Design of new frog-based molecules that activate both GLP-1 and glucagon receptors

A novel peptide, xGLP/GCG-15, shows significant hypoglycemic effects and body weight loss in rodent models.

• xGLP/GCG-15 is engineered from selective GLP-1R agonist xGLP-1, incorporating structural elements from oxyntomodulin, glucagon, and exendin-4.
• Modifications with fatty acid resulted in a metabolically stable peptide with enhanced dual activity at GLP-1R and GCGR.
• Chronic administration of xGLP/GCG-15 in db/db and diet-induced obesity rodent models led to improved glucose tolerance and normalized lipid metabolism.
• The peptide significantly reduced adiposity and liver steatosis in relevant rodent models.
• xGLP/GCG-15's effects are comparable to those of the clinical candidate MEDI0382 on reverse hepatic steatosis, suggesting potential for treating nonalcoholic steatohepatitis.

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