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.

Retatrutide (LY3437943), a single peptide conjugated to a lipid diacid molecule, exerts a powerful agonist effect on the human glucagon‐receptor (GCGR), GIPR, and GLP‐1R. In comparison with the human glucagon and glucagon‐like peptide 1 (GLP‐1), retatrutide exhibits reduced potency (by a factor of 0.3 and 0.4, respectively) on the GCGR and GLP‐1R while displaying enhanced potency at the human GIPR (by a factor of 8.9) when compared to the glucose‐dependent insulinotropic polypeptide (GIP)[7].

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.