From June 5 to 8, the American Diabetes Association (ADA) Annual Meeting took place in New Orleans. This is the world's largest and most prestigious academic conference in the field of diabetes.

 

Five years ago, Novo Nordisk publicly presented core Phase III clinical data from its STEP series at this conference, officially kicking off the weight-loss drug boom. Four years ago, Eli Lilly publicly presented Phase III data for tirzepatide from SURMOUNT-1, sounding the charge for its counter-offensive.

 

Over the past year, the weight-loss drug market has been completely transformed. Tirzepatide, with its overwhelming sales data, has successfully overtaken semaglutide to become the world's best-selling drug. Novo Nordisk is fighting back with oral Wegovy, which currently holds a commanding lead in prescription volume over Eli Lilly's oral small-molecule drug Foundayo.

 

Beyond the seemingly entrenched duopoly, the race for the "third place" has also intensified – Pfizer and Roche are making heavy bets, while Chinese forces such as Innovent Biologics and Hengrui Medicine are taking turns on the stage, announcing their presence to the world with blockbuster data.

 

One question grows increasingly intriguing: who will become the true "third pole" in this race of the century?

 

 

TONACEA 01: The Duopoly War Escalates

 

The battle between injectable tirzepatide and semaglutide has already seen a winner.

 

In the first quarter of 2026, tirzepatide contributed US$12.822 billion in revenue to Eli Lilly, while semaglutide's global sales for the same period were approximately DKK 52.888 billion (approximately US$8.277 billion). The gap between them has widened further.

 

But on the other side, the oral battle is just igniting.

 

In December 2025, Novo Nordisk's oral Wegovy received FDA approval, becoming the world's first oral GLP-1 receptor agonist for weight management, firing the first shot in its counter-offensive.

 

Eli Lilly followed closely, securing FDA approval for its oral small-molecule GLP-1 receptor agonist orforglipron (brand name Foundayo) in April of this year for the treatment of obesity or overweight adults with weight-related comorbidities.

 

However, this time, the script of tirzepatide's "latecomer overtaking" did not replay itself. Looking at real-world prescription data, the oral formulation of Wegovy, leveraging Novo Nordisk's years of accumulated brand recognition and physician prescribing habits, continues to lead.

 

According to Fierce Pharma, over five months of sales, Wegovy has accumulated 3 million prescriptions. Around eight weeks after launch, Wegovy had approximately 73,000 prescriptions; after 12 weeks, it surpassed 1 million prescriptions. Eli Lilly's Foundayo, since its launch, has accumulated only about 20,000 prescriptions.

 

This stark gap reflects both the user base that oral semaglutide has inherited from its injectable formulation and the challenges Eli Lilly faces in promoting its oral formulation.

 

To turn the tide, Eli Lilly publicly presented data from the Phase III ACHIEVE-3 "head-to-head" study comparing Foundayo to oral Wegovy at this ADA meeting.

 

The results showed that over 52 weeks of treatment, the highest dose (17.2 mg) of Foundayo achieved a 2.2% reduction in HbA1c from baseline, compared to a 1.4% reduction with oral Wegovy (14 mg), a 57.1% greater reduction. On weight loss, Foundayo achieved a 9.2% (19.7 lb) reduction, while Wegovy achieved 5.3% (11.0 lb), a 73.6% greater relative weight loss. On HbA1c target attainment (<7%), the rates were 85.4% and 66.1%, respectively; the proportions achieving normoglycemia (<5.7%) were 37.1% vs 12.5%. It can be said that Foundayo achieved comprehensive superiority in efficacy.

 

The disappointing aspect was tolerability. The discontinuation rate due to adverse events in the highest-dose Foundayo group reached 9.7%, compared to only 4.9% in the highest-dose Wegovy group. Considering that the compared doses were not fully equivalent (17.2 mg vs 14 mg), and the obvious tolerability shortcomings, this data lacks the "overwhelming" narrative power of tirzepatide's "head-to-head" victory over semaglutide.

 

However, Eli Lilly's true "trump card" lies in the subsequent release of Phase III data for retatrutide, its GIP/GLP-1/GCG triple receptor agonist. The ADA featured results from two core studies – TRIUMPH-1 (obese population) and TRANSCEND-T2D-1 (type 2 diabetes population).

 

TRIUMPH-1 results showed that retatrutide met primary endpoints in every trial, significantly reducing body weight and significantly improving knee osteoarthritis pain and obstructive sleep apnea.

 

At 80 weeks, participants in the 9 mg and 12 mg dose groups achieved average weight loss of 64.4 lb (25.9%) and 70.3 lb (28.3%), respectively. The 4 mg group also achieved 19% weight loss.

 

Facing Lilly's multi-target assault, Novo Nordisk responded with data from three Phase III studies (REIMAGINE 1-3) of its combination therapy CagriSema (semaglutide + long-acting amylin analog cagrilintide).

 

In the REIMAGINE 1 trial, in patients with inadequate diet and exercise control, the CagriSema 2.4 mg group achieved an average weight loss of 13.8% after 40 weeks of treatment, while the 1 mg group achieved 11.8%. In patients inadequately controlled on metformin ± SGLT2 inhibitors and on basal insulin, CagriSema similarly showed dual benefits of glycemic control and weight loss. Gastrointestinal adverse events were most common across the three trials, with overall tolerability being manageable.

 

Thus, the duopoly's competition has escalated from single-molecule drugs to an all-out war covering multi-targets, combination therapies, oral formulations, and injectables.

 

TONACEA 02: Who Is the Third Place?

 

Eli Lilly and Novo Nordisk have built a duopoly that is currently difficult to shake, leveraging their first-mover advantages, vast clinical data, and mature commercial systems. But for all the chasers, the suspense is not "whether they can overturn the duopoly," but "who can become the recognized third place."

 

This position not only implies hundreds of billions of dollars in market capitalization potential, but also represents having a true strategic position in the metabolic field. Looking at the signals released from this ADA, the path choices of several MNCs have highly diverged, presenting distinct "asymmetric competition" characteristics.

 

Among all these potential competitors, Pfizer may not be the closest to the "third place" position, but it is certainly the one willing to spend the most.

 

In 2025, Pfizer spent US$10 billion to "snatch" Metsera away from Novo Nordisk, gaining the ultra-long-acting GLP-1 receptor agonist berobenatide through this transaction.

 

At ADA, Pfizer publicly presented data from the VESPER series of Phase IIb studies of berobenatide. In the 32-week exploratory extension part of the VESPER-1 study, subjects receiving once-weekly 2.4 mg berobenatide for 32 weeks achieved a mean body weight reduction of 15.9% without placebo adjustment, with no plateau observed.

 

More critically, the drug was well tolerated, with low rates of gastrointestinal adverse events and discontinuation even with a rapid dose-escalation schedule. Based on these results, Pfizer plans to initiate 10 Phase III clinical trials of berobenatide in 2026 for chronic weight management and obesity-related comorbidities. Pfizer's bet is clear and aggressive: use the convenience of a monthly formulation to carve out a foothold from Eli Lilly and Novo Nordisk.

 

Roche has built a dual-asset matrix – the long-acting amylin analog petrelintide and the GLP-1/GIP dual receptor agonist enicepatide.

 

Petrelintide's mechanism of action is completely different from GLP-1. Its core selling point is not extreme weight loss numbers, but excellent tolerability. The Phase II ZUPREME-1 study showed that over 42 weeks of treatment, petrelintide led to an average body weight decrease of 10.7%, but only 1.5% of participants discontinued due to gastrointestinal adverse events, with vomiting rates even lower than the placebo group.

 

For patients who cannot tolerate the side effects of GLP-1 drugs, petrelintide offers a highly attractive alternative. Enicepatide, on the other hand, is responsible for "showing off its muscles." Its Phase II data showed that the highest dose group achieved an average body weight decrease of 22.7% after 48 weeks of treatment, with more than a quarter of subjects achieving weight loss exceeding 30%.

 

AstraZeneca's path is more unique. The weight loss data for its oral small-molecule GLP-1 drug elecoglipron (11.8% at 36 weeks) is not particularly outstanding. But AstraZeneca's unusual thinking is to seek a combination strategy of elecoglipron and dapagliflozin. The core strategy is to embed the weight-loss drug into its existing cardiorenal metabolic product matrix, achieving the combined benefit of "glucose lowering + weight loss + cardiorenal protection."

 

Regeneron is trying to solve the muscle loss problem associated with current GLP-1 drugs during weight loss.

 

Regeneron had previously released complete data from the Phase II COURAGE trial. The study showed that combining semaglutide with muscle-sparing trevogrumab (GDF8 antibody) and garetosmab (anti-activin A) prevented approximately 50% of semaglutide-induced muscle loss, offering obvious advantages in fat reduction and muscle gain. If this combination strategy succeeds, Regeneron will have a completely differentiated story.

 

In summary, the path differences among these MNCs are now very clear. The competition for "third place" is no longer about who can achieve weight loss numbers closer to Eli Lilly or Novo Nordisk, but who can find a strategic window of their own within the duopoly's walls and dig a moat deep enough.

 

TONACEA 03: The Chinese Contingent Arrives

 

Looking at the global competitive landscape of weight-loss drugs, the strength of the "Chinese contingent" is increasingly difficult to ignore. At this ADA, over 20 Chinese companies and more than 50 studies were selected – the largest gathering of Chinese pharmaceutical companies at this conference in history.

 

Innovent Biologics' focus is highly concentrated on the GCG/GLP-1 dual receptor agonist mazdutide. This is the world's only approved drug targeting this target, and it has now achieved dual approval in China for both weight loss and blood sugar reduction indications.

 

At this ADA, Innovent brought three oral presentations covering different populations.

 

Among them, data from the Phase III GLORY-2 study targeting Chinese patients with moderate-to-severe obesity (BMI ≥30 kg/m²) showed: average weight loss of 18.55% (placebo group 3.02%) at 60 weeks, with 44.0% of subjects achieving ≥20% weight loss; in the subgroup without type 2 diabetes, average weight loss reached 20.08%; liver fat content decreased by an average of 71.9% from baseline (placebo group increased by 5.1%); discontinuation rate due to adverse events was only 2.9%.

 

These data indicate that mazdutide has solid efficacy and safety in the moderate-to-severe obese population, and the liver fat-clearing effect of its GCG target is worth further exploration.

 

Hengrui Medicine demonstrated even greater ambition. At this ADA, Hengrui publicly presented three studies of its self-developed GLP-1/GIP dual receptor agonist retatrutide (HRS9531).

 

Among them, a Chinese Phase II weight loss study of oral retatrutide tablets showed: after 26 weeks of treatment, the 10 mg, 25 mg, and 50 mg groups achieved weight loss from baseline of 6.9%, 12.1%, and 12.1%, respectively, all significantly superior to the placebo group (2.3%, p values 0.0027, <0.0001, <0.0001). The weight loss trend in the 50 mg group was steeper than in the 25 mg group from week 8 onwards, with no plateau observed through 26 weeks. The incidence of gastrointestinal adverse events was low (vomiting rate 11.4% in the 25 mg group, 7.5% in the 50 mg group).

 

If all goes well, Hengrui Medicine is about to bring a dual-target weight-loss drug into the oral era. Currently, the marketing application for retatrutide injection has been accepted by the NMPA, with global Phase III clinical trials being advanced by partner Kailera Therapeutics; Phase III trials of the oral tablet are also progressing simultaneously in China.

Additionally, there was an intriguing "off-stage episode" at this ADA.

 

Twenty-week interim analysis data from the head-to-head Phase II SLIMMER-UP-SWITCH study of Pfizer's cAMP-biased GLP-1 receptor agonist ecnoglutide versus semaglutide showed that ecnoglutide achieved an average body weight decrease of 12.8% at 20 weeks, significantly superior to semaglutide's 9.5% (P<0.0001), a 35% greater decrease; the proportion of patients achieving ≥10% weight loss reached 74%, nearly double the 40% in the semaglutide group; waist circumference reduction was also increased by 20%.

 

After the data were released, Novo Nordisk quickly responded, pointing out that the study was a Phase II, open-label, interim analysis with a sample size of only 163 patients, and the results still need verification from larger sample and longer-term studies. Novo Nordisk cited the STEP series studies, noting that the weight loss magnitude of semaglutide at 20 weeks varies across different studies.

 

The drug that gave Novo Nordisk a sense of "crisis" actually originates from the Chinese company Sciwind Biosciences. In February 2026, Sciwind entered into a commercial strategic collaboration with Pfizer, granting Pfizer exclusive commercial rights to the product in mainland China, with Sciwind eligible for up to US$495 million in total payments. Ecnoglutide was approved in China for adult type 2 diabetes in January 2026, and its marketing application for long-term weight management has also been accepted by the NMPA.

 

This exchange across the air reflects the growing importance and wariness that global giants are placing on local Chinese innovation data. Regardless of the final outcome, one fact is undeniable: Chinese pharmaceutical companies now have the strength to engage in head-to-head challenges on top-tier stages like ADA – and to make Novo Nordisk nervous.

 

Final Thoughts

 

Over the past few years, the ADA has witnessed the weight-loss track evolve from a "two-horse race" to a "hundred flowers blooming." This year, we saw some betting on monthly or oral formulations to improve adherence, others pursuing better tolerability, and still others trying combination therapies to solve the pain point of muscle loss. Each new molecule is trying to answer a different question.

 

This reveals a deeper logic: when weight loss efficacy approaches its ceiling, true differentiation has long come from things beyond the weight loss number. The next key to victory in weight-loss drugs is not who can make the next "tirzepatide" or "semaglutide," but who can solve the things that tirzepatide and semaglutide cannot do.

 

References:

• Company announcements

• The Oral GLP-1 Tracker; Fierce Pharma

• Semaglutide embroiled in weight loss data dispute with domestic GLP-1 drugs! Industry insiders: future focus on multi-target and indication expansion; National Business Daily