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This new line of pharmaceuticals maximizes the beneficial effects on energy and glucose metabolism while minimizing unwanted side-effects (Tschop and DiMarchi, Glucagon (Gcg) has many beneficial effects on energy homeostasis including the inhibition of food intake, as well as the ability to increase energy expenditure and activate BAT which all lead to a reduction in body weight (reviewed in Habegger et al., Glp1r/ mice treated with the GLP-1/Gcg coagonist experienced a reduction in body weight and fat mass but did not have improvements in glucose tolerance indicating that GLP-1R agonism is required to counteract the hyperglycemic effects of GcgR agonism (Day et al., Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone released from the K-cells of the small intestines and acts on the pancreas to potentiate GSIS (Miyawaki et al., An alternative approach aiming to maximize the efficacy of GLP-1 involves the delivery of nuclear receptor agonists to specific tissues characterized by the expression of GLP-1R

This weight loss was largely attributed to fat mass reduction rather than muscle loss

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GLP-1 Is Not Enough: Can Glucagon Fill the Energy Expenditure Gap

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DOI: 10.3389/fendo.2022.995007