CagriSema's Diabetes Trials Read Out: What REIMAGINE 1, 2 and 3 Found
Published: September 30, 2026 · 3 min read · By Grey Peptides News Desk · ✓ Sourced
CagriSema's three type 2 diabetes trials have published. The largest, REIMAGINE 2, enrolled 2,713 people and beat semaglutide 2.4 mg on HbA1c by 0.16 percentage points, a statistically significant margin that is small in clinical terms. The two smaller trials, against placebo, cut HbA1c by 1.8 and 2.3 points. None of this is the obesity filing FDA is reviewing, and none of it is a head-to-head against tirzepatide.
Three trials, three different questions
CagriSema combines cagrilintide, an amylin analogue, with semaglutide, the GLP-1 agonist in Ozempic and Wegovy. Its obesity programme, REDEFINE, is what Novo Nordisk filed with FDA. REIMAGINE is the separate programme in type 2 diabetes, and its first three trials published in 2026, each asking something different: what the combination does in people managing diabetes with diet and exercise alone, how it compares with its own two components, and whether it helps when added to basal insulin.
REIMAGINE 2: the comparison that matters
This is the large one. 2,713 people with inadequately controlled type 2 diabetes on metformin were randomised across six arms for 68 weeks, including the combination at 2.4 mg of each component, semaglutide 2.4 mg alone, and cagrilintide 2.4 mg alone. The primary endpoint compared the combination against semaglutide. HbA1c fell 1.91 percentage points on the combination against 1.75 on semaglutide, a difference of 0.16 points. It cleared statistical significance at p=0.0035, and it is a narrow margin for a two-drug combination over one of its own halves. Adverse events were reported by 86.9% on the combination and 81.2% on semaglutide.
The two placebo trials
REIMAGINE 1 enrolled 189 people whose diabetes was inadequately controlled on diet and exercise alone. Over 40 weeks HbA1c fell 1.8 percentage points on the 2.4 mg combination against 0.1 on placebo, and weight fell 13.8% against 1.4%. REIMAGINE 3 added the combination to basal insulin in 274 people: HbA1c fell 2.33 points against 0.66 on placebo over 40 weeks, with weight reductions of 10 to 12% and no severe hypoglycaemia reported. Both trials met their primary endpoint, and in both the adverse events were mostly mild or moderate gastrointestinal effects.
What this does and does not settle
These are diabetes trials. The application FDA is reviewing is for weight management and rests on REDEFINE, a different programme in a different population. The margin over semaglutide in REIMAGINE 2 is real and small, which is the number to hold onto when the combination is described as a clear step up from semaglutide alone. And none of these three trials compared CagriSema with tirzepatide; any ranking against it remains indirect.
Related on Grey Peptides
The REDEFINE trials, the filing and the regulatory timeline. Cagrilintide encyclopedia entry
The amylin analogue that makes up half the combination. Semaglutide encyclopedia entry
The other half, and the comparator REIMAGINE 2 measured against.
PubMed - REIMAGINE 2 (Lancet Diabetes Endocrinology, 2026), PMID 42251859
Read September 30, 2026. REIMAGINE 1 is PMID 42251860 and REIMAGINE 3 is PMID 42251856; all three abstracts, their registration numbers and every figure quoted here were read on PubMed the same day.