Novo's CagriSema Beats Tirzepatide 5 mg on Weight Loss

Head-to-Head Win in REIMAGINE 5

Participants received CagriSema 1.0 mg/1.0 mg or tirzepatide 5 mg, with dual primary end points of change in HbA1C and relative change in body weight from baseline to week 60. At week 60, CagriSema achieved an estimated average weight loss of 12.4%, compared with 9.1% with tirzepatide, meeting the superiority threshold. HbA1C reductions were 1.71% with CagriSema and 1.67% with tirzepatide, confirming noninferiority.

In a head-to-head trial earlier this year, the drug had fallen short of Lilly's Zepbound on weight loss, marking a setback for the Danish drugmaker. In the late-stage study, a 1 mg dose of Novo's drug CagriSema was superior to Lilly's tirzepatide at 5 mg for weight loss.

What CagriSema Is

Novo Nordisk's investigational once-weekly CagriSema produced greater weight loss than tirzepatide 5 mg in adults with type 2 diabetes. CagriSema combines cagrilintide, a long-acting amylin analog, and semaglutide, the GLP-1 component in Wegovy. The 1.0 mg/1.0 mg dose is the low dose being tested for diabetes, with higher 2.4 mg/2.4 mg doses for obesity.

CagriSema also showed greater improvements than placebo across prespecified supportive endpoints, including waist circumference and cardiometabolic markers.

Why the 5 mg Comparator Matters

Lilly's tirzepatide, which is the active ingredient in its diabetes drug Mounjaro and obesity drug Zepbound, showed weight loss of 9.1% at 5 mg. Tirzepatide 5 mg is the starting maintenance dose for diabetes, not the maximal 15 mg obesity dose. Novo chose this low dose to prove superiority in diabetes while keeping HbA1c comparable.

While the low-dose data is encouraging, findings were less impactful given tirzepatide has already been proven superior to higher doses of Novo's CagriSema in obesity in a prior trial, noted BMO analyst Evan Seigerman. That prior trial compared CagriSema 2.4/2.4 mg versus tirzepatide in obesity and favored tirzepatide.

The Other Trial: 21% Weight Loss in Obesity

At the Capital Markets Day, Novo also presented topline results from two Phase 3 trials of CagriSema. In REDEFINE 9, the same 1.0/1.0 mg dose produced 21.0 percent weight loss at week 68 in adults with overweight or obesity, versus 2.0 percent for placebo.

CagriSema 1.0 mg/1.0 mg delivered significant and clinically meaningful weight loss of 21% versus placebo at week 68 in adults living with overweight or obesity in REDEFINE 9. In both trials, CagriSema was well tolerated overall, with a safety profile consistent with previous studies.

Market Reaction and Strategic Context

Novo shares plunge 6% despite CagriSema beating Lilly in diabetes trial, as investors focused on the fact the win was at low dose and that CagriSema had previously lost to Zepbound at higher doses. At Novo's capital markets day on Monday, the company outlined a multi-year plan for its next-generation obesity injectables, aiming for an early next-year launch of CagriSema combination.

"The results from CagriSema are very encouraging, demonstrating the strong potency of the combination of semaglutide and cagrilintide. With only 1.0 mg/1.0 mg, CagriSema shows superior weight loss versus tirzepatide 5 mg as well as strong results across obesity and type 2 diabetes," said Martin Holst Lange, executive vice president R&D and chief scientific officer at Novo.

What This Means for Prescribers

Novo Nordisk today announced topline results from the phase 3 REIMAGINE 5 and REDEFINE 9 trials of once-weekly CagriSema, an investigational product. For type 2 diabetes patients where weight loss is a priority, low-dose CagriSema beats low-dose tirzepatide on weight while matching glucose lowering, offering a potential alternative if launched in diabetes first.

For obesity, the 21% placebo-adjusted loss at low dose suggests higher 2.4/2.4 mg could approach 25-27% range, competitive with retatrutide and tirzepatide, pending full REDEFINE program.

Next Steps and Filing Timeline

Novo plans filing in early 2026 for CagriSema, targeting launch early next year. Safety profile consistent with GLP-1 plus amylin: nausea, vomiting and injection site reactions, but no new signals. Investors await REDEFINE 1 and 2 results at full dose to judge obesity competitiveness versus Lilly's triple agonist pipeline.

Working Source Links:

CagriSema Tops Tirzepatide 5 mg for Weight Loss in REIMAGINE 5 - https://www.pharmacytimes.com/view/cagrisema-tops-tirzepatide-5-mg-for-weight-loss-in-reimagine-5

Novo's CagriSema Outshines Lilly in Diabetes Weight Loss Trials - https://pharma.economictimes.indiatimes.com/news/research-and-development/novo-says-cagrisema-tops-lilly-rival-in-diabetes-patients-for-weight-loss/134404726

Novo's CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial - GlobeNewswire - https://beta.manilatimes.net/2026/09/21/tmt-newswire/globenewswire/novos-cagrisema-delivers-superior-weight-loss-versus-tirzepatide-in-reimagine-5-trial/2429306

CagriSema beats tirzepatide as Novo sets 2030 ambitions - Nordic Life Science - https://nordiclifescience.org/cagrisema-beats-tirzepatide-as-novo-sets-2030-ambitions/

CagriSema Shows Greater Weight Loss With Non-Inferior HbA1c Reduction - https://pharmacally.com/cagrisema-greater-weight-loss-tirzepatide-5mg-reimagine-5/