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Pfizer Takes On Eli Lilly & Novo: Who Gets OUTPLAYED in the Obesity Arms Race?

Pfizer just released mid-stage data from its Metsera-acquired obesity drug showing 12.3% weight loss at 28 weeks with monthly dosing. It’s the company’s first real swing at the obesity market after acquiring Metsera for $10 billion to diversify beyond fading COVID revenues.

The headline efficacy looks decent but not industry-leading — and that’s exactly what the market is focused on. What matters more is how the timeline, design, and dosing frequency compare with entrenched rivals like Lilly and Novo, and where Pfizer may still carve out a lane.

Efficacy Vs. Market Leaders

In VESPER-3, Pfizer’s GLP-1 candidate ‘3944 delivered 12.3% placebo-adjusted weight loss at 28 weeks on a monthly regimen, after starting with weekly dosing. That trails Eli Lilly’s Zepbound and Novo Nordisk’s Wegovy on efficacy, but direct comparisons are limited by trial length and patient differences. Lilly’s 22% weight loss figure came from longer studies, and Pfizer believes a higher monthly dose could push results closer to that threshold.

The Street is discounting the short-term efficacy gap, but the trial isn’t over — and the weight loss curve hasn’t flattened. The broader question is whether Pfizer’s monthly format, if tolerability holds, can unlock persistence advantages and switching opportunities from weekly injections as the market matures…

And that matters if long-term convenience begins to outweigh early efficacy. But even if the dosing format gains traction, the real challenge will be convincing physicians and patients to switch from drugs they already know are effective.

While Pfizer has outlined plans to test a 9.6mg monthly dose in future trials, its leading GLP-1 remains in Phase II and is at least two years behind Lilly and Novo. Analysts expect Pfizer to lean heavily on combination studies and higher-dose maintenance regimens to close the gap. Until then, headline efficacy will remain the reference point — and Pfizer’s drug, for now, still lags on that metric.

Dosing Convenience & Adherence

Pfizer’s decision to pursue monthly injections instead of weekly shots reflects both strategic differentiation and consumer insights. Patients in the VESPER-3 trial started on weekly dosing, then switched to monthly after 12 weeks — and still showed steady weight loss. That’s unusual in the current GLP-1 market, where drugs like Wegovy and Zepbound rely on strict weekly adherence to deliver consistent results.

Monthly dosing could be a key selling point if real-world adherence issues begin to dent outcomes for competitors. Lilly and Novo’s injectables work well when taken consistently, but that’s not always how patients behave. Monthly formats may offer easier compliance and appeal to consumers with busy lifestyles — particularly if they are switching from weekly regimens due to burnout or side effects.

The bigger question is whether monthly shots can gain insurance traction or establish out-of-pocket momentum. Pfizer will likely need to price aggressively or offer consumer incentives through its direct-to-patient portal, PfizerForAll. Novo and Lilly have already set expectations with $199 and $399 cash-pay caps, respectively. The market may not reward a convenience-only strategy unless efficacy keeps up.

Pipeline Depth & Combinations

What makes Lilly and Novo so dominant isn’t just their lead drugs — it’s the depth of their pipelines. Novo’s CagriSema, a combination of cagrilintide and semaglutide, just outperformed Wegovy in a diabetes trial, delivering 14.2% weight loss over 68 weeks. Meanwhile, Lilly’s Zepbound continues to lead on efficacy, and its orforglipron pill could hit the market by mid-year.

Pfizer doesn’t yet have a next-gen combo, but it has flagged interest in stacking GLP-1 with other targets to improve tolerability and durability. Analysts expect combo data later this year, likely after the company progresses ‘3944 through its Phase III studies. Until then, it’s a one-horse race with a mid-pack runner — and no oral contender in sight.

The real risk is falling into a catch-up loop. Pfizer’s delayed entry means it may be launching into a market that’s already pivoting to combinations and pills. If Metsera’s molecules can’t leapfrog current options or pair well with others, Pfizer may need to buy again just to stay relevant.

Commercial Execution In A Crowded Market

Pfizer has distribution muscle and a direct-to-consumer platform with 25 million users. That gives it a head start in reaching patients, but it still faces an uphill climb against brands with stronger clinical momentum and better name recognition. Novo and Lilly already dominate the cash-pay market and have optimized their web stores for repeat orders.

The biggest threat might not be each other — it’s the wave of copycats and compounders offering GLP-1s at lower prices. Pfizer will need a clear reimbursement strategy, along with payor access and co-pay programs, to avoid being boxed out of covered lives. Even with monthly dosing, uptake will hinge on affordability.

Consumer behavior is also shifting. Many are bypassing insurance entirely and shopping directly. Pfizer will need to build trust with this audience, which has already been conditioned by Zepbound and Wegovy. Unless the company can communicate a distinct benefit — whether that’s fewer side effects, better adherence, or lower hassle — it risks being seen as just another entrant in an increasingly commoditized space.

Final Thoughts: A Catch-Up Game With Little Room for Error

Pfizer’s entrance into the weight-loss market comes with promise but also complexity. Its monthly GLP-1 candidate shows early signs of efficacy and differentiation, but trails Lilly and Novo in development timeline, data maturity, and commercial traction. The broader pipeline picture remains thin for now, and competition is shifting toward oral pills and combination therapies.

Yet Pfizer doesn’t need to win the category — it only needs a viable position. With strong cash flow, an established DTC channel, and a consumer market still expanding, a monthly offering may find its niche. Investors looking for dominant share may be disappointed, but those betting on market breadth have reasons to watch.

At 3.1x LTM EV/revenue and under 19x LTM earnings, Pfizer trades at a noticeable discount to the broader obesity cohort. That multiple could re-rate — but only if the next wave of trials starts to close the gap.

Disclaimer: We do not hold any positions in the above stock(s). Read our full disclaimer here.

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