Novo Nordisk says CagriSema 1.0/1.0 mg beat tirzepatide 5 mg on weight loss in Phase 3 REIMAGINE 5

Novo Nordisk announced topline results on September 21, 2026, from the Phase 3 REIMAGINE 5 trial, saying once-weekly CagriSema at 1.0 mg/1.0 mg produced an estimated average weight loss of 12.4% at week 60 in adults with type 2 diabetes, compared with 9.1% for tirzepatide 5 mg ^[1]. The company said CagriSema met the bar for superiority on weight loss and was non-inferior on blood sugar control, with HbA1c reductions of 1.71 percentage points versus 1.67 for tirzepatide ^[1].

CagriSema is a fixed-dose combination of cagrilintide, a long-acting amylin receptor agonist, and semaglutide, the GLP-1 drug sold as Ozempic, Wegovy and Rybelsus ^[1]. Tirzepatide is sold as Mounjaro and Zepbound ^[3]. CagriSema is still investigational and is not approved anywhere ^[1].

An important caveat is built into the trial design: neither drug was tested at its maximum dose. REIMAGINE 5 enrolled about 1,000 adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor or both, and compared CagriSema 1.0 mg/1.0 mg with tirzepatide 5 mg ^[2]. Novo framed that choice around real-world prescribing, saying "not all patients receive or remain on the highest available dose of current therapies" ^[1]. The percentages come from what Novo calls the efficacy estimand, which estimates results as if everyone stayed on treatment ^[1]. Novo's description of the trial lists it as a 68-week study, while the results announcement reports the dual primary endpoints at week 60 ^[1][2].

Novo also reported results from REDEFINE 9, in adults with overweight or obesity without diabetes. CagriSema 1.0 mg/1.0 mg produced a 21.0% weight reduction at week 68 versus 2.0% for placebo, hitting the primary superiority endpoint, with greater improvements than placebo in systolic blood pressure, waist-to-height ratio and fasting lipids ^[1]. That trial also included a 1.7 mg/1.7 mg arm; results for that dose were not included in the announcement ^[1]. Novo said CagriSema was "well tolerated overall" in both trials, with a safety profile consistent with previous studies, but did not release side-effect rates ^[1].

Why it matters for patients

Head-to-head data are unusual in this drug class, and they shape how doctors and insurers compare options. But the comparison here is between low doses, so it does not answer the question most patients ask: which drug works better at the doses people actually build up to.

The backdrop matters. In February 2026, Novo reported that CagriSema missed in the open-label REDEFINE 4 study, where patients on CagriSema lost 20.2% of body weight over 84 weeks versus 23.6% on tirzepatide, a result that failed to show non-inferiority ^[3]. Novo shares fell more than 12% in Copenhagen that day ^[3]. A separate diabetes head-to-head, REIMAGINE 4, pits CagriSema 2.4 mg/2.4 mg against tirzepatide 15 mg in about 1,000 adults ^[2]; results from that trial have not been reported here.

Earlier diabetes data showed CagriSema 2.4 mg/2.4 mg cut HbA1c by 1.91 percentage points and body weight by 14.2% at week 68, beating semaglutide 2.4 mg on both measures in REIMAGINE 2, a 2,728-person trial ^[2]. In that study, 43% of people on the higher CagriSema dose lost at least 15% of body weight and 24% lost at least 20% ^[2]. Gastrointestinal side effects were the most common, and most were mild to moderate and eased over time ^[2].

One practical note: these are company topline summaries, not peer-reviewed publications. Detailed REIMAGINE 2 results are slated for a scientific conference in 2026 ^[2], and Novo said more detail on other data would come later ^[1].

What happens next

Novo filed a New Drug Application with the U.S. Food and Drug Administration in December 2025 for CagriSema for weight management, based on the REDEFINE 1 and REDEFINE 2 trials ^[1][2]. The company says an FDA decision is expected in the fourth quarter of 2026 ^[1]. For type 2 diabetes, Novo has said it will approach regulators to discuss a pathway ^[2]; no filing date for that use has been disclosed. Pricing, insurance coverage and whether the 1.0 mg/1.0 mg dose would be marketed have not been announced.