The cagrilintide development path breaks into several stages: molecular optimisation, early clinical work, the Phase III programme, regulatory submission, and the 2026 developments. Here is the chronological breakdown.
[Molecular origin: AM833]
The development code was AM833. Novo Nordisk's chemists did two things: stabilise the amylin sequence to prevent aggregation into amyloid fibrils, and attach a fatty acid chain so the peptide binds albumin in circulation (Kruse et al., 2021, PMID 34288673).
The result was a half-life extended to 159–195 hours, roughly one week, enabling once-weekly dosing (Enebo et al., 2021, PMID 33894838).
[Early clinical: Phase Ib and Phase II]
Phase Ib: 96 adults, cagrilintide 0.16–4.5 mg combined with semaglutide 2.4 mg, 20 weeks. The cagrilintide 2.4 mg arm lost 17.1% versus 9.8% for semaglutide plus placebo (Enebo et al., 2021, PMID 33894838).
Phase II monotherapy: 706 adults without diabetes, five cagrilintide doses versus placebo, 26 weeks. Weight loss 6.0–10.8% versus 3.0% on placebo. The 4.5 mg arm beat 3.0 mg liraglutide (10.8% vs 9.0%) (Lau et al., 2021, PMID 34798060).
Phase II diabetes: 92 adults with type 2 diabetes, CagriSema versus components, 32 weeks. CagriSema lost 15.6%, cagrilintide 8.1%, semaglutide 5.1% (Frias et al., 2023, PMID 37364590).
[Phase III programme: the REDEFINE series]
REDEFINE 1: 3,417 adults without diabetes, 68 weeks. CagriSema 20.4%, semaglutide 14.9%, cagrilintide 11.5%, placebo 3.0% (Garvey et al., 2025, NEJM, PMID 40544433).
REDEFINE 2: 1,206 adults with type 2 diabetes, 68 weeks. Weight loss 13.7% vs 3.4% on placebo; 73.5% of participants reached HbA1c of 6.5% or lower (Davies et al., 2025, NEJM, PMID 40544432).
REIMAGINE 2: 2,713 adults with type 2 diabetes, CagriSema vs semaglutide vs cagrilintide, 68 weeks. HbA1c fell 1.91 percentage points vs 1.75 for semaglutide alone (Buse et al., 2026, PMID 42251859).
[Regulatory submission]
On 18 December 2025, Novo Nordisk submitted the CagriSema NDA to the FDA, based on REDEFINE 1 and REDEFINE 2 data. A decision is expected in 2026.
If approved, cagrilintide would be available only as a component of CagriSema, delivered via injection pen. Novo Nordisk has no plan for a standalone cagrilintide product.
[Key 2026 milestones]
23 February: REDEFINE 4 results announced. 809 adults with obesity, CagriSema vs tirzepatide 15 mg, 84 weeks. 23.0% vs 25.5%, failing non-inferiority. This is the only direct obesity comparison between CagriSema and tirzepatide. Not yet formally published.
31 March: the FDA issued warning letters to online vendors selling cagrilintide.
31 May: the FDA had cumulatively recorded 990 compounded semaglutide and more than 730 compounded tirzepatide adverse event reports.
1 September: the FDA updated its statement, specifying that "retatrutide and cagrilintide cannot be used in compounding under federal law."
15 September: Nature Metabolism published the rat study showing cagrilintide plus retatrutide beat either drug alone and equivalent-dose comparators in obese rats (Petersen et al., 2026, PMID 42744908).
21 September: two new Phase III readouts. REIMAGINE 5: type 2 diabetes, CagriSema 1 mg / 1 mg vs tirzepatide 5 mg, 60 weeks, 12.4% vs 9.1% weight loss. REDEFINE 9: without diabetes, CagriSema 1 mg / 1 mg vs placebo, 68 weeks, 21% vs 2%. Both are company announcements, not yet formally published.
[Unpublished results]
REDEFINE 4, REIMAGINE 5 and REDEFINE 9 currently exist only as company earnings summaries, not peer-reviewed papers. Treat those numbers with caution until publication.
[What the timeline shows]
The development path is clear: molecular optimisation solved the half-life problem, early clinical work confirmed weight loss, Phase III confirmed the combination's value, and the regulatory submission is under review.
But three gaps run through the timeline: no independent replication — every human trial was Novo Nordisk-funded; no human data for cagrilintide plus retatrutide; and no safety data beyond 84 weeks.
The timeline continues. The next milestone is the FDA's decision on CagriSema, expected in 2026.