Novo, Lilly trade oral GLP-1 data readouts at ECO

The head-to-head rivalry between Novo Nordisk and Eli Lilly in oral GLP-1 agonists for weight loss has come to the fore this week, with both companies presenting new data at the European Congress on Obesity in Türkiye.

Novo Nordisk gave an update on the OASIS 4 trial of its Wegovy (semaglutide) pill, including a sub-analysis that showed it was able to deliver nearly 22% weight loss in a group of early responders to the therapy.

The pattern mirrored the result of a trial of its high-dose injectable formulation of Wegovy, reported earlier at ECO, which also identified a subgroup of early responders who achieved dramatic 28% weight loss at 72 weeks.

In OASIS 4, 28.8% of patients achieved 10% or greater loss in weight at week 16, and this group went on to lose 21.6% by week 64. The other group of non-early responders lost 11.5% by the end of the follow-up period, which Novo Nordisk said was also "clinically meaningful," but the results add to the evidence of variable responses to GLP-1 therapies among patients.

As with the high-dose Wegovy trial analysis, which found benefits on abdominal fat and little impact on lean muscle mass, Novo Nordisk looked at secondary clinical endpoints in OASIS 4. It found that 77.3% of people taking oral Wegovy who had poor physical function at the start of the trial saw improvements in their ability to move – including bending over, standing comfortably, and staying active – which was around twice the rate seen in the placebo arm (42.9%).

Novo Nordisk also presented additional data at ECO from the ORION study, an indirect comparison between oral Wegovy and Lilly's rival Foundayo (orforglipron), claiming that its drug delivers greater weight loss, while Foundayo-treated patients are 14 times more likely to discontinue treatment due to side effects.

Oral Wegovy reached the market first, with a launch that Novo Nordisk says has broken records for a GLP-1 weight-loss therapy, with sales approaching $350 million in its first quarter on the market. Foundayo's trajectory seems to be slower, based on its first few weeks on sale, although, Lilly has said it is too early to say which product will eventually win the marketing battle.

Foundayo maintenance data

Lilly's presentations at ECO focused on the use of Foundayo to maintain weight loss after initial treatment with either its injectable GIP/GLP-1 agonist Zepbound (tirzepatide) – which outperformed standard-dose Wegovy in head-to-head trials and has now overtaken Novo Nordisk's drug in global sales terms – or injectable Wegovy.

The ATTAIN-MAINTAIN trial found that patients who switched from either of the injectables to Foundayo or a low-dose Zepbound shot maintained almost all their prior weight loss over 52 weeks – all but 0.9 kg in the case of Zepbound and 5.0 kg with Foundayo.

Meanwhile, the SURMOUNT-MAINTAIN trial also showed that most of the weight loss achieved with Zepbound was retained when the low-dose formulation was used as maintenance.

The studies address one of the main challenges in obesity care, which is preventing people from regaining weight after their initial treatment with injectables comes to an end, and point to a role for oral therapies in achieving that objective.

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