[Edaily Reporter Kim Seung-kwon ] As the first round of the “weight-loss drug war” between Eli Lilly and Novo Nordisk effectively tilts in Lilly’s favor, the two pharmaceutical giants have entered a high-stakes second round, competing over “how broadly they can address comorbidities simultaneously.”

Although a rivalry is once again taking shape in the “oral weight-loss drug” market, the focus of major institutional investors is not on the current sales gap but on the “gap in future pipelines.” This is because the paradigm of the weight-loss drug competition is shifting beyond simple cosmetic weight loss to the “multifunctional” realm of treating systemic metabolic disorders. PharmEdaily analyzed the future impact of these two companies’ pipelines.

Lilly Bets on Retatruotide, Which Offers “Results Comparable to Bariatric Surgery”

The recently announced second-quarter 2026 earnings season clearly illustrated the contrasting fortunes of the two companies in numerical terms. According to data filed with the U.S. Securities and Exchange Commission (SEC), Eli Lilly reported quarterly revenue of $22.9 billion, a 48% surge compared to the same period last year. This figure exceeded Wall Street expectations by a whopping $2.2 billion. In contrast, despite raising its full-year guidance, Novo Nordisk suffered a humiliating blow as its stock price plummeted more than 7% during trading after sales of its next-generation oral Wegovy fell short of market consensus. As of the 12th, Eli Lilly’s market capitalization stood at approximately 1,618 trillion won, while Novo Nordisk’s was about 223 trillion won, with the gap between the two companies continuing to widen.

Currently, Eli Lilly holds an overwhelming lead in the pipeline competition. Lilly’s next-generation obesity treatment candidate, “Retatrutide,” has been producing remarkable clinical data day after day in the first half of this year. This compound is the first “triple-action agent” in its class, combining the effects of existing GLP-1 (glucagon-like peptide-1) and GIP (gastric inhibitory polypeptide) with glucagon receptor activity. It is essentially an evolved version of Mounjaro and Zepbound (active ingredient: tirzepatide), which are currently taking the market by storm.

The results of the pivotal “TRIUMPH-1” clinical trial surprised the medical community. In this 80-week trial involving obese adults, the group receiving the highest dose of 12 mg lost an average of 31.9 kg—or 28.3% of their body weight. Notably, 65.3% of this group entered the normal weight range (body mass index [BMI] below 30), and 45.3% lost more than 30% of their body weight. These are unprecedented figures that were previously only expected from surgical “bariatric and metabolic procedures” such as gastric bypass surgery.

Subsequent “TRIUMPH-2” and “TRIUMPH-3” clinical trials also confirmed weight loss of up to 22.6% in obese patients with type 2 diabetes and cardiovascular disease. Blood triglycerides were reduced by 37%, and high-sensitivity C-reactive protein (hsCRP), a marker of systemic inflammation, was reduced by as much as 51.2%.

Dr. Dan Skovronsky, Chief Scientific Officer (CSO) at Eli Lilly, stated during the second-quarter conference call, “The clinical data demonstrated by Retatruotide are rewriting the history of obesity treatment,” and “By going beyond simple weight loss to dramatically improve patients’ inflammatory markers and lipid metabolism, it is proving that it can alter the fundamental course of metabolic diseases,” he said with confidence. However, the failure to clearly demonstrate a significant reduction in cardiovascular events remains a minor drawback; nevertheless, given the exceptional strength of the overall Phase 3 clinical trial package comprising five studies, the company is expected to have no difficulty filing for U.S. FDA approval in the first quarter of 2027.

A J.P. Morgan analyst covering the biohealthcare sector noted, “Lilly has already secured a powerful cash cow with Zepbound, and with Retatruotide—a potential alternative to bariatric surgery—and the oral drug Foundayo (oroglifron) now in its arsenal, it has effectively completed a ‘seamless portfolio.’” "It will be difficult to find a competitor capable of challenging Lilly’s dominance for the foreseeable future," the analyst added.

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Painful Blow for Novo Nordisk… Platform Expansion Stalls Following ‘Technical Defeat’ for Cagrisema

In contrast, the outlook for the next-generation pipeline of Novo Nordisk—the “pioneer of obesity drugs”—is bleak. This is because “CagriSema,” which was touted as the key successor to Wegovy (semaglutide), has suffered a series of painful setbacks.

CagriSema is a combination drug that combines 2.4 mg of semaglutide with 2.4 mg of the amylin analog cagrilinotide. However, in the pivotal 84-week “REDEFINE 4” clinical trial, which featured a head-to-head comparison with Lilly’s tirzepatide 15 mg, it failed miserably to demonstrate “non-inferiority,” its primary endpoint. According to the clinical results, the weight loss rate in the Cagrisema group was 23.0%, falling short of that of tirzepatide (25.5%); in an analysis reflecting real-world treatment conditions, the gap widened further (20.2% vs. 23.6%). The drug failed to meet even the clinical threshold of demonstrating at least “similar efficacy” compared to the competitive drug. On the day this news broke, Novo Nordisk’s stock price plummeted by more than 16%.

Martin Holst Lange, Senior Vice President of R&D at Novo Nordisk, stated during a conference call, “While we are disappointed that we did not meet the primary endpoint in the REDEFINE 4 study, this does not mean the platform has failed,” and “We will continue to evaluate its potential through the ongoing REDEFINE 11 clinical trial and additional studies on high-dose cagrisema,” he added in an attempt to downplay the situation.

However, this failed to reverse the market’s lukewarm reaction. To make matters worse, “Monlunabant,” a candidate drug for treating cardiovascular disease, also ran aground in late-stage clinical trials, forcing the company to record an impairment loss of over 900 billion won on its second-quarter financial statements.

The Next Battleground Is “Comorbidities”… Targeting Sleep Apnea, Brain Disorders, and Addiction

Industry analysts believe that future dominance in the weight-loss drug market hinges on how successfully GLP-1 agonists can expand their indications to a wide range of conditions. One-dimensional competition focused solely on weight loss metrics has already lost its ability to differentiate products, and the market is now looking five years ahead—a factor that is influencing stock prices.

The most pressing issue for both companies right now is securing justification for coverage under private and public insurance plans. Lilly recently added moderate-to-severe obstructive sleep apnea as an indication for Zepbound. By targeting this market—which alone has 30 million patients in the U.S.—the company has gained a powerful weapon to pressure insurers that have previously denied coverage by labeling the treatment as merely “cosmetic.” Novo Nordisk has also lowered insurance barriers by demonstrating the cardiovascular disease prevention benefits of Wegovy through its large-scale cardiovascular clinical trial (SELECT).

Furthermore, both companies are setting their sights on the markets for central nervous system (CNS) disorders and addiction treatment. Although Novo Nordisk failed to demonstrate disease suppression in the Phase 3 “EVOKE” trial for Alzheimer’s disease patients, it remains hopeful following recent large-scale real-world data (RWD) reporting contrasting results: GLP-1 users had a roughly 54% lower risk of developing dementia.

In particular, the treatment of “alcohol and drug addiction” is considered a new blue ocean market on par with the obesity market. A flood of research is emerging showing that GLP-1 drugs act on the brain’s reward circuitry to regulate dopamine secretion and reduce inflammatory responses, thereby alleviating symptoms of addiction. It is widely believed that Lilly’s surprise acquisition last July of “Ativekli,” a mental health drug developer valued at $3.8 billion, using its massive cash reserves to secure a leading position in the market for depression and addiction treatments, is closely tied to this trend.

Morgan Stanley’s senior healthcare analyst in the U.S. stated in a recent report, “As confirmed at the American Diabetes Association (ADA) 2026 conference, with the number of latecomers growing exponentially, weight loss of only 15–20% is no longer enough to capture the market’s attention,” adding "The next battleground in the obesity 'big match' is the 'breadth of clinical value,' encompassing patients’ hearts, livers, brains, and mental health. As things stand, Eli Lilly—which is leading the way with preemptive M&A and extensive pipeline trials—is two steps ahead of Novo Nordisk in preparing for the future," the analyst concluded.