Efficacy of Dual Glucagon and Glucagon-like Peptide-1 Receptor Agonists Across the Cardiometabolic Continuum: A Review of Current Clinical Evidence.

The global surge in cardiometabolic diseases, including type 2 diabetes, obesity, and cardiovascular diseases, has reached pandemic levels, demanding bold and innovative solutions. Dual glucagon (Gcg) and glucagon-like peptide-1 (GLP-1) receptor agonists represent a groundbreaking advancement in the treatment of this complex and interconnected spectrum of disorders. By harnessing the synergistic power of GLP-1 and Gcg receptor activation, these agents go beyond glucose lowering and weight loss, unlocking new frontiers in energy expenditure, fat oxidation, and liver fat reduction-key targets in conditions such as metabolic dysfunction-associated steatotic liver disease (MASLD). Emerging clinical evidence on agents such as survodutide and cotadutide has revealed striking improvements in glycated hemoglobin (HbA1c) levels and body weight, consistently outperforming traditional GLP-1 receptor agonists. More importantly, early evidence suggests meaningful benefits in cardiovascular and renal outcomes, positioning these therapies as comprehensive, disease-modifying tools for patients with multiple high-risk comorbidities. This review highlights the transformative potential of dual GLP-1/Gcg receptor agonists, providing a thorough examination of their mechanisms of action, clinical efficacy, and safety profiles across the cardio-metabolic continuum. As the limitations of existing therapies become increasingly evident, these next-generation agents are poised to redefine the standard of care across the cardiometabolic continuum, ushering in a new era of precision medicine for metabolic disease.