Retatrutide

Retatrutide is a novel triple agonist peptide of the glucagon receptor (GCGR), glucose-dependent insulinotropic polypeptide receptor (GIPR) and glucagon-like peptide-1 receptor (GLP-1R). Retatrutide inhibits human GCGR, GIPR and GLP-1R with EC50 values of 5.79, 0.0643 and 0.775 nM, respectively and mouse GCGR, GIPR, and GLP-1R with EC50 values of 2.32, 0.191 and 0.794 nM, respectively. It is an important tool for obesity research.
Retatrutide potently activates the GLP-1R signaling pathway to stimulate glucose-dependent insulin secretion through activity at the GIP receptor (GIPR) or the GLP-1R.
Retatrutide is a synthetic peptide with glucose-lowering effects. It is an antidiabetic agent against type 2 diabetes (T2D), stimulating insulin and suppressing glucagon secretion in a glucose-dependent manner.
Retatrutide was also shown to delay gastric emptying, lower fasting and postprandial glucose concentration, decrease food intake and reduce body weight in patients with type 2 diabetes.

When injected into mice suffering from diabetes-induced kidney injury, retatrutide was found to markedly reduce albuminuria levels while also increasing renal filtration rate. This was attributed to its ability to activate GLP-1R/GR-dependent signalling pathways, which then produced anti-inflammatory and antiapoptotic effects that protected the kidneys from further damage. Additionally, it has been shown to directly modulate glomerular permeability, thus leading to improved urinary concentration. Initial results indicate that the peptide can induce marked improvements in albuminuria levels within just four weeks of treatment when compared to other treatments for chronic kidney disease such as ACE inhibitors or angiotensin receptor blockers (ARBs). Moreover, retatrutide has demonstrated a greater effect than either ACE inhibitors or ARBs at reducing systolic blood pressure without inducing significant side effects.

The most common side effects of retatrutide are gastrointestinal, including: Nausea, Diarrhea, Vomiting, and Constipation. At higher doses, researchers stated these symptoms were "mostly mild to moderate in severity" and typically treated by lowering the dosage. However, 7% of patients also experienced skin tingling. At 24 weeks of treatment, patients' heart rates on higher doses peaked but declined afterward.

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