Novo Nordisk Launches AMAZE Phase 3 Program for Zenagamtide

Novo Nordisk's investigational dual GLP-1/amylin agonist zenagamtide is being evaluated in subcutaneous injectable trials.

To expand options for chronic weight management, Novo Nordisk has formally launched its Phase 3 clinical trial program, named AMAZE, to evaluate the investigational drug zenagamtide. Zenagamtide (previously known in early development as amycretin) represents a new class of treatments designed for metabolic health. The drug is a unimolecular dual-agonist, which means it simultaneously activates two distinct hormone receptor pathways in the body: the GLP-1 receptor and the amylin receptor.

Amylin is a hormone naturally co-secreted with insulin by the pancreas in response to eating, playing a critical role in appetite control and satiety. While existing therapies focus primarily on the GLP-1 pathway, zenagamtide combines both mechanisms to deliver a more comprehensive signal to the brain. This late-stage trial program represents a significant shift from single-target therapies toward multi-receptor agonists that engage multiple physiological systems at once.

Understanding Zenagamtide: A Dual GLP-1 and Amylin Receptor Agonist

Zenagamtide's dual-agonist mechanism sets it apart from current weight loss options by combining the benefits of two distinct fullness hormones. GLP-1 agonists work by slowing digestion, helping release insulin, and telling the brain you are full. Amylin works through separate pathways in the brain stem to slow stomach emptying and promote satiety. Combining them is designed to regulate energy intake more effectively than single-target drugs.

Developing a unimolecular agonist represents a major chemical advancement, as it allows a single peptide to target both receptors in a coordinated manner. Historically, combining multiple hormone therapies required separate injections or complex formulations. Furthermore, while GLP-1 treatments can cause loss of both fat and muscle, early data suggest that amylin pathways may help preserve lean muscle mass during weight loss, supporting better body composition.

The Structure and Scope of the AMAZE Phase 3 Clinical Program

The AMAZE clinical program is a comprehensive series of Phase 3 trials designed to establish the safety and efficacy of weekly subcutaneous zenagamtide. The studies will evaluate the drug across diverse patient cohorts, addressing a wide range of obesity-related health complications. The trial program's broad scope highlights the multi-faceted health benefits of effective weight care.

Specifically, the AMAZE 1 and AMAZE 2 studies are pivotal Phase 3a trials. AMAZE 1 will evaluate the efficacy and safety of zenagamtide in adults with obesity or overweight who do not have type 2 diabetes. AMAZE 2 will test the same parameters in adults who have both obesity and type 2 diabetes, providing key data on blood sugar control and weight reduction. Additional trials will evaluate the drug in patients with specific comorbidities:

• AMAZE 3 and AMAZE 4 will test zenagamtide in patients with obesity and moderate-to-severe obstructive sleep apnea.
• AMAZE 5 and AMAZE 6 will evaluate the drug's impact on patients with obesity and knee osteoarthritis, where reducing joint load is a key part of treatment.

Evaluating AMAZE 8: Head-to-Head Comparison with Semaglutide

Among the trials in the program, the AMAZE 8 trial (NCT07400107) is highly anticipated by clinicians. This randomized, double-blind, active-controlled study will compare weekly subcutaneous zenagamtide directly against weekly semaglutide. Comparing the drug against semaglutide is a rigorous benchmark, as semaglutide is the current gold standard in many commercial semaglutide treatment programs.

The primary goal of AMAZE 8 is to show if the dual-action mechanism of zenagamtide achieves superior weight reduction and blood sugar control compared to semaglutide monotherapy. Researchers will measure the percentage change in body weight and reductions in A1c levels over the treatment period. Secondary objectives include tracking cardiovascular risk markers, cholesterol profiles, and patient quality-of-life improvements.

Prior Clinical Findings and Efficacy Profiles of Zenagamtide

The launch of the AMAZE program is supported by positive data from Phase 1 and Phase 2 studies. Early-stage trials evaluating both oral and subcutaneous formulations of zenagamtide showed significant, dose-dependent weight reduction. The clinical data suggests that the drug has strong potential for weight care.

In Phase 1 trials of the oral formulation, which uses SNAC technology to survive stomach acid, participants achieved an average 13.1% weight loss after 12 weeks of treatment at optimal doses. Subcutaneous injections of zenagamtide produced even higher weight loss, with some cohorts experiencing up to 22% weight reduction over 36 weeks. While these early results are promising, the larger Phase 3 trials are necessary to confirm safety and efficacy across diverse real-world populations.

Future Directions, Regulatory Pathways, and Market Dynamics

While the AMAZE program is a major step forward, regulatory approval and commercial availability are still several years away. The Phase 3 trials must collect long-term safety data before the developer can submit applications to the FDA. Consequently, zenagamtide is currently an investigational drug and is not available for prescription.

In the meantime, patients can explore existing treatments for weight management. For example, those looking for active care can review current tirzepatide options and other approved options. To begin, you can check if you qualify online and view current pricing for metabolic wellness programs. Consulting a qualified healthcare provider remains the safest way to find the right treatment option for your needs.

This article is for informational purposes only and is not medical advice. Consult your healthcare provider before starting any weight loss medication or treatment.