CagriSema Shows Glycemic And Weight Loss In REIMAGINE 1
Key Takeaways
- Both once-weekly CagriSema dose levels were associated with larger week 40 HbA1c reductions than placebo.
- Both dose levels were also associated with larger relative bodyweight reductions than placebo at week 40.
- Adverse events were more common with active treatment than placebo and were mostly mild or moderate and gastrointestinal related.
REIMAGINE 1 was a randomized, double-blind, parallel-group, phase 3a study conducted at 42 sites 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 once-weekly subcutaneous cagrilintide-semaglutide 2.4 mg each, placebo 2.4 mg plus 2.4 mg, cagrilintide-semaglutide 1.0 mg each, or placebo 1.0 mg plus 1.0 mg for 40 weeks. Randomization used a web-based system with block size six and was stratified by screening HbA1c below 8.5% and MRI substudy participation. Participants, care providers, investigators, and outcome assessors were masked within dose level using visually identical injections. The primary endpoint was change in HbA1c from baseline to week 40 in the full analysis set, and bodyweight change was a prespecified secondary endpoint. Between March 19 and Dec 5, 2024, investigators screened 294 people and enrolled 189; 54% were male, 46% were female, 78% were White, and 14% were Asian. Baseline mean HbA1c was 7.8% and baseline mean BMI was 35.2 kg/m2.
Using the efficacy estimand, estimated mean HbA1c change after 40 weeks was -1.8 percentage points with CagriSema 2.4 mg each, -1.5 with CagriSema 1.0 mg each, and -0.1 with placebo. Treatment differences versus placebo were -1.7 percentage points for 2.4 mg each and -1.3 for 1.0 mg each, both with p<0.0001, with corresponding 95% CIs of -2.0 to -1.3 and -1.8 to -0.9. Estimated mean relative bodyweight change was -13.8%, -11.8%, and -1.4%, with placebo-adjusted differences of -12.4 and -10.4 percentage points; both p<0.0001. The corresponding 95% CIs were -14.7 to -10.1 and -12.9 to -8.0, and both dose levels were superior to placebo on the reported HbA1c and bodyweight endpoints.
The safety analysis included all participants who received at least one dose of trial product. Adverse events occurred in 49 of 62 participants (79%) with 2.4 mg each and 47 of 63 (75%) with 1.0 mg each, compared with 42 of 64 (66%) in the placebo group. Most events were mild or moderate and gastrointestinal related. The study is registered as ClinicalTrials.gov, NCT06323174 and was complete at the time of the abstract.