Novo Nordisk Decides to Rewrite Its Fate with AI

This 'multi-pronged bet' strategy can be understood as a cautious approach—akin to 'not putting all your eggs in one basket.' Yet equally impossible to ignore is Novo Nordisk’s anxiety over the pace of change. TONACEA 02 The Triple Crisis Novo Nordisk had a particularly disappointing year in 2025. In that year, tirzepatide generated $36.507 billion in revenue, surpassing semaglutide’s $36.1 billion—and officially claimed the title of 'world’s top-selling drug.' Compounding the setback, the gap widened further in 2026. Public data shows that in Q2 2026, Lilly captured 60.9% of the global obesity drug market share, while Novo Nordisk held only 38.8%. According to its semi-annual report, Lilly’s total revenue for H1 2026 reached $42.773 billion, up 51% year-on-year; its entire tirzepatide portfolio generated $27.693 billion in sales, up 88% year-on-year. By contrast, Novo Nordisk’s full semaglutide portfolio brought in approximately $17.3 billion in H1 2026—roughly $10 billion behind tirzepatide. Recall that in the same period of 2025, semaglutide had still led tirzepatide by nearly $2 billion. In just one year, the balance of power had completely reversed. This overwhelming competitive pressure triggered the second crisis: ruthless punishment from capital markets. Also in 2025, Novo Nordisk underwent a major management shake-up and suffered a sharp stock price decline. In February 2026, the company disclosed that its full-year 2026 sales and operating profit could fall between 5% and 13%. This forecast far exceeded analysts’ prior expectation of a 1.4% decline—and marked the company’s first annual sales drop in nine years. Its stock plunged over 14% the next day. By June this year, the former 'king of European equities' had a market capitalization of only about $191.2 billion—down more than $450 billion from its peak over a year earlier. The internal structural contradictions are equally undeniable: Novo Nordisk itself was born from a 'century-long marriage' fraught with flaws. In 1989, Novo and Nordisk—longtime rivals in the insulin space—reluctantly merged to counter Eli Lilly. But the merger amounted to a strategic ceasefire, not true integration. Nordisk excelled in technology and academia; Novo dominated marketing and distribution channels. This inherent tension slowed decision-making. Novo Nordisk once reacted sluggishly to the genetic engineering revolution, even nearly disbanding its GLP-1 research team—a project then considered marginal. Even after liraglutide and semaglutide launched, senior leadership remained entrenched in the 'insulin success trap,' viewing GLP-1 as merely a secondary product. Arrogant inertia left the giant ill-equipped to respond as the weight-loss drug market shifted—from efficacy competition to a C-end battle over distribution, pricing, and consumer mindshare. While Lilly aggressively built out its U.S. market presence and engaged consumers directly via e-commerce, Novo Nordisk clung stubbornly to traditional B-end physician promotion—going so far as to discourage doctors from prescribing due to insufficient production capacity, effectively ceding market share. Amid this perfect storm, Doustdar stepped forward. Since assuming the CEO role last August, he launched a large-scale cost-cutting initiative targeting annual savings of DKK 8 billion by end-2026. On the product front, Doustdar spearheaded the launch of an oral version of Wegovy—temporarily placing Novo Nordisk ahead of Lilly in the oral weight-loss drug market. As of mid-July, Wegovy tablets accounted for 86.5% of prescriptions in the U.S. oral GLP-1 weight-loss market.

Novo Nordisk Terminates Phase III Clinical Trial

HERMES’s primary endpoint is the time to first occurrence of the composite of cardiovascular death, hospitalization for heart failure, or urgent heart failure visit; ATHENA aims to assess ziltivekimab’s impact on patients’ health status. Prior to this, on July 31, 2026, Novo Nordisk announced that its pivotal Phase III ZEUS cardiovascular outcomes trial failed to meet its primary endpoint. The study evaluated ziltivekimab’s efficacy in reducing the risk of major adverse cardiovascular events (MACE)—defined as cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke—in patients with atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD), and inflammation. Key results showed that although ziltivekimab demonstrated target engagement and inhibition of the interleukin-6 (IL-6) pathway—as evidenced by expected reductions in free IL-6 and high-sensitivity C-reactive protein (hsCRP) levels—this did not translate into a reduction in MACE risk, with a hazard ratio of 0.99. The ZEUS trial enrolled over 6,300 patients with ASCVD and CKD who also exhibited cardiovascular inflammation (hsCRP ≥ 2 mg/L). Patients received either monthly ziltivekimab or placebo on top of standard care. Regarding safety, the overall incidence of serious adverse events was similar between groups; however, the rate of serious infections was higher among patients receiving ziltivekimab than among those receiving placebo—a finding consistent with the mechanism of IL-6 pathway inhibition. No difference in all-cause mortality was observed between the two groups. This series of setbacks delivers a major blow to Novo Nordisk’s strategy to expand beyond obesity and diabetes. Earlier this July, news of the ZEUS trial’s failure triggered a stock price drop exceeding 10%. Given ziltivekimab’s relatively minor contribution to Novo Nordisk’s overall pipeline, the market’s reaction may seem somewhat excessive—but strategically, the outcome is negative: it eliminates one of Novo Nordisk’s most reliable growth opportunities outside obesity, reinforcing the company’s heavy dependence on commercial execution in obesity—and on external innovation—to drive future growth.

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Novo Nordisk faces investor pressure to diversify beyond its blockbuster weight-loss drugs amid rising competition from Eli Lilly and impending semaglutide patent expiries. Analysts suggest acquisitions or pivoting to other therapeutic areas to secure long-term growth.

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