Zenagamtide, NN9487
Evidence Grade D — Primarily preclinical. 14 published studies, mostly animal models. 1 registered clinical trial.
Amycretin is a single molecule from Novo Nordisk that activates both GLP-1 and amylin receptors at once — achieving what CagriSema does with two separate drugs, but from one molecule. An oral tablet formulation has shown strikingly fast weight loss in early trials: 13% in just 12 weeks. The injectable version achieved 24% weight loss at 36 weeks.
14 published studies: 7 human, 0 animal, 0 in-vitro, 9 reviews
Amycretin is in early-phase development (not yet approved). The oral formulation achieved 13.1% weight loss at just 12 weeks — substantially faster than existing oral options. The subcutaneous formulation achieved 24.3% at 36 weeks. Both results are from Phase I/II trials with relatively small patient numbers.
Amycretin's significance lies in its oral formulation achieving weight loss approaching injectable drugs. If the early results are confirmed in larger trials, an effective oral dual-agonist could significantly expand the obesity treatment population. Phase III trials are anticipated.
Amycretin combines GLP-1 and amylin receptor agonism within a single 68-amino-acid peptide. The molecule uses a calcitonin-based amylin sequence rather than native amylin, which was necessary because native amylin sequences lost potency when fused to GLP-1 analogues. This design achieves the same dual-pathway approach as CagriSema but from a single molecular entity.
Early-phase results are highly promising but based on relatively small patient numbers (125-448 per study). The oral formulation's 13.1% weight loss at 12 weeks is substantially faster than any existing oral option, approaching results typically seen only with injectables. The subcutaneous formulation's 24.3% at 36 weeks is among the highest reported for any obesity compound. Phase III trials for both oral and injectable formulations are planned for early 2026. Key uncertainties include whether the impressive early trajectory will translate proportionally in larger populations and longer treatment durations. Gastrointestinal side effects are consistent with the GLP-1 class. If the oral formulation confirms its early promise, an effective oral dual-agonist pill could significantly expand the obesity treatment population.
A Research Study of How a New Medicine Called Amycretin, Given as Tablets, Works in Japanese Men With Obesity
The information on this page is provided for educational and research reference purposes only. This is not medical advice. Always consult a qualified healthcare professional before making any health-related decisions.
Liraglutide is marketed as Victoza for type 2 diabetes (approved 2010) and Saxenda for weight management (approved 2014). The LEADER trial, involving over 9,300 patients followed for nearly four years, established that liraglutide reduced the risk of major cardiovascular events by 13% — a landmark finding that helped establish GLP-1 treatments as a class with heart benefits. Saxenda is also approved for adolescents aged 12 and older. While historically significant, liraglutide has been substantially surpassed by newer agents. In a direct comparison, semaglutide achieved 15.8% weight loss compared to liraglutide's 6.4%. Liraglutide remains relevant as a lower-intensity option and as a benchmark against which newer treatments are measured. It has over a decade of real-world safety data, making it one of the best-understood medications in this class.
Setmelanotide is marketed as Imcivree (Rhythm Pharmaceuticals; approved November 2020 for POMC, PCSK1, or LEPR deficiency; June 2022 for Bardet-Biedl syndrome; December 2024 expanded to patients aged 2 years and older). Genetic testing confirming an eligible mutation is required before treatment. In patients with POMC or PCSK1 deficiency, approximately 80% achieved at least 10% weight loss in clinical trials. In Bardet-Biedl syndrome, 32.3% achieved the same threshold. The most common side effects are injection-site reactions and skin darkening (due to the melanocortin pathway's connection to pigmentation). Setmelanotide exemplifies precision medicine — it is highly effective in the specific genetic populations it targets but is not indicated for common obesity.
HGH Fragment 176-191 has no marketing authorisation. A Phase IIa trial in obesity (approximately 300 patients) failed to demonstrate statistically significant weight loss at any dose tested. The clinical development programme was discontinued. The disconnect between animal data (which showed significant fat reduction in obese mice) and the failed human trial is the defining feature of this compound's development history. Products available through unregulated channels lack pharmaceutical quality assurance. The failed Phase II trial represents the highest level of clinical evidence available.
