Retatrutide

0

200-001-8

White lyophilized

Soluble in water (5mg/ml).

-20°C

-20°C

Investigated for the treatment of type 2 diabetes mellitus (T2DM), obesity, and overweight in adults. Additional potential indications under clinical evaluation include non-alcoholic fatty liver disease (NAFLD), metabolic dysfunction-associated steatohepatitis (MASH), and cardiovascular risk reduction.

No significant hepatotoxicity has been reported in clinical trials to date. However, periodic monitoring of liver enzymes (ALT, AST) is recommended, especially in patients with pre-existing liver conditions or during long-term therapy.

Triple agonist of GLP-1, GIP, and GLP-2 receptors; peptide-based antidiabetic and anti-obesity agent.

Subcutaneously administered; metabolized via enzymatic degradation in liver and kidneys; eliminated renally and fecally.

Glycemic control in type 2 diabetes and chronic weight management in obesity or overweight with comorbidities.

Risk of GI adverse effects, hypoglycemia (with insulin/sulfonylureas), pancreatitis, gallbladder disease, and acute kidney injury; contraindicated in personal/family history of MTC or MEN 2; not for use in pregnancy.

Human lethal dose not established; preclinical data suggest a wide safety margin.

Generally well tolerated; most adverse events are mild-to-moderate gastrointestinal symptoms that improve over time.

Long-acting triple receptor agonist that enhances insulin secretion, suppresses glucagon, delays gastric emptying, promotes satiety, and may support gut integrity via GLP-2 activity.

GLP-1 Receptor Agonists; GIP Receptor Agonists; Peptide Hormones; Hypoglycemic Agents; Anti-Obesity Agents

Slow SC absorption (Tmax ～4–6 h); high plasma protein binding (～95%); primarily degraded by peptidases; excreted in urine and feces; half-life ～3.5 days enabling once-weekly dosing.

Inactive or low-activity peptide fragments generated by proteolytic cleavage, not dependent on CYP450 enzymes.

Approximately 3.5 days.

Retatrutide is a triple agonist of GLP-1, GIP, and GLP-2 receptors, promoting insulin secretion, suppressing glucagon release, delaying gastric emptying, enhancing satiety, and protecting renal function by reducing albuminuria in diabetic kidney disease models.

No significant impurities reported in clinical-grade formulations; minor peptide degradation products may occur during storage but are within acceptable limits per ICH guidelines.

Common side effects include nausea, diarrhea, vomiting, constipation, and headache; rare but serious risks include pancreatitis, gallbladder disease, hypoglycemia, and acute kidney injury.

In case of overdose or severe adverse reaction, discontinue drug immediately; provide supportive care including hydration, antiemetics, and monitoring of vital signs; no specific antidote available.

No known antidote; management is symptomatic and supportive; monitor for dehydration, electrolyte imbalance, and hypoglycemia; hospitalization may be required in severe cases.

Retatrutide has favorable safety profile in clinical trials with dose-dependent GI tolerability; no major organ toxicities observed; long-term human toxicity data still under evaluation.

Retatrutide; Glucagon-Like Peptide-1 Receptor Agonists; Obesity; Diabetes Mellitus, Type 2; Weight Loss Agents; Peptide Hormones

Not listed as a controlled substance under the U.S. Controlled Substances Act (DEA); not scheduled by FDA or international regulatory bodies.

Subcutaneous injection only; systemic absorption via SC route; not intended for oral, intravenous, or other routes of administration.

Nausea, vomiting, diarrhea, constipation, headache, fatigue, dizziness, abdominal pain, and hypoglycemia-related symptoms such as sweating, tremor, and confusion.

Pancreas, liver, gastrointestinal tract, kidneys, adipose tissue, central nervous system (via appetite regulation), and cardiovascular system.