Newer Pharmacological Interventions Directed at Gut Hormones for Obesity.

The objective is to review the newer pharmacological interventions for obesity, specifically single, dual, and triple incretin receptor agonists that are either available or in the pipeline for treatment of obesity. The three incretin receptor targets are glucagon like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and glucagon. There are several approved single or dual incretin agonists which are administered subcutaneously daily (e.g., liraglutide) or weekly (e.g., semaglutide, dulaglutide, and exenatide QW), and experimental dual or triple incretin agonists. Other analogs of amylin, peptide YY, and oxyntomodulin, as well as a combination GLP1R agonist and GIPR antagonist are also being developed. Oral semaglutide (administered daily) is approved for type 2 diabetes and is on track for regulatory review for obesity. The review includes specifically perspectives on the effects of these mechanisms and pharmacological agents on gastric emptying which contribute to satiation and weight loss, in addition to the established evidence on effects on central mechanisms controlling appetite. In the future, it is anticipated that small molecule GLP-1 receptor agonists (e.g., oral danuglipron) will be developed. These pharmacological agents are having significant impact on glycemic control and obesity and their co-morbidities.