The Obesity Drug Race: Who Can Challenge Lilly and Novo?
Obesity has become one of the biggest opportunities in drug development. By 2035, an estimated 1.53 billion adults globally are projected to be living with obesity. When overweight is included, the number could reach 3.3 billion, or more than half of the world’s adult population. The economic impact could exceed $4 trillion annually.
The pharmaceutical market has responded at extraordinary speed. The global obesity medicines market reached $66 billion in list-price sales in 2025 and is forecast to reach approximately $92 billion in 2026.
Eli Lilly and Novo Nordisk have so far defined this market. Semaglutide and tirzepatide transformed expectations for pharmacological weight management and established a new benchmark for obesity treatment.
However, their dominance is unlikely to go unchallenged. A growing group of pharma and biotech companies is advancing oral therapies, next-generation incretins, amylin-based drugs and other novel approaches, while major acquisitions and licensing deals are rapidly reshaping the competitive landscape.
The question is no longer whether competition is coming, but who has the strongest chance of challenging Lilly and Novo, and what it will take to succeed in the next phase of the obesity drug race.
Lilly and Novo keep raising the efficacy bar
Semaglutide established that pharmacological treatment could deliver average weight loss approaching 15% in people with obesity. Tirzepatide subsequently pushed results beyond 20% in people without diabetes.
Now the bar is moving again. Lilly’s investigational triple agonist retatrutide, which targets GIP, GLP-1 and glucagon receptors, reported mean weight loss of 28.3% at 80 weeks at the highest dose in the Phase III TRIUMPH-1 study. Among participants with a baseline BMI of at least 35 who continued into the extension, mean weight loss reached 30.3% at 104 weeks. Nearly half of participants receiving the 12 mg dose in TRIUMPH-1 lost at least 30% of their body weight.
Competitors are also approaching the 20% threshold. Roche’s dual GLP-1/GIP agonist enicepatide, formerly CT-388, produced 22.5% placebo-adjusted weight loss at 48 weeks at the highest dose in Phase II, without reaching a weight-loss plateau.
These results create a much harder environment for new entrants. A drug producing 15% weight loss would have looked transformational several years ago. Today, a sponsor developing a therapy in that range increasingly needs another reason for patients and physicians to choose it.
That raises a different question: If efficacy alone is no longer enough, where will the next generation of obesity drugs compete?
The next race is about more than weight loss
Tolerability could matter as much as another percentage point. The remarkable efficacy of incretin therapies comes with a familiar challenge: gastrointestinal adverse events.
Nausea, vomiting and other GI effects can complicate dose escalation and contribute to treatment discontinuation. In a chronic condition in which therapy may continue for years, persistence matters. This is one reason amylin has become one of the most closely watched areas of obesity development.
Petrelintide, being developed by Zealand Pharma in partnership with Roche, produced up to 10.7% mean weight loss at 42 weeks in the Phase II ZUPREME-1 study versus 1.7% with placebo. But the potentially more important signal was tolerability. At the maximally effective dose, no vomiting was reported and there were no discontinuations due to gastrointestinal adverse events.
That creates a different competitive proposition. The future question may not always be whether Drug A produces 22% weight loss while Drug B produces 20%. It may be whether patients are more likely to stay on Drug B.
For chronic obesity management, real-world persistence may ultimately matter almost as much as maximum efficacy.
Convenience is becoming another battleground
Weekly injections transformed obesity treatment. They may not remain the only dominant model.
More than 40% of clinical-stage obesity drugs in development were oral formulations, highlighting how aggressively the industry is pursuing alternatives to injectable therapy.
Several strategies are now converging.
- Novo Nordisk’s oral semaglutide was approved by the FDA for obesity as Foundayo on April 1, 2026, bringing an oral GLP-1 option into obesity treatment.
- Lilly is advancing orforglipron, an oral small-molecule GLP-1 receptor agonist.
- AstraZeneca’s oral elecoglipron produced 8% weight loss at 36 weeks in the Phase IIb VISTA study and has moved into Phase III development.
Other companies are taking the opposite approach: instead of eliminating injections, they are trying to make them dramatically less frequent.
- Amgen is testing maridebart cafraglutide with extended dosing intervals, including every eight weeks and quarterly administration in maintenance settings.
- Pfizer is developing berobenatide with the potential for monthly maintenance dosing.
The implications could be significant. If obesity requires long-term treatment, reducing dosing from 52 injections per year to 12, six or even four could meaningfully change the patient experience.
The next breakthrough may therefore come not from another large increase in efficacy, but from making effective obesity treatment substantially easier to live with.
Beyond weight loss: obesity is becoming a more differentiated market
New mechanisms and broader therapeutic indications are creating additional ways for obesity drugs to differentiate. The obesity market is beginning to expand beyond the traditional GLP-1 and GIP model. While GLP-1 and GIP-based therapies accounted for approximately 96% of the obesity drug market in 2024, their share of the overall market is projected to decline to 72% by 2034 as new approaches, including amylin-based therapies and muscle-preserving strategies, gain ground.
At the same time, obesity drugs are increasingly being developed not only for weight loss, but also for obesity-related conditions such as cardiovascular disease, MASH, sleep apnea and osteoarthritis. This creates new opportunities for differentiation. A therapy may not need to produce the greatest overall weight loss if it can preserve lean mass or deliver particularly strong benefits in a specific patient population.
This shift also changes how obesity trials are designed and executed. More targeted indications mean sponsors need access to the right patients, specialists, referral networks and diagnostic capabilities. In markets where GLP-1 use is already widespread, finding treatment-naïve patients may become increasingly difficult.
The obesity market is therefore evolving from one broad race for greater weight loss into multiple races to deliver the right treatment for the right patient.
Who can challenge Lilly and Novo?
The commercial opportunity for challengers is substantial. Novo Nordisk and Eli Lilly currently dominate obesity drug sales, but competition is intensifying as new oral therapies, next-generation incretins, amylin-based drugs and other differentiated approaches enter the market.
The race is already accelerating. Pfizer’s acquisition of Metsera, potentially worth around $10 billion including contingent payments, and a growing number of licensing deals show how aggressively companies are building obesity pipelines.
So, who is best positioned to challenge Lilly and Novo? Here are 10 companies to watch, based on pipeline maturity, efficacy potential, differentiation and portfolio depth.
Rank | Company | Why it matters |
1 | Eli Lilly | Zepbound gives Lilly the current benchmark, while orforglipron and retatrutide could provide successive generations of growth. |
2 | Novo Nordisk | Wegovy established the modern obesity franchise, while oral semaglutide, higher-dose Wegovy, CagriSema and next-generation programs give Novo considerable pipeline depth. |
3 | Roche | Enicepatide brings strong efficacy, while petrelintide adds a differentiated amylin and tolerability strategy. |
4 | Pfizer | The Metsera acquisition transformed Pfizer’s obesity position, adding long-acting incretin and amylin programs. |
5 | Amgen | Maridebart cafraglutide offers one of the clearest convenience strategies if extended maintenance dosing proves successful. |
6 | AstraZeneca | Oral elecoglipron, a growing pipeline and external partnerships provide multiple routes into obesity and cardiometabolic disease. |
7 | Boehringer Ingelheim | Survodutide is one of the more advanced challenger programs, with potential differentiation through glucagon biology and metabolic comorbidities. |
8 | Regeneron | Its muscle-preservation strategy addresses not simply how much weight patients lose, but what kind of weight they lose. |
9 | Viking Therapeutics | VK2735 gives Viking a differentiated dual GLP-1/GIP program, with both injectable and oral formulations in development and a potentially competitive efficacy profile. |
10 | Kailera Therapeutics | Ribupatide provides a credible late-stage efficacy story, although global development and commercial scale remain to be proven. |
Turning obesity innovation into successful trials
The opportunity in obesity remains enormous, but the threshold for differentiation is rising. The next generation of therapies will need to demonstrate not simply that they can reduce body weight, but that they offer something meaningfully better, whether through efficacy, tolerability, convenience, body composition or benefits in specific comorbidities.
Proving that difference will also require increasingly sophisticated clinical development strategies. As more programs enter late-stage development, patient identification, site selection, prior GLP-1 exposure, retention and geographic strategy will become increasingly important.
At Cromos Pharma, we work with sponsors to translate promising science into clinical trials that can be executed in the real world, from feasibility and site selection to patient recruitment and study delivery.
If you are planning an obesity or metabolic clinical trial, contact our team at inquiry@cromospharma.com to discuss how we can support your development program.
