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[Comment] Twice the benefits with twincretins?

Rising global numbers of patients with obesity and diabetes and a scarcity of approved medical therapeutics with curative potential are major challenges for physicians, biomedical researchers, and health-care systems worldwide. Scientific breakthroughs such as discovering gut hormone-based polyagonists with preclinical efficacy and action profiles similar to gastric bypass surgery suggest that transformative medicines for obesity and type 2 diabetes might be within reach.1 Remaining uncertainties are the inclusion of glucagon receptor agonism as a driving factor in the promotion of energy expenditure and weight loss in some of the leading candidates for unimolecular coagonism targeting obesity and type 2 diabetes, because this action requires substantial buffering by incretin action to prevent detrimental effects on glucose metabolism.