Is polypharmacy the future for pharmacological management of obesity?

Despite the rapidly increasing prevalence and associated costs of obesity, treatment options have remained remarkably limited. Some 650 million people are estimated to be living with but until recently lipase inhibitor orlistat was only mainstay pharmacological option, alongside dietary restriction. However, FDA approval glucagon-like peptide 1 receptor (GLP-1R) agonists, liraglutide semaglutide, for management it is hoped tide beginning turn. Roux-en-Y gastric bypass (RYGB) surgery remains most effective intervention weight loss, being attributable changes in energy intake/expenditure. This largely driven by substantial post-surgical modulation circulating gut hormones, including GLP-1, as well tyrosine–tyrosine (PYY), oxyntomodulin (OXM), glucose-dependent insulinotropic hormone (GIP), cholecystokinin (CCK) ghrelin. In order mimic these effects RYGB, there has been a recent surge interest pursuit both administration individual combinations development unimolecular hormone-based polypharmacy; single peptidic agents that co-activate several different signalling pathways. Dual agonist therapies such GLP-1/GIP co-agonist Tirzepatide, nearing regulatory non-alcoholic fatty liver disease (NAFLD) type 2 diabetes mellitus (T2DM). Given significant appetite reductions attained agents, drugs, along similar molecules development, will ultimately yield successful modern polypharmacy help manage current obesity epidemic.