Novo Nordisk’s ambitious plans to solidify its dominance in the obesity treatment market hit a speed bump this week with the unveiling of data from two major trials. On one hand, the STEP-UP Phase 3b study showcased that a higher dose of semaglutide (7.2 mg) achieved 20.7% mean weight loss over 72 weeks, surpassing the 17.5% seen with the standard 2.4 mg dose. On the other, results from the REDEFINE 1 Phase 3 trial for CagriSema—a fixed-dose combination of cagrilintide and semaglutide—delivered a mixed message: impressive but short of Novo’s sky-high promise of 25% weight loss, clocking in at 22.7%.
For investors and industry watchers, these developments reflect the tightrope Novo must walk as the GLP-1 race accelerates, with competitors like Eli Lilly pressing their advantage and new players eyeing a slice of the multibillion-dollar obesity market.
Semaglutide 7.2 mg: Solid Performance, Familiar GI Baggage
The STEP-UP data reinforced semaglutide’s place as a cornerstone of Novo’s obesity strategy. At the higher 7.2 mg dose, the therapy delivered statistically significant weight loss versus placebo, meeting its primary endpoint. However, the gains came with familiar gastrointestinal side effects—a hallmark of GLP-1 drugs—that, while tapering over time, may raise concerns about patient adherence as doses escalate.
Still, the trial design avoided “forced dose escalation,” allowing patients to ramp up at their own pace—a key differentiator that could mitigate dropout rates seen in other GLP-1 trials. This approach could set a precedent for future studies, especially as Novo faces increasing scrutiny over patient-centricity in trial protocols.
CagriSema: Impressive, Yet Short of Lofty Goals
CagriSema’s Phase 3 data offered a clear but nuanced takeaway: the drug works—just not as well as Novo had hoped. While 22.7% weight loss is nothing to scoff at, missing the company’s self-imposed 25% target rattled investors, slashing Novo’s market cap by $100 billion as shares plummeted over 20%. The results were further complicated by the trial’s flexible dosing protocol, with only 57% of participants reaching the highest dose at 68 weeks.
On paper, CagriSema outperformed high-dose semaglutide, placebo, and even Eli Lilly’s Zepbound in certain scenarios. But with Lilly’s next-generation therapies—such as retatrutide—already achieving >24% weight loss at just 48 weeks, Novo’s window to claim “best-in-class” status is narrowing.
Competitive Pressures Mount as Novo Faces Reality Check
Novo’s challenges don’t end with the market’s reaction to CagriSema. Eli Lilly’s Zepbound recently bested semaglutide in a head-to-head trial, achieving 20.2% weight loss versus Wegovy’s 13.7%. Meanwhile, Lilly’s pipeline continues to outpace Novo’s, with retatrutide and the oral GLP-1 orforglipron advancing swiftly.
Further complicating matters, Novo’s acquisition of Catalent, intended to address semaglutide supply chain bottlenecks, will require years to pay off—a timeline that competitors like Lilly and Amgen, with their own GLP-1 candidates, are unlikely to wait out.
Where Does Novo Go From Here?
CagriSema remains a critical piece of Novo’s strategy, especially as the company eyes the lucrative combination therapy market. With further data from REDEFINE 2 targeting type 2 diabetes expected in 2025, the story of CagriSema is far from finished. However, Novo must recalibrate expectations—not just for Wall Street but for patients increasingly drawn to Lilly’s perceived edge in innovation and outcomes.
Ultimately, Novo remains a powerhouse in the GLP-1 space, second only to Lilly. But with 16 GLP-1 contenders potentially entering the market by 2030, the pressure is on for Novo to demonstrate not just incremental improvements but true breakthroughs. For now, the high-dose semaglutide results and CagriSema’s promise underscore Novo’s resilience, even as the GLP-1 race grows fiercer by the day.
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