Novo Nordisk Counters Lilly at ADA 2026: Zenagamtide (Amycretin) Hits 14.6% Weight Loss and CagriSema Phase 3 Diabetes Trials Succeed
At the American Diabetes Association (ADA) 2026 Scientific Sessions in New Orleans (June 5–8, 2026), Novo Nordisk presented powerful clinical data across its next-generation cardiometabolic pipeline. The dual announcements of positive Phase 2 data for zenagamtide (the international nonproprietary name for amycretin) and comprehensive Phase 3 results for its CagriSema development program (REIMAGINE 1, 2, and 3) represent Novo's strategic response to Eli Lilly's dominant clinical showing with retatrutide.
Both zenagamtide and CagriSema highlight Novo Nordisk's pivot toward targeting the amylin pathway alongside GLP-1, aiming to achieve deeper metabolic control and superior weight loss.
1. Zenagamtide (Amycretin) Phase 2 Breakthrough in Type 2 Diabetes
Zenagamtide is a first-in-class, unimolecular peptide co-agonist that activates both GLP-1 and amylin receptors. It is under clinical development in both subcutaneous and oral formulations.
- Efficacy: In a 36-week, randomized, double-blind, Phase 2 trial of 262 adults with Type 2 diabetes (T2D), subcutaneous zenagamtide met its primary endpoint across all six investigated doses (0.4 mg to 40 mg).
- Glycemic Control: From a baseline A1C of 7.8%, the highest dose of 40 mg achieved an A1C reduction of -1.71%. Up to 89.1% of participants reached an A1C below 7.0%, and 76.2% reached ≤6.5%. Time in range (70–180 mg/dL) reached up to 91.5%.
- Weight Loss: As a secondary endpoint, zenagamtide 40 mg delivered a massive 14.6% (mean baseline weight ~219 lbs) body weight reduction at week 36, with weight loss still progressing.
- Titration & Next Steps: The trial used a rigid, fixed-dose-escalation design, meaning patients who couldn't tolerate dose jumps were discontinued. Despite this, safety was consistent with existing incretins (primarily mild-to-moderate GI events). Novo Nordisk plans to initiate a global Phase 3 program for zenagamtide in T2D in the second half of 2026.
2. CagriSema Phase 3 REIMAGINE Program Succeeds in Type 2 Diabetes
CagriSema is a fixed-dose, once-weekly combination of the amylin analog cagrilintide (2.4 mg) and the GLP-1 receptor agonist semaglutide (2.4 mg). At ADA 2026, Novo unveiled data from three Phase 3 trials in its REIMAGINE program for adults with T2D:
- REIMAGINE 1 (Diet & Exercise Failures): Over 40 weeks, CagriSema 2.4 mg/2.4 mg reduced A1C by -1.8% (from a 7.8% baseline) and reduced body weight by -13.8% vs. -0.1% and -1.4% for placebo, respectively.
- REIMAGINE 2 (Metformin +/- SGLT2i Failures): In a massive 2,713-patient, 68-week trial, CagriSema 2.4 mg/2.4 mg achieved a -1.91% A1C reduction and -14.2% weight loss, significantly outperforming high-dose semaglutide 2.4 mg alone (-1.75% A1C; -10.2% weight loss).
- REIMAGINE 3 (Add-on to Basal Insulin): Over 40 weeks, CagriSema achieved a -2.33% A1C reduction and -12.0% weight loss vs. -0.66% and +1.1% for placebo.
- Regulatory Status: Novo Nordisk has submitted a New Drug Application (NDA) to the FDA for CagriSema for weight management, with an approval decision expected in Q4 2026.
Verbatim Quotes and Context
- Martin Holst Lange, Chief Scientific Officer and Executive Vice President of R&D at Novo Nordisk, on zenagamtide's dual mechanism:
"Zenagamtide is the first investigational treatment for type 2 diabetes to combine GLP-1 and amylin receptor agonist mechanisms of action in a single molecule. These phase 2 results build on the growing body of evidence which demonstrates the potential of zenagamtide to meaningfully impact blood glucose control in patients with type 2 diabetes and also body weight..."
- From the REIMAGINE 2 trial data comparing CagriSema to semaglutide alone:
"The study met its primary endpoint of change in A1C across all doses and also key supportive secondary endpoint of change in body weight... CagriSema 2.4 mg/2.4 mg achieved a -1.91% A1C reduction and -14.2% weight loss vs. semaglutide 2.4 mg (-1.75% and -10.2%)."
What This Means for Investors
- The Amylin Era Has Arrived: Novo Nordisk is aggressively positioning amylin co-activation as the key to unlocking weight loss and glycemic control that rivals Lilly's GIP/GLP-1/glucagon (retatrutide) platform.
- Zenagamtide vs. CagriSema: While CagriSema is a co-formulation of two separate peptides nearing FDA approval (Q4 2026), zenagamtide is a single, elegant unimolecular peptide that represents Novo's long-term future. Zenagamtide's 14.6% weight loss at 36 weeks in diabetes patients is exceptional, as diabetes patients typically lose weight much more slowly than non-diabetics.
- Key Catalyst to Watch: Investors must watch for the FDA's regulatory decision on CagriSema in Q4 2026, which will mark the commercial debut of the first GLP-1/amylin combination therapy.