Novo’s Next-Gen Obesity Drug Beats Wegovy On Blood Sugar Control in Phase III

Racing Cars at the finish line

While CagriSema bested Novo Nordisk’s Wegovy on blood sugar control in a late-stage trial, the next-gen weight loss drug still has not met the pharma’s 25% weight loss goal.

Novo Nordisk’s next-generation weight-loss drug CagriSema beat current blockbuster GLP-1 Wegovy at controlling blood sugar in a Phase III trial, while falling below the Danish pharma’s lofty 25% weight loss goal.

In the Phase III REIMAGINE 2 study, which enrolled more than 2,700 adults with type 2 diabetes, Novo tested a 2.4-mg dose of CagriSema delivered via a weekly subcutaneous injection. The company compared that against the same sized doses of semaglutide, the amylin analog cagrilintide alone and placebo. The trial also included a 1-mg dose arm for CagriSema compared with same doses of semaglutide, cagrilintide and placebo.

At 68 weeks, patients treated with 2.4-mg CagriSema saw a 1.91%-point reduction in HbA1c, a measure of average blood sugar over the past two to three months, according to a news release on Monday. HbA1c in patients on semaglutide dropped by 1.76%-points, whereas placebo comparators saw a 0.09%-point increase.

CagriSema’s treatment benefit was significantly stronger than semaglutide’s, Novo said.

Similarly, CagriSema elicited significantly greater weight-loss versus semaglutide. Patients on the investigational treatment lost 14.2% of their body weight at 68 weeks, as opposed to 10.2% in the semaglutide group. CagriSema had not yet shown a weight-loss plateau at the time of readout, Novo said.

Despite stronger weight reduction numbers of CagriSema, the drug still came far below Novo’s own target. In a June 23, 2025 note to investors, analysts at William Blair noted that the pharma had set a “lofty benchmark” of 25% placebo-adjusted weight-loss—a bar that the drug has yet to meet.

The closest Novo has so far come to hitting this target was in December 2024, when CagriSema in the Phase III REDEFINE 1 study elicited a 22.7% drop in body weight at 68 weeks, versus 2.3% in placebo. Topline data from a second study, dubbed REDEFINE 2 and released in March 2025, showed 15.7% weight-loss with CagriSema versus 3.1% in placebo.

Novo in December 2025 nevertheless pushed through with an FDA filing for CagriSema as a weight-loss medicine, proposing weekly use in patients with obesity or who are overweight with at least one related comorbidity. A similar application for diabetes is also planned, according to Monday’s news release, pending data from the REIMAGINE 1 and REDEFINE 3 trials. REIMAGINE 1 tests CagriSema in treating type 2 diabetes while REDEFINE 3 is for controlling cardiovascular disease.

CagriSema is a fixed-dose combination of the GLP-1 receptor agonist semaglutide and the long-acting amylin analog cagrilintide. If approved, the drug “could be the first amylin-based combination therapy” for weight-loss and type 2 diabetes on the market, Martin Holst Lange, Novo’s chief scientific officer, said in a statement on Monday.

Novo is also running a head to head study of CargiSema against Eli Lilly’s tirzepatide, with a readout expected this quarter.

Tristan is an independent science writer based in Metro Manila, with more than eight years of experience writing about medicine, biotech and science. He can be reached at tristan.manalac@biospace.com, tristan@tristanmanalac.com or on LinkedIn.
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