AM833, NN0174
Evidence Grade C — Moderate human evidence. 71 published studies, 42 human. 36 registered clinical trials.
Cagrilintide is a long-acting amylin analogue from Novo Nordisk — targeting a different satiety pathway than GLP-1 drugs like semaglutide. While it produces meaningful weight loss on its own (about 12%), its primary strategic value is as the amylin component of CagriSema, a combination with semaglutide designed to achieve greater weight loss than either drug alone.
71 published studies: 42 human, 3 animal, 5 in-vitro, 36 reviews
Cagrilintide is in Phase III development (not yet approved). In a Phase II trial (706 patients), cagrilintide 4.5 mg achieved 10.8% weight loss, outperforming the active comparator liraglutide 3.0 mg (9.0%). Phase III results (REDEFINE-1) showed 11.8% weight loss as monotherapy.
Cagrilintide's primary strategic significance is as the amylin component of CagriSema (#162). As a standalone agent, its weight loss is less than currently available GLP-1 agonists like semaglutide. Its value lies in the complementary mechanism that produces additive effects when combined with semaglutide.
Cagrilintide activates amylin receptors in the brain, promoting satiety through a pathway that is complementary to but distinct from GLP-1. While GLP-1 drugs primarily affect appetite and gastric emptying, amylin signalling acts on both the homeostatic (energy balance) and hedonic (reward-based) feeding centres. This dual-centre suppression of food intake may explain the additive weight loss observed when amylin is combined with GLP-1 agonists.
In a Phase II trial of 706 patients, the highest dose of cagrilintide achieved 10.8% weight loss, outperforming the active comparator liraglutide (9.0%). Phase III monotherapy results (REDEFINE-1) showed 11.8% weight loss — meaningful but less than currently available GLP-1 treatments like semaglutide. Cagrilintide's true potential lies in combination. By targeting the amylin pathway alongside GLP-1, it adds a complementary mechanism that amplifies weight loss beyond what either pathway achieves alone. The Phase III monotherapy programme (RENEW) was initiated in late 2025. Injection-site reactions occur in about 17% of patients. No regulatory filing for cagrilintide as a standalone treatment has been made, and approval is unlikely before 2028.
A Research Study to Compare Two Different Versions of Injectable CagriSema in People With Type 2 Diabetes
A Research Study to See How Much CagriSema Lowers Blood Sugar and Body Weight Compared to Placebo in Children and Adolescents With Type 2 Diabetes
A Research Study to Compare Different Versions of Injectable CagriSema and Placebo in People With Excess Body Weight
A Study Looking at How Weekly Injections of Two Hormones - GIP and Amylin - Affect Stomach-related Side Effects in People Who Are Overweight or Obese
A Research Study on How Well Cagrilintide and CagriSema Work in Children and Adolescents With Excess Body Weight
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.
