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Zepbound’s Triumph: How Eli Lilly’s Weight Loss Star Could Outshine Novo Nordisk’s Wegovy

Henry RiversSunday, May 11, 2025 6:20 pm ET

28min read

The pharmaceutical industry’s battle for dominance in the weight loss market just got hotter. In a head-to-head trial, Eli Lilly’s Zepbound (tirzepatide) crushed Novo Nordisk’s Wegovy (semaglutide), delivering a 47% greater relative weight loss over 72 weeks. The results of the SURMOUNT-5 trial, released in late 2024, could reshape the landscape of obesity treatment—and with it, the investment strategies of healthcare investors.

The Trial: A Landmark for Zepbound

The SURMOUNT-5 study enrolled 751 adults with obesity or overweight (but no diabetes), randomly assigning them to Zepbound or Wegovy. The results were unequivocal:
- Zepbound users lost an average of 20.2% of their body weight (50.3 pounds), compared to 13.7% (33.1 pounds) for Wegovy.
- A stunning 31.6% of Zepbound patients achieved ≥25% weight loss, versus just 16.1% on Wegovy.
- The statistical significance was overwhelming: p < 0.001 for all key endpoints, meaning the results were highly unlikely to be due to chance.

The trial’s design highlights Zepbound’s edge. Unlike Wegovy, which mimics GLP-1, Zepbound combines GLP-1 and GIP (glucose-dependent insulinotropic polypeptide) receptor agonism. This dual mechanism likely amplifies metabolic effects, driving superior satiety and fat metabolism.

Market Context: A Battle for Billions

The weight loss drug market is already massive, with $6 billion in annual sales projected by 2030. Wegovy, launched in 2021, has been a juggernaut, but Zepbound’s trial results suggest it could soon overtake its rival.

Lilly’s stock has lagged Novo’s in recent years, but the SURMOUNT-5 data could change that. Analysts estimate Zepbound’s peak sales could hit $5 billion annually, rivaling Wegovy’s current $4.5 billion run rate. Meanwhile, supply chain issues plague both drugs: while Lilly’s tirzepatide was delisted from the FDA shortage list in 2024, Novo’s semaglutide remains in short supply.

Competitive Risks and Regulatory Wins

Zepbound’s victory isn’t just about efficacy. In December 2024, the FDA approved it for moderate-to-severe obstructive sleep apnea, the first drug-based treatment for the condition. Wegovy, by contrast, won a cardiovascular risk reduction indication in 2024—but Zepbound’s broader indications and mechanism could give it an edge.

Novo’s experimental combo drug, CagriSema (a GLP-1/GIP mix), stumbled in trials, failing to match Zepbound’s results. Its underperformance—only 14% weight loss in diabetics—led to a 10% drop in Novo’s stock when results were reported. Zepbound’s head start in the dual-agonist race now looks decisive.

The Bottom Line: Why This Matters for Investors

The data is clear: Zepbound outperforms Wegovy in both weight loss and key comorbidities. For investors, this means:
1. Lilly’s pipeline gains credibility, with Zepbound positioned to dominate a $6B market.
2. Supply chain improvements for tirzepatide (Zepbound’s active ingredient) could unlock growth, especially as generics for older GLP-1 drugs (like liraglutide) undercut competition.
3. Novo’s stock faces headwinds as Zepbound encroaches on its core market.

Risks to Consider

Regulatory hurdles: While Zepbound’s FDA approvals are solid, long-term cardiovascular safety data is still pending.
Cost and access: Insurance coverage and pricing negotiations could limit uptake, though Zepbound’s efficacy may push payers to cover it.
Generic competition: While Zepbound’s patents run until the 2030s, Novo’s cheaper generics for older drugs could pressure margins.

Conclusion: Zepbound’s Moment

The SURMOUNT-5 trial isn’t just a win for Lilly—it’s a seismic shift in the weight loss market. With superior efficacy, expanding indications, and a manufacturing edge, Zepbound is poised to become the gold standard. For investors, this means:

Lilly (LLY) is a buy on Zepbound’s potential to capture 50%+ of new weight loss prescriptions.
Novo (NVO) faces a reckoning, as its reliance on Wegovy’s current dominance may wane.

The numbers speak for themselves: Zepbound’s 20.2% average weight loss and 31.6% of patients hitting ≥25% loss are game-changers. With a dual-mechanism that’s clinically proven and a growing pipeline of indications, this drug could redefine obesity treatment—and Lilly’s stock could finally get the valuation it deserves.

In the battle for weight loss supremacy, Zepbound is no longer just a contender—it’s the champion.

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