Novo Nordisk's 2025 was a trying year. The formidable rise of Eli Lilly has left the former metabolic kingpin feeling its foundations shake for the first time on the very battlefield it pioneered.

Eli Lilly demonstrated through head-to-head clinical trials that tirzepatide is significantly superior to semaglutide in weight loss efficacy, subsequently overtaking Novo Nordisk. Market data shows that Lilly's share of total prescriptions in the U.S. incretin analog market has reached 53.3%.

Novo Nordisk responded with an emergency leadership change. The new CEO, Mike Doustdar, initiated the largest layoffs in the company's history in an effort to shed the label of being "conservative and slow." However, can this radical restructuring turn the tide?

At the eleventh hour of 2025, Novo Nordisk scored a crucial victory in its "darkest hour": the oral version of Wegovy (once-daily semaglutide 25mg tablet) received FDA approval, becoming the world's first oral GLP-1 receptor agonist approved for weight management.

The advent of oral weight-loss drugs has rewritten the market's rules. Oral formulations eliminate the need for cold chain logistics and offer overwhelming advantages over injectables in terms of patient adherence and convenience, making the "oral race" the new focal point of competition in the weight-loss drug arena.

IQVIA has dubbed 2026 as "The Year of Orals." Goldman Sachs analysis predicts that by 2030, oral weight-loss drugs will capture 24% of the market, representing a $22.3 billion opportunity.

Launched on January 5, 2026, oral Wegovy reached approximately 50,000 total weekly prescriptions by January 23rd. Its smooth launch was significantly aided by the availability of a 1.5mg starting dose through self-pay channels.

Although Novo Nordisk has again taken a lead in oral formulations, Eli Lilly's counteroffensive is already poised.

Late last year, Eli Lilly submitted its New Drug Application (NDA) for orforglipron. Supported by a Comprehensive National Priority Voucher (CNPV), the drug's review timeline could be compressed from the typical 10-12 months to just 1-2 months, positioning orforglipron for a potential launch in the first half of 2026.

Unlike Novo Nordisk's peptide-based path, Eli Lilly's oral candidate, orforglipron, follows a small-molecule chemical synthesis route, which may offer advantages in production and cost control. Furthermore, compared to oral Wegovy, orforglipron has fewer usage restrictions.

In September 2025, Eli Lilly released results from a head-to-head study comparing orforglipron to oral Wegovy in patients with type 2 diabetes. The data showed orforglipron outperformed its rival in both blood sugar control and weight loss.

For the key glycemic control metric (HbA1c reduction), the highest dose of orforglipron achieved a 2.2% reduction, compared to a 1.4% reduction for the highest dose of oral Wegovy.

Regarding weight loss, direct comparison data is still limited. In the orforglipron trial, the 12mg group achieved an average weight loss of 6.7% (6.6 kg), and the highest dose (36mg) group reached 9.2% (8.9 kg). In contrast, the highest dose (14mg) of oral semaglutide (used in the oral Wegovy development program) resulted in 5.0 kg (5.3%) weight loss.

However, in Novo Nordisk's pivotal Phase III trial OASIS 4 for oral Wegovy, when the dose was increased to 25mg, it demonstrated an average weight loss of 16.6%.

Perhaps more critically, Eli Lilly is preparing proactively, ramping up production facility construction in Texas, Alabama, and Puerto Rico. This showdown is not merely a race to market launch; it is a comprehensive competition encompassing production capacity reserves and supply chain stability.

The oral battle has only just begun. Whether Novo Nordisk successfully regains ground or Eli Lilly once again surges from behind to expand its lead remains to be seen.

Top players never obsess over minor territorial losses at the edges of the board. While the market remains focused on the newly opened frontier of oral formulations, Lilly and Novo Nordisk have long since set their sights on moves in the far more distant corners of the strategic landscape.

At the core of Novo Nordisk's "post-semaglutide era" strategy is the fixed-dose combination CagriSema. It combines semaglutide with a long-acting amylin receptor agonist, cagrilintide.

Results from the Phase III REDEFINE 1 trial for CagriSema showed an average weight loss of 20.4%, which increased to 22.7% in the per-protocol population.

While CagriSema's weight loss data is impressive compared to semaglutide and tirzepatide, it did not meet Novo Nordisk's pre-specified efficacy target of 25%.

Adding to Novo Nordisk's concerns are recent developments from its rival. Lilly recently announced positive topline results from its Phase III TRIUMPH-4 trial for retatrutide, a GLP-1/GIP/GCG triple receptor agonist. In the trial, the 9mg dose group achieved an average weight loss of 26.4% (29.1 kg), while the 12mg dose group reached an astounding 28.7% (32.3 kg).

Some analysts have called these "the best weight loss results seen to date."

Although Novo Nordisk is not standing idle—having invested in two triple-target agonists of its own: UBT251 (a GLP-1/GIP/GCG agonist in-licensed from Livzon for up to $2 billion) and its internally developed GLP-1/GIP/Amylin triple agonist NN9662—its clinical progress in this critical next-generation arena currently lags behind that of Lilly's retatrutide.

Lilly, having just claimed the top spot, and Novo Nordisk, urgently seeking to counterattack, both face a common challenge in the new year: mounting pricing pressure.

In November 2025, Novo Nordisk and Lilly successively announced agreements with the U.S. government to lower the prices of their respective GLP-1 drugs.

Novo Nordisk committed to reducing the pricing of semaglutide starting in 2026 and expanding its accessibility under Medicare Part D, Medicaid, and for self-pay patients. Subsequently, Novo Nordisk further announced it would lower the cash price of semaglutide to $349 per month. Additionally, from now until the end of March 2026, U.S. patients can access a limited-time offer of $199 per dose.

The pricing for oral Wegovy is even more enticing. Its starting dose (1.5mg) has a cash price of $149 per month. Patients with commercial insurance may have out-of-pocket costs as low as $25 per month through savings programs.

Lilly announced that, starting April 1, 2026, Medicare beneficiaries will be able to access tirzepatide for an out-of-pocket cost of no more than $50 per month. Furthermore, the yet-to-be-launched orforglipron will also be included within the scope of this price reduction.

This drug pricing revolution, vigorously promoted by the Trump administration, has tangibly impacted market expectations for weight-loss drugs.

Asad Haider, Head of Global Healthcare Research at Goldman Sachs Research, forecasts that the market size for injectable GLP-1-based weight-loss drugs by 2030 is now projected to be approximately $95 billion, a downward revision of about 26.9% from the previous estimate of $130 billion. He noted this adjustment reflects evolving trends in drug pricing, patient treatment duration, and eligible patient populations.

The Goldman Sachs report highlights that pricing dynamics are the most significant factor affecting the U.S. market. Their analysis suggests that for every one-percentage-point change in the forecasted annual price erosion rate, the impact on peak U.S. sales could be as high as $6 billion.

This pricing uncertainty directly impacts corporate earnings forecasts. Lilly projects its 2026 sales to be in the range of $80 billion to $83 billion. The midpoint of this range represents a 25% growth over its 2025 sales of $65.2 billion. However, considering Lilly's revenue grew by 45% last year, the 2026 forecast appears relatively conservative.

Lilly's Chief Financial Officer, Lucas Montarce, stated during an earnings call that while the company remains optimistic about volume growth for its products, "price will likely be a drag on growth," with "part of that growth being offset by lower realized prices."

Mike Doustdar also acknowledged that 2026 will be a year of fierce competition for Novo Nordisk, particularly on the pricing front.

Compared to Lilly, Novo Nordisk faces an additional challenge: the impending patent cliff.

In 2026, the core compound patent for semaglutide is set to expire in several key international markets, including China. Once patent protection is lost, semaglutide will have to contend with price competition from generic versions.

Data from Insight Database shows that in the Chinese market, 10 generic versions of semaglutide have already filed for marketing approval, with another 11 in Phase III clinical trials. Novo Nordisk estimates that, at constant exchange rates, its 2026 sales and operating profit could decline by 5% to 13%.

The most captivating aspect of the weight-loss drug market lies in its unimaginably vast potential. This "Golden Sea," formed by the underlying demand from billions of obese and overweight individuals globally, is expansive enough to accommodate multiple giants sailing concurrently.

The World Obesity Atlas released by the World Obesity Federation indicates that in 2010 and 2015, the number of adults with overweight and obesity was 1.6 billion and 2.0 billion, respectively. Based on current trends, by 2030, overweight and obesity are projected to affect nearly 3 billion adults worldwide, accounting for approximately half of the global population aged 18 and above.

It is noteworthy that the latest research from Morgan Stanley points out that an estimated 1.3 billion overweight individuals globally currently meet the criteria for pharmacotherapy, yet only about 11% of them are using weight-loss medications. This signifies that the market's penetration rate remains in its early stages, with enormous white space yet to be filled.

Unlike the PD-1 market, which was ultimately dominated by a few winners, the depth and breadth of the weight-loss drug market provide ample room for numerous later entrants to survive and succeed. Therefore, while Eli Lilly and Novo Nordisk are locked in intense combat, a spectacular scene of "a thousand ships vying for position" is unfolding behind them.

Among all the pursuers, the most aggressive offensive undoubtedly comes from Pfizer.

Faced with repeated setbacks in its internally developed oral GLP-1 program, this "pharmaceutical giant" engaged in a blockbuster acquisition saga with Novo Nordisk in the second half of 2025. After a bidding war that drove the price up, Pfizer ultimately acquired the biotech company Metsera for $10 billion.

Following this massive acquisition, Pfizer's CEO, Albert Bourla, stated that a key task for the company this year is to "maximize the value of significant transactions."

Pfizer's execution speed has indeed been swift. On February 3rd, Pfizer announced positive topline results from the pivotal Phase IIb VESPER-3 trial for PF-3944 (formerly MET-097i). This is Metsera's flagship asset—a fully-biased, ultra-long-acting GLP-1 receptor agonist with a half-life of up to 380 hours, requiring only once-monthly injection.

The results showed that the low-dose (3.2mg/month) and mid-dose (4.8mg/month) groups achieved weight reductions of 10% and 12.3%, respectively, at week 28.

Investors were not satisfied with these results, as Pfizer's stock price fell by 3.34% on the day the data was released.

However, the verdict on whether this billion-dollar acquisition was worth it will depend on the final data readout for MET-097i. The pipeline acquired from Metsera includes more than just this candidate, such as another ultra-long-acting subcutaneous amylin analog, MET-233i, and other investigational oral formulations.

In this global weight-loss frenzy, other multinational corporations (MNCs) like Roche, AbbVie, and AstraZeneca have also entered the fray, ensuring no one misses this strategic race for the future.

The Chinese market, in particular, has become a fiercely contested battleground of its own.

Innovent Biologics' GLP-1R/GCGR dual agonist, mazdutide (IBI362), was approved in 2025, marking a milestone product in China's weight-loss and metabolic treatment field.

In 2025, Innovent's total product revenue surpassed the 10 billion RMB mark, reaching 11.9 billion RMB, a 45% year-over-year increase, with mazdutide being one of its strong growth engines. Zhongtai International forecasts that mazdutide's sales could reach 720 million RMB, 1.98 billion RMB, and 2.98 billion RMB in 2025, 2026, and 2027, respectively.

According to data from PharmaCube, as of April 2025, there were over 600 investigational pipelines in the global obesity treatment field. The United States and China are the primary markets, with approximately 200 assets in clinical stages in the U.S. and nearly 200 in clinical stages in China as well.

This fervent R&D landscape signals that this war is far from over. The coronation bells for the new king are precisely the bugle call for the next, even more intense battle. 2026 has just begun, and new fronts of the conflict are already fully deployed.