A combined GLP-1 and CCK peptide enhances metabolism by activating both hormone systems in mice

C2816, a novel fusion peptide, induced a superior reduction in body weight in diet-induced obese mice compared to separate administration of its components.

• C2816 is a fusion of a GLP-1 receptor agonist and a cholecystokinin receptor agonist.
• In vitro assays indicated that C2816 maintained agonistic activity at both receptors but with lower potency than the individual components.
• Acute in vivo effects showed that C2816 increased cFos expression in brain regions associated with feeding behavior.
• C2816 reduced food intake in wildtype mice, but the effect was diminished in GLP-1 receptor-deficient mice.
• In sub-chronic studies, C2816 demonstrated a greater reduction in body weight in diet-induced obese mice than the combination of the parent molecules, although at a higher dose.

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