How Novo Nordisk is building a post-semaglutide strategy: Inside its metabolic pipeline and innovation bets

Novo Nordisk A/S (CPH: NOVO‑B) is entering a pivotal new phase in its obesity drug strategy, moving decisively beyond its blockbuster semaglutide franchise with a diversified late-stage pipeline. The Danish pharmaceutical firm is advancing multiple next-generation therapies—including the dual GLP-1 and amylin receptor agonist amycretin, the fixed-dose combination CagriSema, and a high-dose oral semaglutide formulation—as it prepares for intensifying global competition in the obesity treatment market.

In June 2025, Novo Nordisk confirmed its plans to initiate phase 3 trials for both injectable and oral versions of amycretin, following the publication of promising phase 1 and 2 results showing weight reductions of up to 24.3% in certain patient groups. Meanwhile, the company’s CagriSema candidate recently completed multiple phase 3 trials with mixed but clinically significant results, and regulatory review is underway for oral semaglutide in the obesity indication.

How is amycretin positioned to lead Novo Nordisk’s post-semaglutide obesity strategy in 2026 and beyond?

Amycretin is a first-in-class unimolecular therapy that combines GLP-1 and amylin receptor agonism into a single peptide, with once-weekly subcutaneous and once-daily oral formulations in development. Novo Nordisk’s internal data, presented at the American Diabetes Association 2025 meeting and published in The Lancet, showed weight reductions of 24.3% in patients on 60 mg subcutaneous doses over 36 weeks, and 13.1% weight loss with oral doses over 12 weeks, both significantly outperforming placebo.

What makes amycretin stand out is its potential to deliver dual-pathway weight control—enhancing satiety, slowing gastric emptying, and regulating glucose through GLP-1 and amylin synergy. The therapy’s tolerability profile was consistent with early-stage GLP-1 agents, with most adverse events being mild to moderate gastrointestinal symptoms that resolved over time. Institutional investors responded positively to the announcement that global phase 3 studies would begin in early 2026, with analysts widely regarding amycretin as a leading candidate to replace semaglutide as Novo Nordisk’s flagship weight management therapy by 2028.

How have the phase 3 results of CagriSema influenced market sentiment and Novo Nordisk’s broader metabolic pipeline?

CagriSema, a fixed-dose combination of semaglutide and the long-acting amylin analog cagrilintide, was initially positioned as a semaglutide-enhancing therapy capable of matching or surpassing Eli Lilly’s dual-agonist tirzepatide. In December 2024, the REDEFINE 1 phase 3 trial demonstrated a 22.7% weight loss over 68 weeks, slightly above expectations. However, the follow-up REDEFINE 2 trial in people with type 2 diabetes delivered more modest results, with a 15.7% weight loss.

Market reaction to the REDEFINE data was mixed. While the results reinforced the drug’s potential, investor sentiment cooled after the initial hype around transformational efficacy. Analysts noted that CagriSema’s performance, while impressive, may face challenges in payer negotiations due to its pricing assumptions, formulation complexity, and comparison with single-molecule dual agonists. Still, Novo Nordisk confirmed that regulatory filings are on track for early 2026, and the candidate remains a critical component of its near-term obesity pipeline.

What recent challenges have emerged around semaglutide and how is Novo Nordisk adapting its commercial strategy?

Despite strong sales momentum, Novo Nordisk’s semaglutide franchise has come under increasing pressure. In the first quarter of 2025, Wegovy and Ozempic generated a combined US$7.2 billion in global revenue, maintaining a slight lead over Eli Lilly’s Mounjaro and Zepbound. However, analysts observed that Lilly’s tirzepatide-based therapies are outperforming semaglutide in clinical head-to-heads and gaining traction in new markets, including Asia-Pacific and parts of Europe.

To preserve market share, Novo Nordisk has turned to format flexibility as a strategic lever. Its oral semaglutide 50 mg candidate, which achieved 16.6% weight loss over 64 weeks in the OASIS 1 study, is now under regulatory review in the United States and European Union. This move signals an effort to appeal to patients averse to injectables while reinforcing GLP-1 dominance in high-volume segments.

Additionally, leadership transition at Novo Nordisk has introduced further uncertainty. CEO Lars Fruergaard Jørgensen’s announced departure has raised questions about execution stability, although succession planning is reportedly well advanced. Some institutional investors have cited the leadership shift and recent clinical readouts as contributing factors behind a volatile stock performance in Q2 2025.

How is Novo Nordisk expanding through external partnerships and small-molecule innovation?

Novo Nordisk is also broadening its metabolic disease platform through external collaborations, particularly in the small-molecule space. It has entered a strategic partnership with Septerna to explore oral GPCR-targeted agonists, and recently licensed triple-G peptides from United BioPharma, aimed at expanding its reach into polyhormonal metabolic therapeutics.

These deals are intended to supplement the peptide-based pipeline with easier-to-manufacture oral candidates, reducing supply-chain bottlenecks and enhancing access in markets with cold-chain constraints. Analysts see these partnerships as long-term plays that could offer cost-effective alternatives to semaglutide and amycretin, particularly in middle-income countries.

What is the current institutional sentiment around Novo Nordisk’s pipeline after recent data releases?

Following the publication of amycretin’s early trial data and confirmation of phase 3 progression, institutional sentiment appears to be stabilizing. In early June 2025, shares of Novo Nordisk rebounded nearly 6% after a two-month correction linked to disappointing CagriSema data and competitive pressure from Eli Lilly.

Portfolio managers have highlighted the diversified nature of Novo Nordisk’s metabolic pipeline as a strategic buffer against individual trial outcomes. Amycretin is especially viewed as a credible contender to reshape the dual-agonist obesity space, while oral semaglutide is anticipated to broaden reach among new-to-treatment patients. CagriSema, although no longer considered a breakthrough, is still expected to secure niche positioning, particularly for combination therapy scenarios in high-risk patients.

What does the future hold for Novo Nordisk’s obesity portfolio in light of market competition and clinical timelines?

Novo Nordisk is preparing for an intense period of clinical execution between 2025 and 2027. Key milestones include phase 3 trial launches for amycretin in early 2026, potential approvals for CagriSema and oral semaglutide in late 2026 or early 2027, and strategic investments in both internal pipeline progression and external technology acquisition.

Analysts forecast that Novo Nordisk could maintain its leadership in global obesity drug revenues through 2027, but only if amycretin delivers on phase 3 expectations. The dual formulation strategy—injectable for high-efficacy cases, oral for broader adoption—will be critical in preserving pricing power and market access. Furthermore, real-world outcomes and cardiovascular risk reductions may become gating factors for payer support across key geographies.

In the long term, Novo Nordisk’s ability to evolve from a semaglutide-centric company to a diversified obesity platform operator will depend on the seamless integration of these pipeline assets and its agility in responding to market dynamics. As more players enter the field, from Eli Lilly to Pfizer and Amgen, the Danish drugmaker’s innovation engine and supply chain resilience will be continually tested.