Efficacy and safety of once-weekly cagrilintide每semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a studyDr Vanita R Aroda, MD[url=]a[/url] Send email to [email protected] ∙ Raffaella Buzzetti, MD[url=]b[/url] ∙ Stine-Mathilde Dalskov, MD[url=]c[/url] ∙ Akshay B Jain, MD[url=]d[/url],[url=]e[/url] ∙ Jonas Hughes Larsen, MSc[url=]f[/url] ∙ Chantal Mathieu, MD[url=]g[/url] ∙ et al. Show more
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Published June 7, 2026
DOI: 10.1016/S2213-8587(26)00126-9 External LinkAlso available on ScienceDirect External Link
Copyright: © 2026 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
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SummaryBackgroundCagrilintide每semaglutide (CagriSema) is a novel, once-weekly combination of the amylin receptor agonist cagrilintide and the GLP-1 receptor agonist semaglutide. We aimed to assess the efficacy and safety of cagrilintide每semaglutide for people with type 2 diabetes inadequately controlled with diet and exercise.
MethodsREIMAGINE 1 was a randomised, double-blind, parallel-group, phase 3a study carried out at 42 sites (study sites included university hospitals, health-care centres, research centres, and other centres) in six countries. Adults aged 18 years or older with type 2 diabetes inadequately controlled with diet and exercise were randomly assigned (2:1:2:1) to receive once-weekly subcutaneous cagrilintide 2﹞4 mg plus semaglutide 2﹞4 mg (cagrilintide每semaglutide [2﹞4 mg each]), placebo 2﹞4 mg plus 2﹞4 mg, cagrilintide 1﹞0 mg plus semaglutide 1﹞0 mg (cagrilintide每semaglutide [1﹞0 mg each]), or placebo 1﹞0 mg plus 1﹞0 mg for 40 weeks. Randomisation was done using a web-based system with a block size of six and stratified according to HbA1c less than 8﹞5% at screening and participation in the MRI substudy. Participants, care providers, investigators, and outcome assessors were masked within dose level and all participants received visually identical injections to maintain masking throughout the study. The primary endpoint was change in HbA1c from baseline to week 40 in the full analysis set; safety was assessed in all participants who received at least one dose of the trial product. Change in bodyweight from baseline to week 40 was a prespecified secondary endpoint. This study is registered with ClinicalTrials.gov, NCT06323174, and is complete.
FindingsBetween March 19 and Dec 5, 2024, 294 people were screened for eligibility, 189 of whom were enrolled and randomly assigned to cagrilintide每semaglutide (2﹞4 mg each; n=62), cagrilintide每semaglutide (1﹞0 mg each; n=63), or placebo (n=64). 103 (54%) of 189 were male, 86 (46%) were female, 147 (78%) were White, and 26 (14%) were Asian. Baseline mean HbA1c was 7﹞8% (SD 0﹞7) and BMI was 35﹞2 kg/m2 (7﹞4). Using the efficacy estimand, the estimated mean change in HbA1c after 40 weeks was −1﹞8 percentage points (SE 0﹞1) with cagrilintide每semaglutide (2﹞4 mg each), −1﹞5 percentage points (0﹞1) with cagrilintide每semaglutide (1﹞0 mg each), and −0﹞1 percentage points (0﹞2) with placebo. This corresponded to an estimated treatment difference of −1﹞7 percentage points (95% CI −2﹞0 to −1﹞3; p<0﹞0001) for cagrilintide每semaglutide (2﹞4 mg each) versus placebo and −1﹞3 percentage points (−1﹞8 to −0﹞9; p<0﹞0001) for cagrilintide每semaglutide (1﹞0 mg each) versus placebo. Cagrilintide每semaglutide was superior to placebo with respect to estimated mean relative change in bodyweight from baseline to week 40 for cagrilintide每semaglutide (2﹞4 mg each; −13﹞8% [SE 1﹞0]) versus placebo (−1﹞4% [0﹞7]; estimated treatment difference −12﹞4 percentage points [95% CI −14﹞7 to −10﹞1]; p<0﹞0001) and cagrilintide每semaglutide (1﹞0 mg each; −11﹞8% [1﹞0]) versus placebo (−1﹞4% [0﹞7]; estimated treatment difference −10﹞4 percentage points [−12﹞9 to −8﹞0]; p<0﹞0001). Adverse events were reported by 49 (79%) of 62 participants in the cagrilintide每semaglutide (2﹞4 mg each) group, 47 (75%) of 63 in the cagrilintide每semaglutide (1﹞0 mg each) group, and 42 (66%) of 64 in the placebo group. Most adverse events were mild or moderate and gastrointestinal related.
InterpretationIn a population of people with early-stage type 2 diabetes inadequately controlled with diet and exercise, cagrilintide每semaglutide (2﹞4 mg each and 1﹞0 mg each) was superior to placebo in reducing HbA1c. The safety profile was consistent with the GLP-1 receptor agonist class and previous safety data for cagrilintide. These findings support cagrilintide每semaglutide as a potential novel and effective therapeutic intervention for people with early-stage type 2 diabetes.
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