Research Brief

Retatrutide: Safety Profile & Research Summary

17 Citacoes PubMedRevisado por EspecialistasCertificado GMPUltima Revisao: julho de 2026

Preclinical & Clinical Research Summary

Key Preclinical (Animal) Studies

Estudo	Modelo	Principais Achados	Ref
Coskun et al. (2022) Cell Metabolism	DIO C57/Bl6 mice; 10 nmol/kg daily SC	36.9% peso corporal loss (vs. 21.2% tirzepatide); 86.8% massa gorda reduction; melhorou glicose sanguinea, insulin, ALT, liver triglycerides; engages all three receptors in vivo	[4]
Urva et al. (2023) Diabetes Obes. Metab.	C57/Bl6 camundongos obesos; 10 nmol/kg SC	Dose-dependent gastric emptying delay; cronico(a) treatment atenuou GI slowing (tachyphylaxis); superior weight/food intake reduction vs. semaglutide alone	[17]
Ma et al. (2025) Endocrine	Diabetic db/db mice; 10 nmol/kg daily SC, 10 weeks	Superior efficacy over liraglutide and tirzepatide in reducing ALT, AST, cholesterol, triglycerides, LDL; mitigou inflammatory and fibrotic processes in diabetic kidney	[15]
Marathe et al. (2025) NPJ Metab. Health Dis.	Pancreatic and lung cancer models in camundongos obesos	Reduced tumor engraftment; retardou tumor onset; greater tumor supressao do que semaglutide; durable antitumor effects apesar de partial weight regain	[14]

Key Clinical (Human) Studies

Estudo	Population / Design	Key Results	Ref
Urva et al. (2022) Lancet (Phase 1b)	T2D subjects; MAD, 0.5–12 mg SC weekly; RCT	Dose-dependent HbA1c and reducao de pesos; t_1/2 ~6 days confirmou; GI AEs dose-related; bem tolerado(a) overall	[8]
Jastreboff et al. (2023) NEJM (Phase 2)	Adults with obesidade (no T2D); 1, 4, 8, 12 mg SC weekly; 48 wks; RCT	-24.2% mean perda de peso (12 mg); dose-dependente; not plateaued at 48 wks; GI AEs a maioria common	[1]
Rosenstock et al. (2023) Lancet (Phase 2)	Adults with T2D; 0.5–12 mg SC weekly; 36 wks; RCT	HbA1c -2.02% (12 mg); significant perda de peso; melhorou sensibilidade a insulina; bem tolerado(a)	[2]
Sanyal et al. (2024) Nature Med. (Phase 2a)	MASLD substudy; MRI-PDFF assessed liver fat; 48 wks	>85% alcancou liver fat normalization (<5%) at 8–12 mg doses; up to 86% relative liver fat reduction	[3]
TRIUMPH-4 (Phase 3, 2025) Eli Lilly Press Release	Obesity + knee OA; 9 & 12 mg SC weekly; 68 wks	Up to 28.7% mean perda de peso; WOMAC pain scores melhorou by up to 75.8%; primeiro(a) successful Phase 3 trial	[5]

Safety Profile Summary

Category	Detail	Incidence / Notes
Common GI AEs	Nausea, diarrhea, vomiting, constipation, diminuiu appetite	Nausea up to 63% at highest doses; dose-dependente; a maioria common during titration[12][13]
Skin Hyperesthesia	Increased skin sensitivity, dysesthesia, "skin pain"	Up to 7% (vs. 1% placebo) in Phase 2[10]
Heart Rate	Dose-dependent increase, peaking at 24 weeks before declining	Mild to moderate arrhythmias relatado(a)[10]
Serious AEs	Acute pancreatitis (single cases); gallbladder disease; hipotensao	SAE rate semelhante a placebo (~4–5%)[12]
Hepatic Safety	No hepatotoxicity signals; transient ALT/AST elevations resolved	Monitored in all trials[12]

Dosage Summary

Setting	Dose	Route / Schedule	Notes
In Vitro (EC50)	0.0643 nM (GIPR), 0.775 nM (GLP-1R), 5.79 nM (GCGR)	Cell culture	Biased toward GIP potency[4]
Animal (Mice)	10 nmol/kg daily	SC injection	Standard efficacy dosing; t_1/2 21 h in mice[4]
Phase 1 (SAD)	0.1–6 mg (dose unica)	SC injection	Safety/PK assessment[8]
Phase 2 (Maintenance)	1, 4, 8, 12 mg	SC once weekly; titrated from 2 or 4 mg	Titration by 2–4 mg every 4 weeks[1][2]
Phase 3 (TRIUMPH)	Target doses: 9 mg and 12 mg	SC once weekly; iniciou at 2 mg	Ongoing registrational trials[5]

Pharmacokinetic Profile

Parametro	Valor	Notes
Half-life (Human)	~6 days	Supports once-dosagem semanal[8]
Half-life (Mouse)	~21 hours	Single 47 μg/kg dose[4]
T_max	12–72 hours	Post-SC dose in humans
Metabolism	Hepatic proteolise; fatty acid β-oxidation	No CYP450 interaction
Clearance (Mouse)	11.22 mL/h/kg	CD-1 mice

&x26A0;️ Important Disclaimer

This product is sold strictly for in-vitro research and laboratory use only. It nao e aprovado(a) por the FDA for human consumption, medical use, diagnostic use, or veterinary use. Bodily introduction of qualquer kind into humans or animals is strictly forbidden by law. All products are supplied as research chemicals only. The information provided here is compiled from revisado(a) por pares scientific literature e e intended solely for educational and informational purposes.

About This Research Profile

This research profile was compiled from revisado(a) por pares sources incluindo publications no(a) New England Journal of Medicine, The Lancet, Nature Medicine, Cell Metabolism, e outros(as) high-impact journals. All citations reference publicly available scientific literature. The profile is regularly reviewed and updated to reflect the latest research findings. Last reviewed: February 2026.

Aviso sobre Estudos In Vitro / Pré-clínicos: Os achados de pesquisa descritos acima foram observados em estudos laboratoriais (in vitro) e/ou em modelos animais. Esses resultados podem não se traduzir em desfechos humanos. Nenhuma alegação é feita em relação a aplicações terapêuticas humanas.

Apenas para Uso Educacional: Este conteúdo é fornecido apenas para fins informativos e educacionais. Não se destina a ser aconselhamento médico e não deve ser utilizado para diagnosticar, tratar, curar ou prevenir qualquer doença ou condição médica. Sempre consulte profissionais de saúde qualificados para decisões médicas.

Referencias

Perguntas de Pesquisa Relacionadas

→ What Is Retatrutide?→ Retatrutide: Mechanism of Action → Retatrutide: Research Applications → Retatrutide: Chemical Properties → Storing Retatrutide: Best Practices

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