Even as industry watchers pit the two obesity assets against one another, it’s too early to say whose next-generation incretin stands supreme between Novo Nordisk’s CagriSema and Eli Lilly’s retatrutide, Novo’s chief scientific officer has suggested to Fierce.
Novo is positioning CagriSema—which combines the amylin analog cagrilintide with the company’s well-known GLP-1 quantity semaglutide—as the heir apparent to its Ozempic and Wegovy empires. Cagrisema has so far been tied to 23% weight loss after 84 weeks of treatment in a phase 3 obesity trial. At the American Diabetes Association 2026 Scientific Sessions in New Orleans last weekend, Novo also gave special attention to the asset’s potential to help diabetes patients across a range of disease stages.
Nevertheless, early comparisons between CagriSema and Lilly’s own next-gen metabolic darling, the triple agonist retatrutide, have typically seen the Danish pharma on the backfoot.
In fact, analysts at RBC Capital Markets were quick to christen Lilly the “clear winner from ADA” after the meeting wrapped up this week, giving special mention to retatrutide and the weight loss of 28% at 80 weeks and 30% at 104 weeks shown at its highest dose in patients with obesity.
While retatrutide demonstrated “some really impressive weight loss” data at the conference, Novo CSO Martin Holst Lange, M.D., Ph.D., told Fierce that the company believes it has “four assets in our clinical pipeline that look to be competitive with that.”
“I think at some point it’s not about the weight loss anymore,” Lange said in an interview on the sidelines of the conference. While multiple companies are now developing obesity assets of their own that look to “give ranges of weight loss,” other factors like tolerability and a drug’s capability to tackle comorbidities will become increasingly important as the field continues to expand, he argued.
The question, he reckoned, is: “How do you live not only a thinner life, but also a better life?”
While the 23% average weight loss CagriSema has demonstrated in pivotal studies in obesity is “substantial,” Lange said he “had to admit it’s not competitive to what we saw from retatrutide” at ADA.
That said, Novo is running another late-stage trial known as Redefine 11, which the company last year noted was designed (PDF) to “[e]xplore further weight loss potential” for CagriSema through measures like dose re-escalation and longer trial durations.
During the interview, Lange reiterated that Novo expects to see “even higher weight loss” from that study, adding that the “jury is still out” on how the two assets ultimately compare.
In CagriSema’s other core indication target, Type 2 diabetes, the combination asset has, conversely, “shown really good glycemic control—actually better than what we saw yesterday from our competitors,” Lange pointed out to Fierce.
The CagriSema weight loss stats in diabetes patients, who have more difficulty losing weight due to metabolic factors, are “in the ballpark of what they’ve also seen,” Lange said of Novo’s and Lilly’s rival candidates.
Using the efficacy estimand in Novo’s 68-week Reimagine 2 trial, the highest 2.4-mg/2.4-mg dose of CagriSema was linked to a 1.91% reduction in HbA1c from a baseline of 8.2%, as compared to a roughly 0.1% drop among the placebo cohort and 1.75% reduction on the highest approved diabetes dose of Novo’s own Ozempic. Average weight loss on the highest CagriSema dose worked out to a 14.2% reduction, versus a 1.5% reduction on placebo and a 10.2% reduction for patients taking semaglutide 2.4 mg.
Though cross-trial comparisons are inherently flawed, Lilly has previously tied retatrutide to average reductions in A1C of 1.7%, 1.9% and 1.9% on the 4-mg, 9-mg and 12-mg doses, respectively, after 40 weeks of treatment and when accounting for all patients in its study.
Meanwhile, following closely behind CagriSema is Novo’s zenagamtide, a unimolecular peptide agonist of the GLP-1 and amylin receptors, which has been linked to 24% weight loss in obesity and more than 14% weight loss in diabetes in phase 2. Lange noted zenagamtide’s potential to be “a very competitive drug.”
“The data are actually comparable to what our competitor’s tri-agonist also showed in phase 2,” he said in reference to retatrutide. “So, now we have to see if we can show that in phase 3—and that is ongoing as we speak.”
Beyond zenagamtide, Lange pointed to assets like the triple-G agonist UBT251, as well as cagrilintide, which he framed as being on “the other end of the spectrum.” Novo figures these drugs may eventually fill a niche for patients who are accepting of a lower magnitude of weight loss in favor of a better tolerability profile.
