Novo Nordisk A/S (NVO) Q4 2025 Earnings Report, Transcript and Summary

Good day, and thank you for standing by. Welcome to the Q4 2025 Novo Nordisk Earnings Conference Call. [Operator Instructions] 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.

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.

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 therapeutical 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 -- would mean for people living with obesity. We are treating nearly 46 million people with our innovative medicines, reflecting Novo Nordisk 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 the 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 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 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 life cycle 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 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.

Thank you, Mike, and please turn to 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 milligram for weight loss and Ozempic 2-milligram 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.

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 now 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 has 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 milligram 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.

Thank you, Dave. Please turn to the next slide. This week, we announced the top line readout from REIMAGINE 2, a Phase III trial for CagriSema in type 2 diabetes. The trial included around 2,700 people with type 2 diabetes inadequately controlled with metformin with or without an SGLT2 inhibitor. People were randomly assigned to receive either CagriSema 2.4 milligram or 1 milligram, semaglutide 2.4 milligram or 1 milligram or cagrilintide 2.4 milligram or placebo. The study assessed superiority of CagriSema versus Semaglutide on A1c as the primary endpoint with change in body weight as one of the secondary endpoints. Approximately 40% of all participants were using an SGLT2 inhibitor before initiating the trial. Please go to the next slide. In Reimagine 2, CagriSema 2.4 milligram demonstrated superior A1c reduction and weight loss versus semaglutide 2.4 milligram. Assuming all people adhere to treatment and from a mean A1c baseline of 8.2%, CagriSema 2.4 milligram achieved a superior A1c reduction of 1.91 percentage points. This is compared to 1.76 percentage points with semaglutide 2.4 milligram. In addition, CagriSema 2.4 milligram achieved a superior weight loss reduction of 14.2%. More than 40% of the participants treated with CagriSema 2.4 milligram achieved over 15% weight loss and around 1 in 4 achieved over 20% weight loss. In the trial, CagriSema appeared to have a safe and well-tolerated profile. The most common adverse events were gastrointestinal with the vast majority being mild to moderate and decreasing over time. This data is in line with the recent top line readout of REIMAGINE 3 with CagriSema as an add-on to basal insulin. In that study, people treated with CagriSema 2.4 milligram achieved an A1c reduction of 2.33 percentage points and a weight loss of 12% at 40 weeks, all superior to placebo. Results from the pivotal REIMAGINE 1 trial are anticipated in the first quarter of 2026. In addition, we await the long-term safety and efficacy cardiovascular outcomes trial, REDEFINE 3. Following these results, Novo Nordisk will approach authorities to discuss the regulatory pathway for CagriSema in type 2 diabetes. In summary, CagriSema has demonstrated superior results in both glycemic control and weight reduction. These results represent a highly effective treatment option for individuals with type 2 diabetes seeking weight management solutions in addition to glycemic control. Next slide, please. In November, we announced positive headline results from the first evaluation of zenagamtide, formerly called amycretin in people with type 2 diabetes. The trial investigated the efficacy, safety and pharmacokinetics of once-weekly subcutaneous and once-daily oral zenagamtide compared to placebo. The trial included around 450 people with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor, a standard of care. About 40% of participants were using an SGLT2 inhibitor at baseline. The trial was a combined multi-ascending dose study investigating 6 subcutaneous doses ranging from 0.4 milligram to 40 milligram and 3 oral doses ranging from 6 milligram, 25 milligram to 50 milligram. From a mean baseline 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 people adhere to treatment. The proportion of people achieving A1c below 7% was up to 89.1%. Furthermore, people treated with oral zenagamtide achieved dose-dependent reductions of A1c of up to 1.5 percentage points by week 36 from a baseline of 8%. Almost 78% of people achieved an A1c level below 7%. The estimated improvements in A1c were all statistically significant versus placebo, confirming the primary endpoint in the trial. Both subcutaneous and oral zenagamtide appear to have a safe and well-tolerated profile, consistent with other incretin and amylin-based therapies. The data further support the potential of zenagamtide as a next-generation treatment for type 2 diabetes, and we look forward to bringing it into an extensive Phase III program called AMBITION in type 2 diabetes and other indications in the second half of 2026. In addition, the Phase III obesity program called AMAZE will start in the first quarter of 2026. As a reminder, the Phase Ib/IIa clinical trial with incretin in people with obesity or overweight demonstrated a 22% weight loss with a 20-milligram dose after 36 weeks of treatment. The AMBITION and the AMAZE programs will both investigate the subcutaneous maintenance dose up to 40 milligrams. Next slide, please. We have an exciting year ahead across therapy areas here at Novo Nordisk. Beginning with diabetes, you just heard about the advances that we made with our late-stage internal assets, CagriSema and zenagamtide. We've also achieved progress through external innovation that we have done throughout the last few years. We expect Phase II data 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 with plans to initiate our own Phase II study in type 2 diabetes in the second half of this year. Within the diabetes associated comorbidities, the first readout of ziltivekimab from the ZEUS Phase III trial is anticipated in the second half of this year. The trial is assessing 3-point MACE relative risk reduction on top of standard of care. Ziltivekimab holds the potential to be a first-in-class treatment targeting systemic inflammation in people living with atherosclerotic cardiovascular disease and chronic kidney disease. In obesity, we expect results from the REDEFINE 4 trial in the first quarter of this year, assessing weight loss efficacy compared to tirzepatide. The study's primary endpoint is percent change in body weight assessed for non-inferiority. We are assessing further CagriSema weight loss potential in the ongoing REDEFINE 11 trial with the results expected early in 2027. And new Phase III trial with CagriSema high dose is also planned to initiate later this year. For our triple agonist, we expect Phase II data from our in-licensed UBT251 asset in a Chinese obese and overweight population in the first half of this year, and we have already initiated our own Phase Ib/II study in obesity. We would also like to highlight the first human dose trial with our internal triagonist, GLP-1, GIP amylin targeted agonist that was completed in the third quarter of 2025. Single doses up to 1.5 milligram and multiple weekly subcutaneous doses up to 1.24 milligram were tested. The primary endpoint was treatment-emergent adverse events. The safety profile of the triagonist was consistent with incretin-based therapies. The percentage change in body weight from baseline range from minus 3.6% to 5.3% for the triagonist versus 0.5% for placebo at 4 weeks. The 4-week data confirm our belief in the potential for high weight loss efficacy with the triagonist. We recently initiated a Phase Ib/II trial in obesity with expected readout during the first half of 2027. In addition, we have several ongoing submissions in obesity in the U.S. and globally. We anticipate the EU's decision on oral semaglutide 25 milligram and injectable semaglutide 7.2 milligram during the second half of this year. We also anticipate forthcoming decisions regarding semaglutide 7.2 milligram and later in the year, CagriSema in the U.S. 2026 is an exciting year in rare disease as well. The Phase III HIBISCUS readout for etavopivat in sickle cell disease is expected in the second quarter of this year. Etavopivat has a novel mechanism of action with the potential to improve both hemoglobin health and vaso-occlusive crisis event rates in people living with sickle cell disease. Finally, we are awaiting regulatory decision for denecimig previously known as Mim8. Denecimig is a once monthly -- once every 2 weeks or once-weekly prophylaxis treatment to prevent or reduce the frequency of bleeding episodes in people with hemophilia A with or without inhibitors. Regulatory decisions in the U.S. and the EU is expected in the second half of 2026. With that, over to you, Karsten.

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.

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 adversaries 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 treat -- 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.

Thank you, Mike. Next slide, please. With that, we're now ready for the Q&A. [Operator Instructions] Operator, we're now ready to take the first question.

[Operator Instructions] And your first question today comes from the line of James Quigley from Goldman Sachs.

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 [ further ] 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?

Thank you, James. Two questions, both for Karsten.

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, then 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, a few quarters ago or 1 quarter ago, 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. On Medicare and impact from Medicare Part D and the MFN deal, we do expect that we'll have a benefit starting around mid this year, having Wegovy reimbursed in Medicare Part D and hence, being available for seniors under reimbursed setting. We have included that in our guidance. But at this point, given the lag times of educating physicians and physicians and admin staff understanding how it works and for patient to access that benefit, it will be a gradual ramp with limited benefit this year and a bigger benefit into 2027.

Your next question today comes from the line of Sachin Jain from Bank of America.

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? Multiple investors trying to work out how conservative that is, particularly around your oral assumptions being driven by injectable switch.

Thanks, Sachin. Also 2 questions for Karsten on guidance and also on the sort of push and pull between high and low.

Yes. Thanks for these questions, Sachin. And as you recall, I didn't guide for 2026 at our Q3 call. So that's a starting point. And as we also note in our current release, we base our guidance based on the latest trends we see in the market. So the guidance we put out now is based on, of course, the run rate we left 2025 with. So Q4 performance, as I alluded to before, and then whatever triggering events and expectations and assumptions around the future we are building in. So those are really the key points that we built in. What have we known -- what do we know more today compared to Q3? We have some more nuances on the run rate in International Operations. You see the 8% growth in the fourth quarter. And of course, some more market intel on more specific and detailed pricing and reimbursement choices in some of the markets there. And then in the U.S., what we know there beyond the Q4 closeout was -- is really about, I would say, the Wegovy pill uptake in the first month, as Dave alluded to, which we're very happy with, and then the Wegovy injectable cash business and the response to the lowering of the initiation prices to $199. So that's really kind of the key fundamental changes since 3 months ago.

High, low?

Thanks, Michael, for reminding me on that one. It's important to remember, and we've been experiencing this for some years now. The obesity market is just significantly more dynamic than most other markets where it's much more stable prescription trends through normal GPs. So the macro variable that can both be positive and negative is the dynamics in the obesity market. It's -- we are not concerned about the expansion of the market. We saw it more than double in 2025. So we're very confident in continued expansion of the market space. But the variables I'm alluding to is really, of course, as always, competitive dynamics, as always, gross to net dynamics that are being forecasted with a lag. And then also the sourcing dynamics and channel dynamics impacting pricing and volume of Wegovy pill and how that is impacting both Wegovy injectable, but also how a competitive launch plays into all of this. So I'd say it's classic variables, but it's in a very dynamic market segment.

Your next question comes from the line of Richard Vosser from JPMorgan.

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 styming the compounder volume and any idea that you're taking share using the oral from compounders?

Thanks, Richard. So 2 questions for Dave. One on the formulary access and also the other one on compounder.

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 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.

Your next question comes from the line of Peter Verdult from BNP Paribas.

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 downgrade story from continuing through 2026?

Thank you, Pete. So two questions. First, to Martin on REDEFINE 4. And then second to Mike, on high-level guidance dynamics.

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.

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. 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.

Your next question comes from the line of Mike Nedelcovych from TD Cowen.

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?

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.

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.

Very clear.

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.

Your next question call from the line of Harry Sephton from UBS.

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?

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.

Thanks very much. When you think about the sustainability of a growth and demand, then 2 things comes to my mind. One, of course, competitive and competitive pressure as well as how much you push yourself into doing something despite the competitors. Let me start with the first one. We have gone all in. This has been the best launch, partially also because we have really put in all the activities and the promotions that we could think of, not least, of course, what it was alluded to earlier on, the partnership with all of our e-Health players being available in 70,000 retail pharmacies today has been partially due to that -- has been partially the reason behind that incredible uptake. But then, of course, the question comes, what happens after competition arrives? Can you uphold this? Is it sustainable? I would say that the last 2 years has taught us something very specific with the obesity market. It has taught us that the #1 criteria for a patient picking up anti-obesity medication is the magnitude of weight loss. And when you take a look at this, then you realize based on our latest trial, we have shown that when you take the drug, then Wegovy pill gives you 16.6% weight loss in addition to all the CV benefits and the great stuff that it has, with 16.6% weight loss. We've also read the data from our competing product, and we have seen that they are at 12.4%. If you round those things up, then you get to 17% and 12%. If you ask pretty much any patients and certainly ask me, which one would you rather take losing 17% weight loss or 12%, I know my answer. And we have seen the answer from 170,000 employees coming on very quickly, recognizing that this is not just a pill. It's a peptide. It's a large protein inside a pill that gives you that incredible efficacy. And that has been giving us a lot of optimism, and we will continue, of course, pushing this through and promoting it. Don't be surprised if you've seen the big game on Sunday, you see us visible. And we will basically make sure that we'll do our utmost to make this pill a success.

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.

Your next question comes from the line of Thibault Boutherin from Morgan Stanley.

First question, just on Ozempic and the timing of implementation of the MFN price. When does the MFN negotiated price kick in for Medicare and Medicaid this year? And is there any associated volume uplift given it's already covered? Or should we expect market share loss to sort of erase the benefit? And then just the second question, I guess, for Martin on the profile of Wegovy pill. Just in order to understand the adherence, could you help us with what happened to a patient if they miss the pill for a day or a couple of days? How does that impact efficacy in terms of weight loss? And then similarly on tolerability, if a patient is in the highest dose and for some reason, miss a few days of pill, can they go back and resume on 25 milligram? And what -- how do side effects look like?

Okay. Two questions. First on Ozempic and MFN for you, Dave. And then the second question for you, Martin.

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.

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 untowards 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.

Your next question comes from the line of Carsten Lombard Madsen from Danske Bank.

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?

Thank you, Carsten. And first, on CapEx to Karsten and then the second question on 7.2 to Mike.

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.

And Carsten, with regards to the 7.2 Wegovy high dose, then as you know, we have filed in December last year under the CNPV voucher program. And we have announced that we should expect the approval, hopefully, in this quarter. As soon as we get the approval, we are ready to launch. So we will not sit on that regulatory approval. And we will go all in again because I think this is really, really important that the world a little bit understands that medicine is dosed differently. And depending on how you dose things, you get different effect of it. And right now, semaglutide at 2.4 milligram is giving us 15%, 16% weight loss. Tirzepatide at 15-milligram dosing gives you 20%, 21%. We have shown in a step up that when you increase the dose of sema to 7.2, you get very close on par with tirzepatide. And I think it's actually very important that the world gets to know this and then they can judge that on top of on par weight loss, you have also CV benefit, kidney benefits and liver benefits and then people can pick and choose which option they want. So it's very important that we go all in with that, and we're planning to do so. And we will actually -- I think there was a question, and we will launch it in the same type of devices that we currently have available to start with.

Your final question for today comes from the line of Simon Baker from Rothschild & Co.

Two quick questions, if I may. The first one really is just going back to the guidance question that's been repeatedly asked. Conceptually, would it be fair to say that because you have high visibility on price impact and low visibility on volume uplift. That is one of the things -- key things that is reflected in your guidance. And the sort of second part that's related to that. I just wonder if you could update us on your assumptions for generic competition in IO, specifically Canada. The reason I ask is we understand that all of the semaglutide generics have had notices of deficiency slapped on them by Health Canada and the expectation is they will not resolve until the midyear. So generic semaglutide in Canada is a 2H rather than a 1H phenomenon. I'd be interested to get your thoughts on that and the extent, if any, to which that's reflected in the guidance.

Two questions, more or less boiled down to one on the guidance dynamics again, Karsten.

Yes. So Simon, thanks for these questions. Whether -- how -- we detailed build it, I would say for mature reimbursed brands, I think they are very mature established trend lines for volume trends measured as TRx, and we have a good feeling for the prices being contracted, et cetera. So for our mature reimbursed brands, that's -- I'd say that's reasonably straightforward. For where we see the uncertainty is, how can I put it in the self-pay type channel because the price elasticity in the self-pay channel is something that we are still exploring. And as Dave was covering before, then we've seen a fantastic uptake of the Wegovy pill here in the first 4 weeks. But we also know that obesity self-pay is a super dynamic segment. So exactly how that works across the year, to what extent there are seasonalities, et cetera, stay time, sourcing, cannibalization, competition. Clearly, there are uncertainties there. And we put our best assumptions in. And they -- it can go both ways. We can both have an upside and a downside, and that's why we work with the range. For Canada specifically, and in our guidance, as we said in prior quarters that sema LOE in international markets will impact group sales by low single digits. Canada is the biggest contributor. And of course, we put in assumptions around timing of generic launches, approvals and launches. We don't have detailed insights into the status of those files and remediation of these notices of deficiencies. But obviously, time is a key variable in terms of impact. I think the direction of travel is the same, but there could be both an upside and a downside to our guidance depending on the pace of approval of generics in Canada. So remains to be seen.

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.

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 guys for joining us today. Thank you.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.