CagriSema Add-On to Basal Insulin Meets Phase 3 Endpoints

Key Takeaways

• Both weekly cagrilintide-semaglutide dose levels met the primary endpoint and were associated with greater HbA1c lowering than placebo by week 40.
• Bodyweight reductions of 10% to 12% were reported across the active-dose groups.
• Adverse events were mostly mild to moderate gastrointestinal disorders, no severe hypoglycaemia was reported, and one death in the 1.0 mg group was considered unrelated to treatment because of malignancy.

In REIMAGINE 3, adults with type 2 diabetes already receiving stable basal insulin had larger HbA1c reductions with weekly cagrilintide-semaglutide than with placebo over 40 weeks. The higher-dose regimen lowered HbA1c by about 2.3 percentage points by week 40, the larger reduction in this basal insulin-treated group. Bodyweight reductions of roughly 10% to 12% were also reported across the active-dose arms. Both weekly dose levels were evaluated as add-on therapy against dose-matched placebo during the same treatment period.

REIMAGINE 3 was a double-blind, parallel-group, randomized, controlled, phase 3a study conducted at 46 centres in the USA, China, Japan, Serbia, Slovakia, and South Africa. Eligible participants were adults with type 2 diabetes, HbA1c 7.0% to 10.5%, and stable once-daily basal insulin with or without metformin. Investigators screened 340 people and randomly assigned 274, and mean baseline HbA1c was 8.8%. Baseline sex distribution was 58% male and 42% female, and participants entered a 2:2:1:1 randomization to weekly subcutaneous cagrilintide-semaglutide 2.4 mg each, 1.0 mg each, or dose-matched placebo. Treatment lasted 40 weeks, active injections were visually identical to placebo, and the primary endpoint was mean week-40 HbA1c change; secondary endpoints included bodyweight and safety including hypoglycaemia.

In the week 40 HbA1c results, mean changes were -2.33% in the 2.4 mg group, -2.10% in the 1.0 mg group, and -0.66% with placebo. Group sizes were n=90, n=93, and n=91, respectively, for the higher-dose, lower-dose, and pooled placebo groups at randomisation. Estimated treatment differences versus placebo were -1.68 percentage points for 2.4 mg and -1.44 percentage points for 1.0 mg. The corresponding 95% confidence intervals were -1.95 to -1.41 and -1.71 to -1.17, and both comparisons had p<0.0001. Active treatment was also associated with bodyweight reductions of 10% to 12%, and both dose levels met the primary endpoint.

Adverse events occurred in 72 of 90 participants (80%) in the 2.4 mg group, 66 of 93 (71%) in the 1.0 mg group, and 65 of 91 (71%) with placebo. They were mostly mild or moderate gastrointestinal disorders. No severe hypoglycaemia was reported, and one death occurred in the 1.0 mg group and was considered unrelated to treatment because of malignancy. Overall, cagrilintide-semaglutide added to basal insulin was associated with greater week-40 HbA1c and bodyweight reductions than placebo, with safety findings reported mainly as gastrointestinal events in this population.