suggesting the drug hadn’t yet reached its full effect. For a class of drugs where momentum often fades over time, that detail stood out.
Now, why did investors still flinch? Despite the encouraging numbers, markets quickly turned comparative. Analysts noted that PF’3944’s performance looks “slightly inferior” to Eli Lilly’s Zepbound at similar points in development, even if direct comparisons between trials are far from exact [2].
There were also questions about tolerability. About 10% of participants receiving PF’3944 discontinued due to side effects, mostly nausea or vomiting, higher than what Lilly has reported in late-stage trials of its highest dose. Pfizer executives emphasized that side effects were mostly mild or moderate and did not spike when patients moved from weekly to monthly dosing.
Still, in an obesity market increasingly defined by razor-thin margins between blockbuster therapies, any hint of friction can spook investors.
Why Pfizer is pushing ahead anyway
On an analyst call, Pfizer’s chief scientific officer Chris Boshoff said the results “increase significantly our confidence” as the company prepares for Phase 3 trials. Those studies, expected to begin later this year, will test a dose twice as high as the strongest one used in Phase 2 [2].
That confidence is not just scientific, but strategic. Pfizer believes PF’3944’s biggest advantage may not be peak weight loss, but convenience. A drug that requires only monthly maintenance dosing could help people stay on treatment longer, a persistent challenge for existing GLP-1 therapies.
From a real-world perspective, fewer injections mean fewer reminders that someone is “on a drug” and potentially fewer dropouts over years of use.
We are recognizing that monthly dosing is not a magic bullet. Other major players, including Amgen, are also exploring longer-acting weight loss drugs. And convenience alone won’t overcome inferior efficacy or side effects if patients and physicians have better options.
But the obesity conversation is quietly shifting. The goal is no longer rapid weight loss at any cost; it’s sustained metabolic health. That’s where PF’3944 fits into a broader longevity narrative.
Obesity accelerates aging by straining the heart, joints and immune system, and by increasing the risk of dozens of chronic conditions. A therapy that people can realistically stay on for years, not months, has implications that extend far beyond the scale.
PF’3944 raises an important question: can obesity drugs evolve into long-term healthspan tools rather than short-term fixes? Monthly dosing hints at that possibility. If patients are more likely to adhere to treatment, they may experience steadier metabolic control, reduced cardiovascular risk and potentially better functional aging outcomes. The trade-off, however, is that long-term use magnifies concerns about tolerability, muscle loss and access. These are issues the next generation of trials will need to address head-on.
Pfizer knows it is late to the party. But it is betting that a different rhythm – slower, steadier and easier to live with – can still carve out space in a crowded market. For now, PF’3944 sits in an uncomfortable middle ground. The science is encouraging. The strategy is defensible. But investors want certainty in a market that has little patience for second place.
Whether Pfizer’s monthly shot can mature from “promising” into “essential” may ultimately determine not just the success of a single drug, but the company’s relevance in the future of obesity and longevity care.
[1] https://www.pfizer.com/news/press-release/press-release-detail/pfizers-ultra-long-acting-injectable-glp-1-ra-shows-robust
[2] https://www.biopharmadive.com/news/pfizer-obesity-metsera-phase-2-results-GLP1-monthly-shot/811201/
