Novo Nordisk Unveils Phase 3 CagriSema and Phase 2 Zenagamtide Data at ADA 2026

Novo Nordisk Unveils Phase 3 CagriSema and Phase 2 Zenagamtide Data at ADA 2026

At the American Diabetes Association (ADA) 2026 Scientific Sessions, Novo Nordisk A/S showcased key data from its dual-acting metabolic pipeline, reinforcing its focus on combination and multi-receptor mechanisms to counter Eli Lilly's high-potency assets.

CagriSema Outperforms Semaglutide in Phase 3 REIMAGINE 2 Trial

Novo Nordisk presented the detailed results of its Phase 3 REIMAGINE 2 trial evaluating CagriSema—a weekly subcutaneous fixed-dose combination of its GLP-1 receptor agonist semaglutide and its long-acting amylin analog cagrilintide.

The 68-week trial evaluated 2,728 adults with type 2 diabetes inadequately controlled on metformin (with or without an SGLT2 inhibitor) across multiple dosing arms. The trial established CagriSema's clinical superiority in both glycemic control and weight loss over its individual components¹:

• Glycemic Control: Under the efficacy estimand, patients treated with CagriSema 2.4 mg/2.4 mg achieved a mean 1.91% HbA1c reduction from a baseline of 8.2%, compared to a 1.76% reduction with semaglutide 2.4 mg alone.
• Weight Loss: From a baseline body weight of 101 kg (~222 lbs), CagriSema patients achieved a mean 14.2% body weight reduction, compared to 10.2% with semaglutide 2.4 mg.
• Under the high dose, 43% of CagriSema patients achieved a weight loss of 15% or greater, and 24% achieved 20% or greater. No weight loss plateau was observed at week 68.
• Tolerability: CagriSema exhibited a safe and well-tolerated profile, with mild-to-moderate gastrointestinal adverse events consistent with the incretin and amylin classes.

While CagriSema failed to demonstrate non-inferiority to Lilly's Zepbound in its separate REDEFINE-4 obesity trial in February 2026 (losing 23% vs Zepbound's 25.5% weight loss), Novo remains highly confident in its dual-mechanism profile. The company submitted CagriSema for weight management to the FDA in December 2025 and expects to discuss regulatory pathways for diabetes based on the REIMAGINE program.

Zenagamtide (Amycretin) Demonstrates Strong Phase 2 Efficacy

Novo Nordisk also presented positive Phase 2 dose-finding results for zenagamtide (formerly known as amycretin), its first-in-class unimolecular peptide agonist targeting both GLP-1 and amylin receptors.

The 36-week trial randomized 262 adults with type 2 diabetes across six subcutaneous doses (0.4 mg to 40 mg) versus a pooled placebo:

• A1C Reduction: From a baseline of 7.8%, the highest dose of zenagamtide (40 mg once-weekly) led to a mean 1.71% HbA1c reduction (estimated treatment difference vs placebo of -1.56%). Up to 89.1% of participants achieved an A1C level below 7.0%.
• Weight Loss: Participants on the 40 mg dose achieved a mean 14.6% body weight reduction from a baseline of 99.2 kg (~219 lbs), compared to just 2.1% in the placebo group.
• Time in Range: Patients on zenagamtide 40 mg spent an average of 91.5% of their day within the target glucose range of 70–180 mg/dL.

These strong results support the advancement of zenagamtide into late-stage trials. Novo Nordisk is planning to initiate the zenagamtide Phase 3 development program for type 2 diabetes in the second half of 2026.