Novo Nordisk announced this morning that CagriSema, its investigational combination of semaglutide and a second hormone, beat tirzepatide on weight loss in a head-to-head phase 3 trial in adults with type 2 diabetes: an estimated 12.4% against 9.1% at week 60. A second phase 3 trial put CagriSema at 21.0% weight loss against 2.0% on placebo in adults with overweight or obesity. Both numbers come from a company topline announcement delivered to investors, not from a peer-reviewed paper — and the tirzepatide comparison arm was dosed at 5 mg, which is not the maximum dose.
What the two trials reported
REIMAGINE 5 was a phase 3 trial in adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor, or both. It compared once-weekly CagriSema 1.0 mg/1.0 mg against tirzepatide 5 mg, with dual primary endpoints of change in HbA1c and relative change in body weight from baseline to week 60. On weight, CagriSema was superior: 12.4% versus 9.1%. On blood sugar it was non-inferior rather than superior — an HbA1c reduction of 1.71% against tirzepatide’s 1.67%, a gap of four hundredths of a percentage point.
REDEFINE 9 was a phase 3 trial in adults with overweight or obesity, run as an adjunct to a reduced-calorie diet and increased physical activity. Novo says it investigated both CagriSema 1.7 mg/1.7 mg and 1.0 mg/1.0 mg against placebo, with primary endpoints of relative weight change and the proportion of participants reaching at least 5% weight reduction by week 68. The announced result is for the 1.0 mg/1.0 mg dose: 21.0% weight loss against 2.0% on placebo, with the superiority endpoint met, plus greater improvements than placebo in systolic blood pressure, waist-to-height ratio and fasting lipids. The company describes CagriSema as well tolerated in both trials, with a safety profile consistent with previous studies.
CagriSema is a fixed-dose combination of cagrilintide, a long-acting amylin receptor agonist, and semaglutide, the GLP-1 receptor agonist sold as Wegovy and Ozempic. Amylin is a separate appetite-regulating hormone, so the combination works on two pathways rather than one. It is not approved anywhere. Novo filed a New Drug Application with the FDA in December 2025 for weight management and says a decision is expected in the fourth quarter of 2026.
The dose at the centre of the comparison
The headline is that CagriSema beat tirzepatide. The qualifier is which tirzepatide. Tirzepatide is prescribed up to 15 mg for both weight management and type 2 diabetes; the arm it lost to here was 5 mg. A 3.3-point win over a low-to-middle dose does not establish how CagriSema 1.0/1.0 would fare against tirzepatide at 10 or 15 mg, and the announcement does not claim it does. Novo addresses the point directly, arguing that treatment is individualised and that not all patients receive or remain on the highest available dose — a reasonable observation about real-world prescribing, and also an argument for the comparison rather than evidence about the drugs at full strength. Readers who followed SURMOUNT-5, where tirzepatide and semaglutide were compared at their maximum tolerated doses, are looking at a different kind of trial here; our comparison of the two approved drugs covers that head-to-head.
One more piece of small print carries weight. Every efficacy figure in the release is asterisked to an “efficacy estimand.” That is a statistical framing which estimates what the drug does in people who stay on it and take it as directed, setting aside what happens after someone stops or adds another medication. The alternative framing, a treatment-policy estimand, counts everybody as randomised regardless of what they did next, and typically produces smaller numbers. Both are legitimate; they answer different questions. The 12.4% and 21.0% describe the drug taken as intended, not the average outcome across everyone who started it.
What is not yet known
This is a company topline announcement made at an investor briefing, and it has not been peer-reviewed or published. It gives no participant numbers for either trial, no confidence intervals around any estimate, no discontinuation rates, and no adverse-event figures beyond the assurance that tolerability was consistent with earlier studies — which matters, because gastrointestinal side effects and dropout are where combination therapies have historically been judged. REDEFINE 9 tested a 1.7 mg/1.7 mg arm as well, and no result for it appears in the release. REDEFINE 9 had no active comparator, so its 21.0% cannot be set against tirzepatide or against semaglutide alone. And nothing here is a regulatory decision: CagriSema remains investigational, with an FDA determination on the weight-management application still pending.
Sources: Novo Nordisk A/S. “Novo’s CagriSema delivers superior weight loss versus tirzepatide in REIMAGINE 5 trial.” Company announcement, Bagsværd, Denmark, 21 September 2026. Topline results; not peer-reviewed.
