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Novo Nordisk presents full REIMAGINE results for CagriSema in type 2 diabetes

CagriSema beat semaglutide 2.4 mg on blood sugar and weight in a 2,713-person type 2 diabetes trial, but the HbA1c edge was 0.16 points and the drug is not approved in the US.

By the Semaglutides news desk·

Novo Nordisk presented full results from its phase 3 REIMAGINE 1, 2 and 3 trials of CagriSema in adults with type 2 diabetes on June 7, 2026, at the American Diabetes Association's Scientific Sessions in New Orleans. The data were published at the same time — REIMAGINE 1 and 2 in The Lancet Diabetes & Endocrinology, and REIMAGINE 3 in The Lancet [2].

CagriSema is a once-weekly under-the-skin injection that combines cagrilintide, a long-acting amylin analog, with semaglutide, the GLP-1 receptor agonist sold as Ozempic and Wegovy. It is investigational and not approved in the United States [2][3].

The largest trial, REIMAGINE 2, enrolled 2,713 adults whose type 2 diabetes was not adequately controlled on metformin, with or without an SGLT2 inhibitor [1]. Their average starting HbA1c was 8.2% and average weight was 100.9 kg [1][2]. After 68 weeks, HbA1c fell by 1.91 percentage points with CagriSema 2.4 mg/2.4 mg and by 1.75 points with semaglutide 2.4 mg. The estimated treatment difference was 0.16 percentage points (95% CI -0.27 to -0.05; p=0.0035), which the researchers described as statistically significant [1]. Weight fell 14.2% with CagriSema and 10.2% with semaglutide 2.4 mg, while the placebo group saw HbA1c rise 0.09 points and weight fall 1.5% [2].

REIMAGINE 1 tested CagriSema against placebo in 189 adults managing diabetes with diet and exercise alone. Over 40 weeks, HbA1c fell 1.8 points and weight 13.8% with CagriSema 2.4 mg/2.4 mg, compared with 0.1 points and 1.4% with placebo [2]. An ADA roundup described the trial as showing A1c reductions up to 1.8% and about 14% weight loss in drug-naive adults with type 2 diabetes [4].

REIMAGINE 3 enrolled 274 adults taking basal insulin, with or without metformin, whose average starting HbA1c was 8.8%. Over 40 weeks, CagriSema 2.4 mg/2.4 mg lowered HbA1c by 2.33 points and weight by 12.0%, versus 0.66 points and a 1.1% weight gain with placebo [2].

Side effects were mostly gastrointestinal. In REIMAGINE 2, GI events were reported by 405 of 603 people (67.2%) taking CagriSema 2.4 mg/2.4 mg, 326 of 605 (53.9%) taking semaglutide 2.4 mg, and 42 of 149 (28.2%) taking placebo. Treatment was stopped because of side effects by 51 of 603 (8.5%), 40 of 605 (6.6%), and 2 of 149 (1.3%), respectively [2]. The REIMAGINE 2 authors wrote that the safety profile was consistent with the GLP-1 receptor agonist class and with earlier cagrilintide data [1]. A correction notice for the REIMAGINE 2 paper has also been published in The Lancet Diabetes & Endocrinology [1].

"It was particularly encouraging to see these results consistently demonstrated across the REIMAGINE trials in adults with type 2 diabetes at various stages of their disease, from first-line therapy to add-on to basal insulin," said Martin Holst Lange, Novo Nordisk's chief scientific officer [2]. John B. Buse of the UNC Diabetes Care Center said the combination "may potentially offer meaningful benefits for patients who may need a different approach to managing their type 2 diabetes" [2]. Novo Nordisk funded the trials [1].

Why it matters for patients

CagriSema is not approved in the US, so it cannot be prescribed now [3]. If it is approved, the REIMAGINE 2 numbers suggest its blood sugar advantage over semaglutide 2.4 mg would be small — 0.16 percentage points, statistically significant but narrow [1]. The weight difference was wider: 14.2% versus 10.2% over 68 weeks [2]. Semaglutide 2.4 mg is the Wegovy injection dose; Ozempic is labeled at 0.5 mg, 1 mg or 2 mg [3]. More people taking CagriSema reported gastrointestinal side effects and stopped treatment than people taking semaglutide 2.4 mg [2]. Pricing, insurance coverage, and any US approval for type 2 diabetes have not been disclosed [2][3].

What happens next

Novo Nordisk filed a New Drug Application with the FDA in December 2025 for CagriSema for weight management, with a decision expected in the fourth quarter of 2026 [2]. No FDA filing for a type 2 diabetes indication has been disclosed [2][3]. Novo Nordisk also lists REIMAGINE 4 and REIMAGINE 5, which compared CagriSema 2.4 mg/2.4 mg and 1 mg/1 mg with tirzepatide in adults with type 2 diabetes on standard of care; results from those two trials were not disclosed in the ADA announcement [2].

Sources

  1. https://pubmed.ncbi.nlm.nih.gov/42251859/
  2. https://www.prnewswire.com/news-releases/novo-nordisks-cagrisema-2-4-mg--2-4-mg-demonstrated-significant-reduction-in-hba1c-and-weight-across-multiple-studies-in-the-reimagine-program-presented-at-ada-2026--302793443.html
  3. https://www.prnewswire.com/news-releases/novo-nordisk-advances-cardiometabolic-pipeline-with-new-data-featuring-cagrisema-and-zenagamtide-at-the-american-diabetes-associations-2026-scientific-sessions-302783110.html
  4. https://www.medscape.com/viewarticle/ada-2026-updates-obesity-management-2026a1000g9f

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