Slentrol
Evidence Grade D — Primarily preclinical. 18 published studies, mostly animal models. 0 registered clinical trials.
Dirlotapide (Slentrol) is a small molecule drug — not a peptide — approved exclusively for obese dogs. It has no approval for human use. It is included in this database because its mechanism (blocking fat absorption) connects to peptide hormone signalling cascades that control appetite. It was the first drug ever approved specifically for canine obesity.
18 published studies: 3 human, 13 animal, 3 in-vitro, 2 reviews
Dirlotapide is approved exclusively for veterinary use in obese dogs. It has no approval for human use. Pivotal canine trials (245 dogs) showed 14–16% weight loss. Weight rebounded after treatment cessation without dietary management.
Dirlotapide is not a peptide and is not approved for human use. Its inclusion reflects the broader metabolic pathway context. The compound's mechanism illustrates how gut fat sensing triggers peptide hormone responses that suppress appetite.
Dirlotapide blocks the enzyme (MTP) that assembles dietary fat into transport particles in the gut lining. This prevents fat absorption and, through peptide hormone signalling cascades (PYY, GLP-1), also triggers appetite suppression. Approximately 90% of the weight loss effect in dogs comes from reduced food intake rather than fat malabsorption directly.
Research suggests trials in dogs (245 animals) showed 14-16% weight loss, with approximately 90% of the effect coming from reduced food intake rather than direct fat malabsorption. Weight rebounded after treatment stopped unless dietary management was maintained. No human development was pursued because a related compound tested in humans caused liver enzyme elevations. The compound illustrates how gut fat sensing triggers peptide hormone responses (PYY, GLP-1) that suppress appetite — a concept that connects to the broader metabolic peptide field.
No trials registered on ClinicalTrials.gov for this compound.
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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.
