Despite CagriSema's Phase 3 Setback, Novo Nordisk Counters with Oral Wegovy
CagriSema's Second Head-to-Head Defeat
Novo Nordisk's (NVO) weekly composite CagriSema is a Phase 3 candidate combining cagrilintide, an amylin receptor agonist, and semaglutide, a GLP-1 receptor agonist. In the Phase 3 REIMAGINE-4 trial for patients with type 2 diabetes, the 68-week weight loss rate was 15.2%, meeting the non-inferiority criteria compared to Eli Lilly's (LLY) tirzepatide at 15.8%. However, the reduction in HbA1c was 1.9 percentage points, falling short of the 2.2 percentage points achieved by tirzepatide, thus failing to meet the non-inferiority endpoint. Previously, in the Phase 3 REDEFINE-4 trial for obese patients, the 84-week weight loss was 20.2% for CagriSema and 23.6% for tirzepatide, also missing the non-inferiority target. These results highlight that surpassing market-leading drugs is crucial for the value assessment of next-generation products, rather than absolute efficacy.
Lilly Sets the Commercial Benchmark
Tirzepatide is a dual GIP/GLP-1 receptor agonist, marketed as Mounjaro for type 2 diabetes and Zepbound for chronic weight management. The U.S. FDA approved Mounjaro on May 13, 2022, and Zepbound on November 8, 2023, with combined sales of USD 36.5 billion in 2025. Existing standard treatments include semaglutide-based Ozempic and Wegovy, along with tirzepatide, while late-stage competitors include Lilly's Phase 3 retatrutide, Amgen's (AMGN) MariTide, and Boehringer Ingelheim's survodutide. Therefore, CagriSema must demonstrate differentiation not only in terms of approval but also in ease of administration, tolerability, price, and manufacturing capacity.
Oral Wegovy Creates a Defensive Line
Wegovy is the obesity brand of the GLP-1 receptor agonist semaglutide. The injectable formulation was approved in the U.S. on June 4, 2021, and the 25 mg oral formulation received FDA approval in December 2025, with a launch in January 2026. Since its launch, the oral Wegovy has surpassed 5 million cumulative prescriptions, accounting for approximately 90% of oral obesity drug prescriptions in the U.S., outpacing Lilly's oral GLP-1 agonist Foundayo (orforglipron). However, due to price/rebate pressures and increased competition in the injectable market, U.S. sales of injectable Wegovy decreased by 22% year-on-year. The rapid adoption of the oral formulation serves as a short-term growth driver, absorbing the development volatility of CagriSema by attracting patients who prefer non-injectable options.
Recovery in Performance and Remaining Execution Risks
Novo Nordisk recorded adjusted revenue of DKK 78.5 billion and adjusted operating profit of DKK 33.389 billion in the first half of 2026, and raised its full-year outlook based on the early performance of oral Wegovy. However, CagriSema is in the process of being submitted to the FDA for obesity indication in December 2025, with a decision expected in the fourth quarter of 2026. The head-to-head clinical results may pose challenges to post-launch prescription access and price negotiations. IQVIA estimates the global obesity drug market at USD 66 billion in 2025 and USD 92 billion in 2026, while J.P. Morgan forecasts the incretin market to reach USD 200 billion in 2030. In this market, maintaining the lead in oral formulations and demonstrating clinical differentiation of next-generation candidates are key factors in determining corporate value, as much as increasing production capacity.
Novo Nordisk has demonstrated short-term performance resilience with adjusted operating profit of DKK 33.389 billion in the first half of 2026 and 5 million cumulative prescriptions for oral Wegovy. However, the fact that CagriSema's HbA1c reduction in the Phase 3 REIMAGINE-4 trial was 1.9 percentage points, compared to 2.2 percentage points for tirzepatide, weakens the competitive advantage of subsequent products. From an R&D perspective, while the amylin/GLP-1 combination achieved 15.2% weight loss, it is clear that the challenge remains to enhance blood sugar efficacy compared to dual GIP/GLP-1 agonists. In the industry, in addition to FDA-approved Mounjaro and Zepbound, Phase 3 retatrutide, MariTide, and survodutide are entering the market, expanding the differentiation criteria from efficacy to tolerability, ease of administration, and price. Considering the USD 92 billion obesity drug market in 2026 and the USD 200 billion incretin market in 2030, maintaining the approximately 90% prescription share of oral Wegovy and the FDA decision on CagriSema in the fourth quarter of 2026 will be key variables in determining medium- to long-term market share and valuation.