Novo Nordisk's cagrilintide and semaglutide combination CagriSema delivered superior weight loss versus a lower dose of tirzepatide in type 2 diabetes and met its primary obesity endpoint against placebo, providing Novo with positive data as it awaits a US regulatory decision on the drug's obesity indication expected in Q4 2026.
CagriSema combines cagrilintide, a long-acting amylin analogue with activity at amylin and calcitonin receptors, with semaglutide, a GLP-1 receptor agonist, targeting complementary pathways involved in appetite regulation and energy intake.
In the Phase III REIMAGINE 5 trial, CagriSema 1.0 mg/1.0 mg achieved estimated average weight loss of 12.4% versus 9.1% for tirzepatide 5 mg at week 60 in adults with type 2 diabetes inadequately controlled on metformin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, or both — meeting the primary superiority endpoint on weight. HbA1c reduction was 1.71% versus 1.67%, meeting the non-inferiority co-primary endpoint. In the separate Phase III REDEFINE 9 obesity trial, CagriSema 1.0 mg/1.0 mg produced 21.0% weight loss versus 2.0% for placebo at week 68, with the primary superiority endpoint met. Novo reported improvements versus placebo across prespecified supportive endpoints including systolic blood pressure, waist-to-height ratio, and fasting lipid profile, though numerical values for these were not disclosed. Both trials, Novo said, showed a safety profile consistent with previous studies.
The REIMAGINE 5 comparison is against tirzepatide's 5 mg dose — not the 15 mg dose used in the pivotal REDEFINE 4 obesity head-to-head, where CagriSema 2.4 mg/2.4 mg failed to demonstrate non-inferiority, achieving 23.0% weight loss versus 25.5% for tirzepatide 15 mg. Novo's Q2 2026 earnings call also disclosed that in REIMAGINE 4, CagriSema 2.4 mg/2.4 mg was non-inferior to tirzepatide 15 mg on weight but failed the HbA1c non-inferiority co-primary endpoint. The REIMAGINE 5 win at the 1.0 mg/1.0 mg dose versus tirzepatide 5 mg is therefore a distinct competitive scenario, relevant to patients who do not escalate to or tolerate maximum doses of either drug. Novo framed the results as evidence for dose flexibility in individualized care.