Full REIMAGINE 1-3 CagriSema results presented at ADA 2026 and published

Novo Nordisk presented the full phase 3 REIMAGINE 1–3 results for CagriSema — a fixed-dose combination of the amylin analog cagrilintide and the GLP-1 drug semaglutide — on June 7, 2026, during a late-breaking symposium at the American Diabetes Association Scientific Sessions in New Orleans ^[2]. REIMAGINE 1 and 2 were published simultaneously in The Lancet Diabetes & Endocrinology and REIMAGINE 3 in The Lancet ^[2]. All three trials met their primary HbA1c endpoint and their confirmatory secondary weight endpoints ^[2].

The headline trial, REIMAGINE 2, randomized 2,713 adults across 30 countries who had type 2 diabetes inadequately controlled on metformin, with or without an SGLT2 inhibitor ^[1]. Participants received once-weekly CagriSema (2.4 mg of each component), semaglutide 2.4 mg, cagrilintide 2.4 mg alone, CagriSema 1 mg/1 mg, semaglutide 1 mg, or placebo for 68 weeks ^[1]. Mean baseline HbA1c was 8.2% and mean baseline weight was 100.9 kg ^[1][2]. Of those randomized, 95.7% completed the study and 87.6% were still on treatment at week 68 ^[1].

A statistically significant but small glucose difference

Using the efficacy estimand — which models what would happen if everyone stayed on treatment and added no other glucose-lowering drugs — CagriSema 2.4/2.4 mg lowered HbA1c by 1.91 percentage points versus 1.75 for semaglutide 2.4 mg, an estimated treatment difference of 0.16 percentage points (95% CI -0.27 to -0.05; p=0.0035) ^[1]. Under the treatment regimen estimand, which counts results regardless of whether people stayed on drug, the gap was 1.80 versus 1.68 points (p=0.028) ^[2].

The weight difference was larger. CagriSema 2.4/2.4 mg cut body weight by 14.2% versus 10.2% with semaglutide 2.4 mg (p<0.0001), or 12.9% versus 9.2% under the treatment regimen estimand ^[2]. Cagrilintide alone reduced HbA1c by 0.80 points and weight by 8.4%, while pooled placebo groups saw HbA1c rise 0.09 points ^[2].

Side effects tracked the pattern seen with GLP-1 drugs. Any adverse event was reported in 86.9% of the CagriSema 2.4/2.4 mg group versus 81.2% on semaglutide 2.4 mg ^[1]. Gastrointestinal events were most common: 67.2% with CagriSema 2.4/2.4 mg, 53.9% with semaglutide 2.4 mg, and 28.2% with placebo ^[2]. Discontinuations due to adverse events were 8.5% versus 6.6%, respectively ^[2]. Investigators concluded the safety profile was consistent with the GLP-1 class and prior cagrilintide data ^[1]. A correction to the Lancet Diabetes & Endocrinology paper was published online June 19, 2026 ^[1].

The two smaller trials tested different patient groups. REIMAGINE 1 enrolled 189 adults controlled only by diet and exercise; over 40 weeks, CagriSema 2.4/2.4 mg cut HbA1c 1.8 points and weight 13.8% versus 0.1 points and 1.4% with placebo ^[2]. REIMAGINE 3 enrolled 274 adults adding CagriSema to once-daily basal insulin; at 40 weeks HbA1c fell 2.33 points and weight 12.0%, versus 0.66 points and a 1.1% weight gain on placebo ^[2].

Why it matters for patients

For people with type 2 diabetes who are already on a GLP-1 drug, the practical question is whether adding amylin buys much. On blood sugar, the measured edge over semaglutide 2.4 mg in REIMAGINE 2 was 0.16 percentage points of HbA1c — real statistically, but small ^[1]. The weight difference of about 4 percentage points was larger ^[2]. Those gains came with more stomach and bowel side effects and somewhat more people stopping treatment ^[2].

CagriSema is not approved in the United States, and its safety and efficacy for these uses are not established ^[3]. None of these trials compared CagriSema against tirzepatide; Novo says REIMAGINE 4 and 5 did that, but those results are not in the materials released here ^[2]. Cardiovascular outcome data for CagriSema are also not reported in these sources.

What happens next

Novo Nordisk filed a U.S. New Drug Application in December 2025 for CagriSema for weight management, with an FDA decision expected in the fourth quarter of 2026 ^[2]. The sources do not state when, or whether, a separate type 2 diabetes application will be filed. One ADA commentator, Neda Rasouli, MD, of the University of Colorado, highlighted REIMAGINE 1's roughly 14% weight loss and A1c reductions up to 1.8% in drug-naive adults as among the meeting's notable findings ^[4].