Introduction: Obesity treatment is evolving rapidly with the emergence of agents targeting incretin receptors. Retatrutide, a triple agonist of these receptors, shows promise in obesity management.
Areas covered: Retatrutide, in phase-2 trials, exhibited significant reductions in glycated hemoglobin (HbA1c) and dose-dependent weight loss in individuals with type 2 diabetes mellitus (T2DM). In non-T2DM individuals, it produced substantial weight loss and improved glucose levels, albeit with gastrointestinal side effects. The role of glucagon receptor agonism in the management of heart failure and its potential impact on eating patterns have also been covered in this article.
Expert opinion: Although the reductions in HbA1c and dose-dependent weight loss among individuals with T2DM were significantly more for higher doses of retatrutide, it needs to be observed that the active comparator was dulaglutide, which is not approved for the treatment of obesity, at a dose of 1.5 mg, which is much lower than the highest approved dose of 4.5 mg. Dose-dependent increase in heart rate and incidents of mild to moderate cardiac arrythmias raise cardiovascular safety concerns and signify that carrying out long-term cardiovascular outcome trials (CVOTs) will be critical. In addition, retatrutide's potential in heart failure management is intriguing given the series of positive findings of semaglutide on cardiovascular outcomes.
Keywords: Retatrutide; diabetes mellitus; glucagon; heart failure; obesity.