Earnings Call Transcript
NOVO NORDISK A S (NVO)
Earnings Call Transcript - NVO Q4 2025
Operator, Operator
Good day, and thank you for standing by. Welcome to the Q4 2025 Novo Nordisk Earnings Conference Call. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Michael Novod, Head of Investor Relations. Please go ahead.
Michael Novod, Head of Investor Relations
Thank you very much, and welcome to this Novo Nordisk Earnings Call for the Full Year of 2025. My name is Michael Novod. I'm the Head of Investor Relations at Novo Nordisk. With me today, I have CEO of Novo Nordisk, Mike Doustdar; EVP, Product and Portfolio Strategy, Ludovic Helfgott; EVP, U.S. Operations, Dave Moore; EVP, Research and Development and Chief Scientific Officer, Martin Holst Lange; and Chief Financial Officer, Karsten Munk Knudsen. All speakers will be available for the Q&A session. Today's call is being webcasted live, and a recording will be made available on our website. The call is scheduled to last 1 hour. Next slide, please. The presentation is structured as outlined on Slide 2. Please note that all sales and operating profit growth statements will be at constant exchange rates unless otherwise specified. Next slide, please. We need to advise you that this call will contain forward-looking statements. These are subject to risks and uncertainties that could cause actual results to differ materially from expectations. For further information on the risk factors, please see the company announcement for the full year 2025 and the slides prepared for this presentation. With that, over to you, Mike, for an update on our strategic aspirations.
Maziar Doustdar, CEO
Thank you, Michael. Next slide, please. In 2025, Novo Nordisk delivered 10% sales growth and operating profit growth of 6%. We sharpened our strategic focus in 2025, doubling down in our core therapeutic areas of obesity and diabetes. This year marks the conclusion of the 2025 strategic aspirations that were established back in 2019. Since then, we have more than doubled our sales and operating profit, and our obesity care sales have increased from DKK 6 billion in 2019 to DKK 82 billion in 2025. Rare disease is now positioned for sustained growth with the late-stage pipeline assets, Mim8, now called denecimig and etavopivat. Furthermore, over DKK 300 billion has been returned to our shareholders since 2019. Most importantly, we have increased our reach by an additional 16 million people with our obesity and diabetes treatments. This quarter, we saw several exciting readouts, including the next-generation treatment for type 2 diabetes with the Phase II readout of zenagamtide and Phase III readout for CagriSema. Novo Nordisk also continued to build upon its pipeline across therapy areas. Martin will discuss this in more detail later in the call. By late 2025, we received FDA approval for the Wegovy pill, the first oral GLP-1 for obesity and submitted CagriSema in the U.S. Dave will speak more to the Wegovy pill later, but we are encouraged by the early uptake of the pill and what we see these milestones mean for people living with obesity. We are treating nearly 46 million people with our innovative medicines, reflecting Novo Nordisk's commitment to innovation and the ongoing efforts to expand access to our therapies worldwide. Finally, Karsten will come back to it, but we have released our 2026 guidance, which reflects a year of pricing headwinds. We do not take this lightly, and we will do all we can to pursue the volume opportunities in obesity and diabetes. Next slide, please. Yesterday, we also announced changes to the executive management team. Dave Moore has decided to leave Novo Nordisk for personal reasons after more than 8 years with the company. Dave began his Novo journey in 2017 and returned to Novo in 2022 after a time outside of the company to lead our global business development area before returning to the U.S. as the Executive Vice President of U.S. Operations in January of 2025. Dave has moved the needle throughout his time at Novo from driving the blockbuster launch of Ozempic to leading the acquisition of 3 Catalent manufacturing sites to overseeing the launch of the Wegovy pill in the U.S. In addition, Ludovic Helfgott has decided to leave Novo Nordisk to pursue new opportunities. Ludo joined Novo Nordisk back in 2019 to lead what was back then called Biopharm business and eventually became our rare disease therapy area. Ludovic's patient-first leadership is reflected in Novo Nordisk's strong presence in rare blood and endocrine disorders today. Ludovic was able to translate this passion across all of our therapy areas over the last 10 months as the Head of Product and Portfolio Strategy. On behalf of Novo Nordisk and myself, I would like to thank Dave and Ludovic for their bold and steady leadership. After a thoughtful selection process over the last few months, I'm very pleased to announce the addition of Jamey Millar and Hong Chow to Novo Nordisk and the executive management team. Next slide, please. Starting February 5, Jamey Millar joins Novo Nordisk as an Executive Vice President of U.S. Operations. Jamey brings more than 30 years of extensive leadership experience in the pharmaceutical industry with a proven track record in launching major therapies and shaping commercial strategy. He joins us from UnitedHealth Group, where he served as the CEO of Optum Specialty Holdings and brings deep expertise in U.S. market access and product lifecycle management. Beginning February 15, Hong Chow will join Novo Nordisk as an Executive Vice President of Product and Portfolio Strategy. Hong brings deep global leadership experience to Novo Nordisk serving as the Executive Vice President and Head of China and International at Merck Healthcare and leading their global cardiovascular metabolism and endocrine portfolio. Her leadership in advancing innovation, health equity, and large-scale product strategies at companies such as Merck, Roche, and Bayer demonstrates her outstanding capability to drive our vision forward. We look forward to welcoming Jamey and Hong to Novo Nordisk this month, and both Dave and Ludo will help to ensure a successful transition to their successors throughout the end of this quarter. I will now hand over to Ludo for an update on our commercial execution in 2025.
Ludovic Helfgott, EVP, Product and Portfolio Strategy
Thank you, Mike, and please turn to the next slide. The global GLP-1 market grew over 30% in 2025. Novo Nordisk total sales increased by 10% as U.S. operations grew 8% and International Operations grew 14%. Sales growth was positively impacted by one-offs in the U.S. Our GLP-1 sales in diabetes increased by 6%, driven by U.S. operations, plus 5% and International Operations growing 7%. Insulin sales decreased by 1%. U.S. operations increased by 2%, positively impacted by positive channel and payer mix and partially countered by a decline in volume. International Operations decreased by 2%, impacted by market share losses. Obesity care sales increased 31% in 2025, driven by both operating units. U.S. operations grew 15% and IO grew 73%. In both geographies, growth was driven by Wegovy. Our Rare Disease sales increased by 9%. This was driven by sales increase in the U.S. operations of 7% and in International Operations of 10%. In both operating units, the sales increase was primarily driven by the rare endocrine disorder products, mainly due to Sogroya launch uptake. Next slide, please. Sales in International Operations were driven by GLP-1 products in obesity and diabetes care. The GLP-1 volume growth in International Operations was 44% in 2025. And Novo Nordisk remains the overall GLP-1 market leader with a 62% volume market share. GLP-1 diabetes sales increased by 7%, driven by the sales growth of Ozempic. In Region China, GLP-1 diabetes sales decreased by 5%, which was negatively impacted by wholesaler inventory movements. Total obesity care sales grew up to DKK 31 billion in 2025. Wegovy was launched in 35 new countries in 2025, more than tripling the number of launches back in 2024. Sales of Wegovy reached DKK 28 billion in '25, growing 134%. We continue to see GLP-1 market growth in International Operations. A large unmet need remains, and penetration rates are low. Looking into '26, we plan to further expand the obesity and diabetes markets in IO through new online channels and partnerships and by bringing new products to patients with the ongoing rollout of semaglutide 7.2 milligrams for weight loss and Ozempic 2-milligrams for diabetes in certain markets. And with that, I would like to thank my colleagues and the entire Novo Nordisk organization for a tremendous 7 years. It's been a privilege to work on impactful medicines that have already and hopefully soon will make it to the hands of patients. And now I will hand it over to Dave for an update on U.S. operations.
David Moore, EVP, U.S. Operations
Thank you, Ludo. Next slide, please. Sales of GLP-1 diabetes care products in the U.S. increased by 5% in 2025. The sales increase was driven by continued uptake of Ozempic, partially countered by Victoza and Rybelsus. Ozempic sales in the U.S. were positively impacted by gross to net sales adjustments and GLP-1 diabetes market growth, partially countered by market share losses and lower realized prices. Weekly Ozempic prescriptions are currently around 610,000. The GLP-1 diabetes market grew just over 10% in the fourth quarter of 2025 compared to the fourth quarter of 2024. In the U.S., we continue to meet people with type 2 diabetes where they are, including through our self-pay offering for Ozempic that is currently around 8,000 prescriptions per week. We also received FDA approval for the updated formulation of the Ozempic pill, formerly known as Rybelsus, and that happened last week. Next slide, please. As Mike noted earlier, 2025 ended with an exciting milestone for Novo Nordisk and importantly, people living with obesity in the U.S. The Wegovy pill was approved by FDA on December 22. And thanks to outstanding efforts across our entire organization, we were able to bring the first and best-in-class oral GLP-1 for weight management to the U.S. market on January 5. The Wegovy pill is the only GLP-1 peptide formulated into a pill, delivering the weight loss efficacy of injectable Wegovy in a once-daily oral tablet. When looking separately at the Phase III trial data in obesity for the Wegovy pill and for orforglipron, the Wegovy pill shows around 35% greater reported weight loss. We have seen encouraging early uptake of the Wegovy pill. Our compiled data shows that total prescriptions are around 50,000 for the week ending January 23, with around 45,000 of these prescriptions coming through self-pay. The uptake is over twice that of any prior anti-obesity drug launches in the United States. Though it is still early in the launch, most prescriptions appear to be for patients new to these medications, suggesting the market is expanding. The Wegovy Pill is offered at over 70,000 retail pharmacies and through NovoCare Pharmacy and numerous telehealth partners. Commercial access for the Wegovy pill is progressing with coverage currently via CVS, Prime, Optum, and Anthem, amounting to just below half the covered lives we have for injectable Wegovy. We continue working to develop reimbursed access and broaden reach through more partnerships in order to provide people with obesity an oral therapeutic option with a competitive label of Wegovy and best-in-class weight loss. Next slide, please. Wegovy sales increased by 16% in U.S. operations in 2025. The Wegovy sales growth was driven by increased volumes, partially countered by lower realized prices. In the holiday week ending January 23, Wegovy had around 230,000 weekly prescriptions. The recent decline in injectable Wegovy prescriptions at the start of 2026 is largely attributed to benefit changes at the turn of the year, including several states that are dropping Medicaid coverage of anti-obesity medicines. The combined injectable and pill Wegovy brand is currently now more than 75,000 weekly NBRxs, and that makes it the leading anti-obesity medication franchise measured by NBRx in the U.S. In the last year, the branded anti-obesity market has more than doubled in size. U.S. operations have prioritized making our anti-obesity medications available to more people through multiple avenues to meet the outstanding unmet need. Novo Nordisk launched NovoCare Pharmacy in March 2025. And together with retail and telehealth, total self-pay now makes up around 30% of total injectable Wegovy prescriptions. In under 1 year, our increased efforts in the self-pay channel have resulted in close to 120,000 current weekly TRxs across Wegovy and Ozempic brands, and we continue to add more patients daily. Novo Nordisk will continue to invest in the expansion of the direct-to-patient initiatives like the recently announced collaboration with Amazon Pharmacy. In November, we announced that Novo Nordisk entered an agreement with the U.S. administration, including coverage for obesity medicines in U.S. Medicare Part D via the CMMI pilot program. We are encouraged that more patients will have affordable access to our medicines, and we anticipate that coverage will begin around the middle of the year. In addition to access, we remain focused on bringing innovation to the market. Novo Nordisk submitted the high-dose semaglutide 7.2 milligrams to FDA in November. It's under the CNPV pilot program, and we anticipate a decision during the first quarter of 2026. Furthermore, CagriSema has been submitted to the FDA in December, and we expect a decision towards the turn of the year. As my time at Novo Nordisk comes to an end, I'm excited about its future and proud of the positive impact I've witnessed on patients worldwide, and I look forward to seeing Novo Nordisk continue with this mission. And now I'll turn it over to Martin for an update on R&D.
Martin Lange, EVP, Research and Development
Thank you, Dave. Please turn to the next slide. This week, we announced the top line results from REIMAGINE 2, a Phase III trial for CagriSema in type 2 diabetes. The trial involved around 2,700 participants with type 2 diabetes who were not adequately controlled with metformin, with or without an SGLT2 inhibitor. Participants were randomly assigned to receive either CagriSema 2.4 milligram or 1 milligram, semaglutide 2.4 milligram or 1 milligram, cagrilintide 2.4 milligram, or a placebo. The primary endpoint was the superiority of CagriSema over Semaglutide in terms of A1c reduction, with body weight change as a secondary endpoint. Approximately 40% of participants were using an SGLT2 inhibitor before the trial began. Please go to the next slide. In REIMAGINE 2, CagriSema 2.4 milligram demonstrated a greater A1c reduction and weight loss compared to semaglutide 2.4 milligram. Assuming all participants adhered to treatment and had a mean A1c baseline of 8.2%, CagriSema 2.4 milligram achieved a reduction of 1.91 percentage points, compared to 1.76 percentage points with semaglutide 2.4 milligram. Additionally, CagriSema 2.4 milligram led to a weight loss of 14.2%. More than 40% of those treated with CagriSema 2.4 milligram lost over 15% of their weight, and about one in four lost over 20%. The trial indicated that CagriSema had a safe and well-tolerated profile. The most common adverse events were gastrointestinal, mostly mild to moderate, and decreased over time. This data aligns with the recent top line results from REIMAGINE 3, where CagriSema as an add-on to basal insulin resulted in an A1c reduction of 2.33 percentage points and a weight loss of 12% at 40 weeks, all superior to placebo. We are expecting results from the pivotal REIMAGINE 1 trial in the first quarter of 2026. We are also anticipating data from the long-term safety and efficacy trial, REDEFINE 3. Following these results, Novo Nordisk will work with authorities on the regulatory pathway for CagriSema in type 2 diabetes. In summary, CagriSema has shown superior results in both glycemic control and weight reduction, representing a highly effective treatment option for those managing type 2 diabetes alongside weight concerns. Next slide, please. In November, we reported positive headline results from the initial evaluation of zenagamtide, previously known as amycretin, in people with type 2 diabetes. This trial focused on the efficacy, safety, and pharmacokinetics of once-weekly subcutaneous and once-daily oral zenagamtide compared to placebo. It included around 450 participants with type 2 diabetes inadequately controlled on metformin, with or without an SGLT2 inhibitor, which is standard care. About 40% of participants used an SGLT2 inhibitor at baseline. The trial tested six subcutaneous doses ranging from 0.4 milligrams to 40 milligrams and three oral doses ranging from 6 milligrams to 50 milligrams. From a baseline mean HbA1c of 7.8%, once-weekly zenagamtide lowered A1c by up to 1.8 percentage points at week 36 in a dose-dependent manner, assuming all participants adhered to treatment. Up to 89.1% of participants achieved an A1c level below 7%. Additionally, oral zenagamtide led to dose-dependent reductions of A1c up to 1.5 percentage points by week 36 from a baseline of 8%, with nearly 78% of participants reaching an A1c below 7%. These improvements were statistically significant compared to placebo, confirming the trial's primary endpoint. Both formulations of zenagamtide appear to be safe and well-tolerated, consistent with other incretin and amylin-based therapies. This data further supports the potential of zenagamtide as a next-generation diabetes treatment, and we look forward to initiating an extensive Phase III program called AMBITION for type 2 diabetes and other indications in the latter half of 2026. Moreover, the Phase III obesity program, called AMAZE, will start in the first quarter of 2026. As a reminder, the Phase Ib/IIa clinical trial involving incretin in individuals with obesity or overweight demonstrated a 22% weight loss using a 20-milligram dose after 36 weeks of treatment. The AMBITION and AMAZE programs will both study a subcutaneous maintenance dose of up to 40 milligrams. Next slide, please. We are looking forward to an exciting year across various therapy areas here at Novo Nordisk. Starting with diabetes, as you heard about the advancements made with our late-stage internal assets, CagriSema and zenagamtide. We have also made progress through external innovations over the last few years. We expect Phase II results from our in-licensed UBT251 asset, a GLP-1, GLP/glucagon tri-agonist, in a Chinese type 2 diabetes population in the first half of this year, alongside plans to initiate our own Phase II study in type 2 diabetes in the latter half. Within diabetes-associated comorbidities, we anticipate the first readout of ziltivekimab from the ZEUS Phase III trial later this year, assessing relative risk reduction of 3-point MACE on top of standard care. Ziltivekimab holds promise as a first-in-class treatment targeting systemic inflammation in individuals with atherosclerotic cardiovascular disease and chronic kidney disease. In the area of obesity, we look forward to results from the REDEFINE 4 trial in the first quarter of this year, which is evaluating weight loss efficacy in comparison to tirzepatide, primarily focused on the percent change in body weight for non-inferiority. We are also assessing the further weight loss potential of CagriSema in the ongoing REDEFINE 11 trial, with results expected early in 2027. A new high-dose Phase III trial for CagriSema is set to begin later this year. For our triple agonist, we anticipate Phase II results from our in-licensed UBT251 asset in a Chinese obese and overweight population in the first half of this year and have initiated our own Phase Ib/II study in obesity. Additionally, we completed the first human dose trial with our internal triagonist, targeting GLP-1, GIP amylin, in the third quarter of 2025. We tested single doses up to 1.5 milligrams and weekly subcutaneous doses up to 1.24 milligrams, focusing on treatment-emergent adverse events as the primary endpoint. The safety profile of the triagonist was consistent with incretin-based therapies, with body weight change from baseline ranging from minus 3.6% to 5.3% for the triagonist compared to 0.5% for placebo at 4 weeks, confirming our belief in its potential for significant weight loss efficacy. We have began a Phase Ib/II trial in obesity, with expected results during the first half of 2027. Furthermore, we have multiple ongoing submissions in obesity globally. We anticipate decisions from the EU regarding oral semaglutide 25 milligrams and injectable semaglutide 7.2 milligrams in the latter half of this year. We also expect forthcoming decisions on semaglutide 7.2 milligrams and, later in the year, CagriSema in the U.S. The year 2026 is shaping up to be exciting in rare disease as well, with the Phase III HIBISCUS readout for etavopivat in sickle cell disease expected in the second quarter of this year. Etavopivat has a novel mechanism of action that may enhance both hemoglobin health and reduce vaso-occlusive crisis event rates for individuals with sickle cell disease. Finally, we await regulatory decisions on denecimig, formerly known as Mim8. Denecimig is designed for once monthly, biweekly, or weekly prophylaxis to prevent or decrease the frequency of bleeding episodes in patients with hemophilia A with or without inhibitors. Regulatory decisions in the U.S. and the EU are expected in the latter half of 2026. With that, I will hand it over to you, Karsten.
Karsten Knudsen, CFO
Thank you, Martin. Please turn to the next slide. In 2025, our sales grew by 10% at constant exchange rates, driven by both operating units. In the U.S., sales growth was positively impacted by gross to net sales adjustments. The gross margin decreased to 81% compared to 84.7% in 2024. The decrease in gross margin is impacted by amortization and depreciation related to the acquisition of the 3 Catalent manufacturing sites as well as one-off restructuring costs related to the company-wide transformation we announced in the third quarter. Operating profit decreased by 1% in Danish kroner and increased by 6% at constant exchange rates, reflecting higher sales and distribution costs tied to Wegovy promotional activities and launches as well as increased early research and development stage investments. The main impact on operating profit was, however, the company-wide restructuring cost of around DKK 8 billion. Excluding this, operating profit would have increased by 6% in Danish kroner and 13% at constant exchange rates. Please go to the next slide. In 2025, from a net profit of DKK 102 billion, we generated close to DKK 120 billion in cash from operating activities. Our deployment of capital follows our allocation principles of investing in the business with around DKK 60 billion going towards manufacturing capacity expansion through capital expenditure and around DKK 30 billion to expand the R&D pipeline through business development activities. We also returned around DKK 52 billion to shareholders in the form of dividends. At the Annual General Meeting on March 26, 2026, the Board of Directors will propose a final dividend of DKK 7.95 for an expected total 2025 dividend of DKK 11.70, including the interim dividend paid out in August '25. This is a 2.6% increase compared to last year, making it the 30th consecutive year with increasing dividend per share. Novo Nordisk will continue to deliver returns to shareholders in 2026 with total cash returns anticipated to be over DKK 60 billion. In addition, the Board of Directors has approved a new share repurchase program of up to DKK 15 billion to be executed during the next 12 months. Please turn to the next slide. In 2026, sales and operating profit will be positively impacted by a reversal of sales rebate provisions of USD 4.2 billion related to the 340B Drug Pricing Program in the U.S. In order to enhance transparency and comparability of underlying operating performance, Novo Nordisk will present outlook and expectations on adjusted sales and adjusted operating profit growth basis at constant exchange rates going forward. This is introduced to exclude certain exceptional and nonrecurring effects, primarily of noncash nature, including the provision reversal. Adjusted operating profit will likewise exclude the impact of the 340B provision reversal as well as other exceptional and nonrecurring effects related to effects such as major impairment losses and major legal matters. For 2026, adjusted sales growth is expected to be minus 5% to minus 13% at constant exchange rates. Given the current exchange rate versus Danish kroner, growth reported in Danish kroner is expected to be 3 percentage points lower than at constant exchange rates. The outlook reflects expectations for sales growth within International Operations and expectations for sales decline within U.S. operations. The global GLP-1 market expansion is assumed to continue in 2026, enabling Novo Nordisk to increase patient reach and expand volumes. However, this is countered by lower realized prices, including impacts from the most favored nations agreements in the U.S. and loss of exclusivity for the semaglutide molecule in certain markets in International Operations. Lastly, positive impacts related to U.S. gross to net sales adjustments during 2025 are not anticipated to reoccur. In International Operations, the outlook is based on current growth trends, including continued volume penetration from GLP-1 treatments and market expansion, mainly within obesity as well as intensifying competition and negative impacts from the patent expiry of semaglutide in certain markets. In U.S. operations, the outlook is based on current prescription trends for the injectable GLP-1 portfolio, intensifying competition as well as negative impact from reduced anti-obesity medication coverage in Medicaid. Furthermore, lower realized prices linked to investments in market access are amplified by the MFN agreement with the U.S. administration. Uptake related to the launch of the Wegovy pill is reflected based on a range of assumptions related to market penetration, potential negative impact on the growth of the injectable anti-obesity medication category as well as channel mix. Adjusted operating profit growth is expected to be minus 5% to minus 13% at constant exchange rates. Given the current exchange rates versus the Danish kroner, reported operating profit growth in Danish kroner is expected to be around 5 percentage points lower than at constant exchange rates. The expectation for adjusted operating profit growth primarily reflects the sales growth outlook combined with targeted investments in current and future growth opportunities within R&D and commercial. Other key modeling considerations for 2026 are shown on the slide. Of note, as of 2026, Novo Nordisk defines free cash flow as net cash generated from operating activities less purchase of property, plant, and equipment and is expected to be DKK 35 billion to DKK 45 billion. Capital expenditure is expected to be around DKK 55 billion in 2026. In the coming years, the capital expenditure investments are expected to decline following expansion project finalizations. That covers the outlook for 2026. Now back to you, Mike.
Maziar Doustdar, CEO
Thank you, Karsten. Please turn to the next slide. Our 2025 strategic aspirations have run their course. And while we acknowledge 2025 presented significant challenges affecting our performance and share price, those adversities have also made us more resilient. We have plenty of work left to do in order to meet the vast unmet needs for people living with diabetes, obesity, and their related comorbidities as well as those with rare diseases, which we aim to treat in the future. We expect to introduce new strategic aspirations as part of Capital Market Day, which will be held on September 21 in London. Until then, we will, of course, continue to report and track progress across key dimensions of the business. With that, I will turn it back to you, Michael.
Michael Novod, Head of Investor Relations
Thank you, Mike. Next slide, please. With that, we're now ready for the Q&A. Operator, we're now ready to take the first question.
Operator, Operator
Your first question today comes from James Quigley from Goldman Sachs.
James Quigley, Analyst
I got 2, please. So firstly, just to try to triangulate your guidance. You're suggesting low single-digit growth in International Operations. And again, that would suggest minus 20% also in the U.S. So could you give us a sense of how this breaks down between volumes and price at a high level, please, particularly given that your key competitor suggested low to mid-teens pricing on a global basis this morning? And the second question, on the Medicare unlock, how are you thinking about the potential speed here? Again, your competitors suggest the unlock could be pretty fast starting from July 1. But the guidance certainly suggests slower uptake here. So what are the basis of your assumptions around the speed of unlock?
Michael Novod, Head of Investor Relations
Thank you, James. Two questions, both for Karsten.
Karsten Knudsen, CFO
Thank you, James, and thank you for listening in and posing your question. As to the guidance first, with the International Operations delivering 8% growth in the fourth quarter of last year and around 10% in the second half, that's the run rate we are entering 2026. Then adjust for LOE in specific markets on sema, then you get to mid-single-digit growth for International. And consequently, based on our guidance, the residual leaves the U.S. growth to be in the teens in terms of sales decline. So that's the key factors. I would say the U.S. decline is driven by price declines, and it's driven by both investments in market access being a key driver built off the cash channel in the U.S. at a different price point, so channel mix and then the MFN impact where we announced that it will have a low single-digit impact on group sales, so meaning roughly double on U.S. So the key notion is, of course, with these price reductions, to what extent are we then able to convert that into expanding volume reach and volumes in the marketplace. It's early days. We have built assumptions in. Clearly, we've looked at the first 4 weeks of the Wegovy pill launch, where we're very encouraged, as Dave showed just before. And the same on the Wegovy injectable, we're actually looking at to the tune of 30% of the Wegovy injectable scripts now being cash-driven. So also building that. So we are seeing a volume response to the lower prices. Exactly how the year pans out? It remains to be seen because we have a number of variables at play. But net-net, it is price declines that drive U.S. down.
Operator, Operator
Your next question today comes from the line of Sachin Jain from Bank of America.
Sachin Jain, Analyst
I've got 2 more on guidance, if I may, Karsten, and apologies. So maybe framing James' question slightly differently. I asked the pushes and pulls question at the third quarter, and not without misspeaking, but I think you roughly phrased as underlying growth less 3 sets of headwinds or roughly low single digit each. So I'm just trying to understand between 3Q and the guidance today, what shifted you from that sort of low single digit to now minus 5% to 13%. So the mid- to high single-digit delta versus consensus, how much of that is volume and price? And within price, what's the new component, it seems to be cash channel? And then second, more specifically, a question I had frequently overnight is what needs to happen for you to achieve the bottom end of your guidance?
Michael Novod, Head of Investor Relations
Thanks, Sachin. Also 2 questions for Karsten on guidance and also on the sort of push and pull between high and low.
Karsten Knudsen, CFO
Thank you for your questions, Sachin. As you may remember, I did not provide guidance for 2026 during our Q3 call, which is an important point to start from. In our current release, we emphasize that our guidance is shaped by the most recent market trends. The guidance we are issuing now reflects the current run rate we are observing in the market based on Q4 performance, as I mentioned earlier, along with relevant events, expectations, and assumptions about the future. These are the main factors we considered. Compared to what we knew in Q3, we now have more insights into the run rate in International Operations, including the 8% growth in the fourth quarter. Additionally, we have gained more information on specific pricing and reimbursement decisions in certain markets. In the U.S., beyond what we learned from closing out Q4, we are pleased with how the Wegovy pill has been received in its first month, as Dave mentioned, as well as the performance of the Wegovy injectable cash business following the reduction in initiation prices to $199. These are the significant changes we've seen since three months ago.
Michael Novod, Head of Investor Relations
High, low?
Karsten Knudsen, CFO
Thanks, Michael, for bringing that up. It's important to note that we've seen this trend for several years. The obesity market is much more dynamic compared to other markets, which often have more stable prescription trends through general practitioners. The overall market conditions can have both positive and negative effects, especially in the obesity sector. We are not worried about market growth; we observed it more than double in 2025, and we are confident that it will continue to expand. However, the variables I mentioned include competitive dynamics, ongoing gross to net trends that are forecasted with some delay, and how sourcing and channel dynamics affect the pricing and volume of the Wegovy pill and its relationship with the Wegovy injectable, as well as how competitive launches may influence the market. These are typical factors, but they play out in a very dynamic segment.
Operator, Operator
Your next question comes from the line of Richard Vosser from JPMorgan.
Richard Vosser, Analyst
Just one follow-up, thinking about formulary access for Wegovy. You highlighted the access for oral Wegovy in a pill. But how are you seeing and how you're thinking about that access in the commercial channel this year? It seems like maybe employers would be incentivized to maybe reduce access given the availability of products in the cash channel at lower prices. So just thoughts on that and how that might affect the mix and volumes in that channel. And maybe a second question, just compounder volume. Obviously, a very strong oral launch, and you're saying new patients. But any evidence that those lower prices are stymying the compounder volume and any idea that you're taking share using the oral from compounders?
Michael Novod, Head of Investor Relations
Thanks, Richard. So 2 questions for Dave. One on the formulary access and also the other one on compounder.
David Moore, EVP, U.S. Operations
Yes. Thanks very much, Richard. On the injectable side, we see relatively stable access. And of course, we have discussions every year to maintain that level of access. And as you've heard us talk about before, we're very interested in reducing that friction and making the experience easier for patients. We did have some states that have decided to not cover AOMs, for example, California is a big one. But I will say that with the lower prices that are available today, we will continue to reengage with those states with the hopes that we can increase access in Medicaid as well. On the pill side, what you heard me mention is we've actually seen some positive progress in just the first month. We started out the month of January having CVS covering it right out of the gate. And then we quickly were able to add Prime, Optum, and Anthem, and we will continue to build that over the course of the year, expecting that there will be both plans as well as employers that will be interested in covering the pill. On your second question about compounding, we haven't seen a change yet. It's early days. The compounding market, what we're seeing right now is what we would consider relatively stable. I can tell you, as of this week, we have over 170,000 people that are on the Wegovy pill, and most of that is self-pay. And we get daily feeds because of the way that we went to market. And so we certainly expect that there could be some switching that's coming from compounding, but it's a little bit early to tell, and we don't get any of that longitudinal data, but we'll certainly be researching that as more data comes in.
Operator, Operator
Your next question comes from the line of Peter Verdult from BNP Paribas.
Peter Verdult, Analyst
Peter Verdult, BNP. Two questions. Just firstly, on Martin, I realize you're not going to change the messaging on REDEFINE 4 at this juncture. But can you at least remind us on trial design? Was flexible dosing allowed as we saw in REDEFINE 1? Or is it more fixed in nature for CagriSema and tirzepatide in REDEFINE 4? Basically, any major trial differences we need to be aware of when we compare REDEFINE 4 to 1? And then Karsten, Mike, forgive me going back to guidance, but I'm not going to ask you to go line by line every assumption. But just the spirit of the guidance you provided, I mean, is this reflecting sort of genuine concerns on cannibalization and competition? Or are you simply starting the year as conservatively as you can to finally prevent this persistent earnings downgrades story from continuing through 2026?
Michael Novod, Head of Investor Relations
Thank you, Pete. So two questions. First, to Martin on REDEFINE 4. And then second to Mike, on high-level guidance dynamics.
Martin Lange, EVP, Research and Development
Absolutely. So REDEFINE 1, you're absolutely right. We basically have no new news. So we're not going to change the story. REDEFINE 4 is comparing CagriSema and tirzepatide in an obese population on weight loss testing for non-inferiority first, followed by superiority testing. The dosing was similar to REDEFINE 1. As you recall, we took some learnings from REDEFINE 1, including that we needed to do longer studies. And I think we maintain what we've always said for REDEFINE 4, but we also are looking forward to REDEFINE 11, where we'll see the full weight loss potential of CagriSema.
Maziar Doustdar, CEO
Very good. So Peter, I think I'll start by saying we have all acknowledged how volatile and dynamic the obesity market is with a lot and lots of moving parts. The way we guide is we discuss and talk, of course, to our operating units. We take a look at the macro trends, and we put the latest information we have in place. We start by looking at the last year's finish and the run rate to that, especially Q4, but even more so granularly looking at the 3 months within the Q4 data that we have available. So that's kind of a starting point. Then we basically go ahead and try to see the new data we have available. Karsten alluded to it. We have 4 weeks of pill data. It's incredibly encouraging, and we consider that. And it's in the guidance basically. Of course, not fully knowing what's going to happen in the next 11 months, but we make some good assumptions around that. Then there are things that we have actually previously discussed with all of you. Think about the LOE in International Operations. That hasn't really changed. It was there before. It is now. We have not seen the impact of that yet. It will come into place starting from Q2. And so will some of the other things on the upside that will come in, in Q2. We just touched upon it, Medicare is a group of people that we would love to provide GLP-1 products to, but we haven't started yet, and it's going to basically get going in the second part of the year. So we make assumptions around that. We put the midpoint and our own targets, and then we give it the plus and minus the 4 points on each side. And that's how we've done it in the past. That's how we've done it this year.
Operator, Operator
Your next question comes from the line of Michael Nedelcovych from TD Cowen.
Michael Nedelcovych, Analyst
I have 2 questions. My first is on Wegovy pill supply. Given the strong launch of Wegovy pill, is there any risk of supply outages in 2026? For example, if adoption persists at this current high level, could Novo service that demand through the end of the year with its current capacity? And then my second question is on CagriSema and REDEFINE 4. Martin, I have to admit your response to the earlier question struck me as somewhat ominous. Why do you think we will have to wait for REDEFINE 11 readout to see the full weight loss potential of CagriSema? Why could it not be revealed by REDEFINE 4 given the changes that were made to the trial?
Michael Novod, Head of Investor Relations
Thank you very much. Two questions. First, to Mike on the Wegovy pill supply and the second one to Martin on both REDEFINE 4 and REDEFINE 11.
Maziar Doustdar, CEO
Yes. Thanks very much, Mike. Over the last period, on a number of occasions, I have spoken to how confident we are with regards to the Wegovy pill supply. We basically have said that we launched the pill in the U.S. at a time where we will be confident enough to know we will not run into supply situation anymore. We have seen an incredible uptake, I would say, in the first month. And today, I will reaffirm to you that we feel incredibly confident that we will be able to supply the U.S. market.
Martin Lange, EVP, Research and Development
Yes. On REDEFINE 4, we always have to think about when we do amendments to ongoing trials, we cannot fully guide what will happen. We can extend the study. But we also had to acknowledge that the learnings that we took from REDEFINE 1 was in part, we needed to do longer treatment duration. But it was actually also paradoxically in part to drive even more flexible dosing, securing that we actually get more patients to the highest target, but using longer time. That we cannot change in REDEFINE 4. We have optimized that in REDEFINE 11. So the trial duration, we have tried to optimize in REDEFINE 1. But in REDEFINE 11, we have taken all the learnings on titration, what we call flexible titration. I'm not sure I still like the word, but what we call flexible titration and put that to use in REDEFINE 11. And we can already now see that, that does really make a difference to the patients and how they act in the trial. So I still have a lot of optimism on REDEFINE 4, but I think the full weight loss potential, we will only learn when we do the full trial duration and the flexible dosing that really will drive patients to use CagriSema in the optimized way.
Operator, Operator
Your next question comes from the line of Harry Sephton from UBS.
Harry Sephton, Analyst
I have 2 on the Wegovy pill, please. Just want to start with what your expectations are for the sustainability of the Wegovy pill demand. If you wouldn't mind, is there any evidence from Novo's Rybelsus experience that points to any variation in the stay time on therapy versus the injectable? And how you think about also the demand for the pill through the competitor orforglipron launch? And then my second question is on the economics of the Wegovy pill. So given the much lower price point and the much higher API demand, how does the gross margin contribution of the Wegovy pill compare to the injectable?
Michael Novod, Head of Investor Relations
Thank you very much, Harry. Two questions. The first on the Wegovy pill demand and dosing to Mike. And then the second one around economics to Karsten.
Maziar Doustdar, CEO
Thank you very much. When considering the sustainability of growth and demand, two things come to mind. First is the competitive pressure and how much we push ourselves despite that competition. We've fully committed to this, and our launch has been exceptional, in part because of the extensive activities and promotions we've implemented. A significant factor in our success has been our partnerships with e-Health providers, which has allowed us to be present in 70,000 retail pharmacies. However, the important question is what happens when competition enters the market. Can we maintain this momentum? Is it sustainable? The past two years in the obesity market have taught us something important: the primary factor for patients choosing anti-obesity medication is the amount of weight loss. Our latest trial indicates that Wegovy leads to a 16.6% weight loss, along with cardiovascular benefits. In comparison, data from a competing product shows a weight loss of 12.4%. If you look at these numbers, it’s clear that patients would prefer a 17% weight loss over 12%. We've seen this reflected in the rapid uptake from 170,000 employees who understand that this isn't just a pill; it's a peptide, a larger protein within a pill that delivers significant effectiveness. This gives us great optimism, and we will keep promoting it vigorously. Don't be surprised if you see our presence during the big game on Sunday as we strive to ensure the success of this pill.
Karsten Knudsen, CFO
Thanks, Harry, for the manufacturing economics question. On gross margin, the short version is that the gross margin on the Wegovy pill is below that of the Wegovy injectable, but it's important to know that it's lower on gross margin level, but it's still an attractive gross margin. So we are all in pushing the pill. And of course, the overarching intention is to expand the markets and not cannibalize from our own products.
Operator, Operator
Your next question comes from the line of Thibault Boutherin from Morgan Stanley.
Thibault Boutherin, Analyst
First question is about Ozempic and the timing for the implementation of the MFN price. When will the MFN negotiated price take effect for Medicare and Medicaid this year? Is there any expected increase in volume since it is already covered, or should we anticipate a loss in market share that could negate the benefits? The second question, directed to Martin, is regarding the Wegovy pill. To understand adherence better, could you explain what happens to a patient who misses a pill for a day or two? How does that affect weight loss efficacy? Additionally, if a patient is on the highest dose and misses a few pills, can they resume at 25 milligrams? Also, what do the side effects look like?
Michael Novod, Head of Investor Relations
Okay. Two questions. First on Ozempic and MFN for you, Dave. And then the second question for you, Martin.
David Moore, EVP, U.S. Operations
Yes. Thank you, Thibault. With respect to Ozempic, as you know, we have Medicare coverage right now in the diabetes. And so with respect to MFN as well as MFP. That's more of a 2027 event. Of course, we did make Ozempic available in self-pay. As I mentioned, we're seeing about 8,000 scripts a week now in self-pay for those patients that don't have coverage. But the MFN and MFP is more of a 2027 event.
Martin Lange, EVP, Research and Development
Yes, absolutely. On the Wegovy pill, we do know that in general, when patients are on chronic treatment, sometimes they skip a dose. It is important to remind ourselves that semaglutide is semaglutide and the half-life of semaglutide once in steady state is very long, basically, as you know, also in the subcutaneous state, allowing for once-weekly doses. That basically means that when you are on a stable dose on the Wegovy pill and then you skip a dose, it doesn't have a huge impact on your blood exposure in that period of time. And you can also then reinitiate at the 25-milligram dose without experiencing any untoward effects. So from that perspective, semaglutide is semaglutide, and we are benefiting from the long half-life of semaglutide also in the oral delivery. Other orals would have with shorter half-life a much different profile because that will both impact the potential efficacy, but also the potential tolerability if you skip 1 or 2 doses.
Operator, Operator
Your next question comes from the line of Carsten Lombard Madsen from Danske Bank.
Carsten Madsen, Analyst
In terms of CapEx, where again this year guide for a relatively high CapEx level in terms of billions being spent. Can you confirm that the API build-out is on track because it feels like this entire program is taking longer and is being much more expensive than what we expected some years ago? And secondly, on the high doses Wegovy approval, which we hopefully see soon, also will you be launching immediately? Can you confirm that? And in which type of pill will you be launching?
Michael Novod, Head of Investor Relations
Thank you, Carsten. And first, on CapEx to Karsten and then the second question on 7.2 to Mike.
Karsten Knudsen, CFO
Yes. Thank you for that question, Carsten. And as I said earlier on, then we are moving downwards in terms of CapEx. This is the first step down, and then we expect to see a steeper slope in the coming years. And it really links to finalization of projects approved in prior years. As it is with projects, some are ahead, some are behind. But in the broad scheme, we are on track. Specifically for API, we do expect to have some of the new major API facilities online already this year and more to come in the coming years.
Maziar Doustdar, CEO
Regarding the 7.2 Wegovy high dose, we filed under the CNPV voucher program in December last year and announced that we expect approval this quarter. Once we receive that approval, we will launch immediately. It's crucial for everyone to understand that dosage impacts the effects of medicine. Currently, semaglutide at 2.4 milligrams leads to a 15% to 16% weight loss, while tirzepatide at 15 milligrams results in 20% to 21%. Our step-up data indicate that increasing semaglutide to 7.2 brings its effectiveness close to that of tirzepatide. This understanding is vital as it highlights that alongside comparable weight loss, there are cardiovascular, kidney, and liver benefits to consider, allowing people to make informed choices. Thus, we are fully committed to this launch, which will utilize the same type of devices we currently have available to start.
Operator, Operator
Your final question for today comes from the line of Simon Baker from Rothschild & Co.
Simon Baker, Analyst
I have two quick questions. First, regarding the guidance that has been frequently discussed, would it be accurate to say that the high visibility on price impact combined with low visibility on volume uplift is a key factor reflected in your guidance? Secondly, could you provide an update on your assumptions regarding generic competition in IO, particularly in Canada? I ask this because we've heard that all the semaglutide generics received notices of deficiency from Health Canada, and the expectation is that these issues won't be resolved until mid-year. Therefore, it seems that generic semaglutide in Canada will impact the second half of the year rather than the first half. I would like to know your thoughts on this and to what extent it might be reflected in the guidance.
Michael Novod, Head of Investor Relations
Two questions, more or less boiled down to one on the guidance dynamics again, Karsten.
Karsten Knudsen, CFO
Thank you, Simon, for your questions. For our mature reimbursed brands, we have established trends for volume, measured as TRx, and we feel confident about the contracted prices. This aspect is fairly straightforward. The uncertainty lies in the self-pay channel, particularly with price elasticity, which we are still assessing. As Dave mentioned earlier, we have seen great initial uptake of the Wegovy pill in the first four weeks, but the obesity self-pay segment is very dynamic. It's unclear how this will evolve throughout the year, with factors like seasonality, sourcing, and competition impacting it. We make our best assumptions, but there could be both positive and negative outcomes, which is why we provide a range. Concerning Canada, as we stated in previous quarters, the loss of exclusivity for semaglutide in international markets will have a low single-digit impact on group sales, with Canada being the largest contributor. We have factored in the timing of generic approvals and launches, although we lack detailed insights on their progress. Time will significantly affect this impact. While we believe the overall direction remains consistent, there could be both upside and downside risks to our guidance, depending on how quickly generics are approved in Canada. We will have to wait and see.
Michael Novod, Head of Investor Relations
Great. Thank you, Karsten. Thank you, Simon. This also concludes the Q&A session. Thank you for participating, and please feel free to contact Investor Relations regarding any follow-up questions you might have. Before we close the call, I would like to hand over to you, Mike, again for the final remarks.
Maziar Doustdar, CEO
Thank you very much, Michael. I want to start by thanking Ludovic and Dave for all you have done for Novo Nordisk over the many, many years. I also want once again to welcome Jamey and Hong and stress that I'm looking very much forward to working with both of you. 2026 will be basically a year where we will face some headwinds, especially on the back of the price declines, and we have shown that in our guidance today. But I'd also like to say that price reduction in some ways is our investment for the future and for capturing more patients. Perhaps no other company better than Novo Nordisk is geared in improving health at scale within the field of diabetes and obesity, and we're ready to do that. And I believe much stronger than with affordable prices, we can get to those higher volumes faster. We are looking very much forward, of course, as we go forward to share more information with you, not least about the continuous uptake of the phenomenal Wegovy pill success that we have seen, but maybe also much more exciting readouts and regulatory milestones throughout the year across all of our therapy areas. With that, I'd like to thank all of you for joining us today. Thank you.
Operator, Operator
Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.