Novo and Lilly race to bring next-generation GLP-1s to market

Novo Nordisk and Eli Lilly are working to bring the next generation of GLP-1s to market.

The two pharma giants have already made billions from their blockbuster diabetes drugs Ozempic and Mounjaro as well as their weight loss counterparts Wegovy and Zepbound. Now, they’re looking to create more effective versions of these medications that could also treat a range of other conditions such as heart and kidney disease.

The two GLP-1s experts say may receive FDA approval next are Novo’s CagriSema and Lilly’s retatrutide. The medications are being tested as treatments for both obesity and diabetes, but Novo asked the FDA in December to approve CagriSema as an obesity treatment first.

Lilly did not respond to a request for comment on which indication they plan to submit retatrutide for first, but Daniel Skovronsky, Lilly’s chief scientific and product officer and president of Lilly Research Laboratories, said during the company’s August 5 earnings call that with the completion of two recent clinical trials, “we now have the clinical data package to support global registrations in obesity, obstructive sleep apnea, and knee osteoarthritis pain.”

The market for obesity treatments is significantly larger than that for Type 2 diabetes. An estimated 1 billion people worldwide have obesity, according to the World Health Organization, while an estimated 589 million people worldwide have diabetes, with more than 90% of that population living with Type 2, according to the International Diabetes Foundation.

The R&D efforts highlight “how Lilly and Novo are not just sitting still and hoping for the best,” Evan Seigerman, managing director and head of healthcare research at BMO Capital Markets, told Healthcare Brew.

A closer look. Novo’s CagriSema is a once-weekly injection made from a combination of semaglutide (the active ingredient in Ozempic), and cagrilintide, a long-acting amilyn analog. Amilyn, a hormone the pancreas releases after eating, plays a role in regulating appetite, managing blood sugar, and supporting bone health.

Semaglutide and the amilyn analog are thought to have potentially complementary effects that may enhance weight loss potential and improve blood sugar control, according to Jason Brett, principal medical head at Novo Nordisk.

However, clinical trial results released in February found that CagriSema was not as effective as Lilly’s Zepbound when it came to weight loss. In response, Novo’s stock fell more than 16%. The same month, trial results showed that CagriSema was more effective than semaglutide alone for weight loss in people with diabetes.

Novo filed for FDA approval of CagriSema as an obesity treatment in December 2025 and expects a decision in Q4 2026, Brett told us.

Lilly’s retatrutide, on the other hand, is a triple agonist, which means it activates receptors for three hormones: GLP-1, GIP, and glucagon.

GLP-1 is a hormone that triggers insulin release and helps people feel full. GIP stands for glucose-dependent insulinotropic polypeptide, a hormone released by the small intestine to help regulate blood glucose and stimulate insulin secretion. And glucagon is a hormone that prevents blood sugar from falling too low.

Lilly’s Zepbound is a double agonist containing both GLP-1 and GIP. The theory with retatrutide is that adding in glucagon can then enhance weight loss potential, Seigerman said.

Retatrutide is in Phase 3 clinical trials, and preliminary results have shown it can help patients on the highest dose lose an average of 28.3% of their body weight over 80 weeks. A study comparing how retatrutide and Zepbound stack up against each other is expected to wrap up in December.

During the recent earnings call, Skovronsky said the company plans to submit retatrutide for FDA approval in the first quarter of 2027. It’s not clear how soon the FDA would make a decision after that.

Lilly plans to classify retatrutide as a biologic drug in its application. Biologics are medicines derived from living organisms, such as proteins. That would make it harder for compounders to make copycat versions of the medicine, as biologics are not legally allowed to be compounded.

Lilly has already filed lawsuits against six companies making compounded versions of retatrutide, despite the drug not even being FDA approved yet.

However, there’s been disagreement between Lilly and the FDA on whether retatrutide meets the definition of a biologic.

Winning over insurers’ hearts. Whatever the next class of weight loss and diabetes treatments turns out to be, the medicines will have to win over insurers if drugmakers want them on formularies.

Mitzi Wasik, SVP of practice strategy and innovation at the professional association the Academy of Managed Care Pharmacy, told Healthcare Brew that, when deciding whether or not to cover any GLP-1 products that hit the market, payers will likely look at which are most likely to improve healthcare costs.

For instance, a medicine that’s most effective at controlling diabetes would also be more effective in reducing diabetes-related comorbidities like hypertension, which would then lower overall healthcare costs in the long term, Wasik said.

Ultimately, having more weight loss treatment options is a good thing, Wasik said, as that could help drive down the costs of the medicines already on the market.

Arms race. Novo and Lilly have been in a race to establish dominance in the metabolic health market for years, each leading at different points.

When it comes to who has the advantage at the moment, Seigerman said it’s somewhat split. On the one hand, retatrutide looks like it may be the most effective option for weight loss, which gives Lilly a competitive edge.

However, Novo’s Wegovy pill has outperformed Lilly’s Foundayo pill when it comes to prescription volume. The Wegovy pill launched in January, while Foundayo launched in April. The Wegovy pill saw 137,000 prescriptions during week 18 after launch, while Foundayo had just under 39,000 at the same point, according to Iqvia data reported by Fierce Pharma.

Because of the Wegovy pill’s performance, “Novo is definitely holding its own and will continue to do so,” Seigerman said.

For other companies to be able to compete with Lilly and Novo in the metabolic health market, they’ll have to bring a product that’s differentiated either by efficacy, convenience, or tolerability, according to Seigerman. For instance, some drug companies, like Pfizer, have been testing once-a-month injections as an improvement over existing GLP-1 medicines that require weekly shots.

“You have to have somebody who brings innovation to the market versus just a ‘me too,’” Seigerman said.