CagriSema vs tirzepatide edge at low doses leads Novo Q3 update as neuropathy data emerge

Novo Nordisk used its third quarter results on 4 November to recast the CagriSema vs tirzepatide question in its own favour. The company leaned on the Phase 3 REIMAGINE 5 trial, in which its amylin and GLP-1 combination produced more weight loss than Eli Lilly's tirzepatide in type 2 diabetes, with both drugs at lower doses. It also showed Phase 2 pain data in diabetic nerve damage and said Phase 3 work there starts in 2027. CagriSema stays filed for obesity in the US, with an FDA decision expected this quarter.

REIMAGINE 5 puts CagriSema ahead at lower doses

REIMAGINE 5 enrolled adults with type 2 diabetes whose blood sugar was not controlled on metformin, an SGLT2 inhibitor or both. They took weekly CagriSema at its lower strength or tirzepatide at a low dose for 60 weeks. According to Novo's topline release from 21 September, CagriSema produced an estimated mean weight loss of 12.4%, against 9.1% for tirzepatide, a gap of 3.3 percentage points that met the test for superiority. HbA1c, the other primary endpoint, fell by 1.71 points with CagriSema and 1.67 points with tirzepatide, which Novo calls non inferior. Both figures use the efficacy estimand, which assumes people stayed on treatment as planned. Mean baseline BMI was 37.2 and mean baseline HbA1c was 8.1%.

Novo framed the CagriSema vs tirzepatide result around how the Lilly drug is used in practice. Its slides cite IQVIA data showing that about half of global tirzepatide volume sits at the dose tested in the trial or below it, and research chief Martin Holst Lange argued on the call that this makes the comparison clinically relevant, according to AllSci's report. Novo also said the trial will support its type 2 diabetes submission for CagriSema, now planned for the second half of 2027 after the REDEFINE 3 cardiovascular outcomes trial reads out, with a launch expected in 2028. On the diabetes case so far, our earlier pooled analysis of six trials found a clear weight edge over semaglutide alone but little extra HbA1c gain.

Why the low dose win has limits

The comparison flatters CagriSema less than the headline suggests. REIMAGINE 5 set a lower CagriSema strength against a low tirzepatide dose, not against the higher doses that many patients climb to. In February, the open label REDEFINE 4 trial tested the top doses of both drugs in 809 people with obesity over 84 weeks. There, CagriSema produced 23.0% weight loss against 25.5% for tirzepatide on the efficacy estimand, and it missed its primary goal of showing non inferiority, Novo said in a filing with the SEC. Taken together, REIMAGINE 5 shows CagriSema beating tirzepatide at the low end of the dose range, while REDEFINE 4 showed it falling short at the top.

Taken together, REIMAGINE 5 shows CagriSema beating tirzepatide at the low end of the dose range, while REDEFINE 4 showed it falling short at the top.

The two trials also differ in population and design, so their numbers do not stack neatly. REIMAGINE 5 enrolled people with diabetes, who tend to lose less weight on incretin drugs than people without it. The September release and the REIMAGINE 5 slides give no side effect or dropout figures, and the full results have not been published in a journal. The practical question for prescribers is whether the CagriSema vs tirzepatide gap matters most at moderate doses or at maximum effect. Novo is pressing the first framing, while Lilly's own tirzepatide sales show the rival brand still growing fast. A peer reviewed paper with safety tables would let outside experts judge how meaningful the gap is.

Painful diabetic neuropathy opens a new front

The newer signal is pain. In a Phase 2 trial of 141 people with type 2 diabetes and painful diabetic neuropathy, the higher CagriSema strength was added to standard care and compared with placebo. Mean pain intensity score at baseline was 6.4, and CagriSema lowered it by 2.4 points against 1.3 points for placebo, according to the Q3 investor presentation. That drop is the source of the roughly 38% reduction quoted in reports of the call, but it is a change from baseline; the gap over placebo was about 1.1 points. More than 53% of people on CagriSema reached at least a 30% cut in pain, a threshold pain researchers often treat as meaningful, though the slide gives no placebo rate for it.

Novo says people on CagriSema also reported better quality of life and sleep, and that safety matched earlier CagriSema trials. The company plans Phase 3 trials in painful diabetic neuropathy across its portfolio during 2027, which suggests the effort may not be limited to CagriSema. Its slides state that about a quarter of people with diabetes are affected, and that more than 20% of US patients with the condition start opioids on top of standard care. The materials do not explain why a weight loss drug would ease nerve pain. Weight loss, better glucose control and direct nerve effects are all possible, and a trial of this size cannot separate them. The placebo group's own drop of 1.3 points shows how strong placebo effects can be in pain studies.

Filing timeline and the wider Novo pipeline

On the business side, Novo Nordisk Q3 2026 results showed adjusted sales of DKK 79.2 billion, up 4% at constant exchange rates. The company raised its 2026 outlook for adjusted sales growth and adjusted operating profit growth to a range of minus 2% to plus 2% at constant rates. CagriSema sits at the centre of that plan. Novo filed it with the FDA for weight management in December 2025 and expects a decision in the fourth quarter of 2026, with a full US launch at the start of 2027 if it is approved. Chief executive Maziar Doustdar named CagriSema and the hemophilia A drug Frehemgo as the next major launches, according to AllSci. All of these dates are company plans, not certainties.

Behind CagriSema, Novo is widening its obesity bets. Oral zenagamtide, which the slides describe as a unimolecular oral dual agonist, has entered the Phase 3 AMAZE 9 trial. Amylin 355, in oral and injectable forms, began a Phase 2 trial that the slides show with 170 people over 26 weeks, and results are due in the second half of 2027. An oral ACSL5 inhibitor, a small molecule that does not act on GLP-1, has Phase 1 results expected in the same window, and Lange said it could offer double digit weight loss without dose titration, according to AllSci. Lilly is building its own amylin pairing, with EloraTZP Phase 3 trials registered, so this amylin race will not turn on CagriSema alone.

Conclusion

REIMAGINE 5 gives Novo a clean superiority result in the CagriSema vs tirzepatide contest, but only at lower doses, and it sits beside a REDEFINE 4 miss at the top doses. The neuropathy data are early and need Phase 3 confirmation in larger trials. CagriSema stays filed on our board, and the FDA decision expected this quarter is the event that would move it. This report is for research context and is not medical advice.