4.6 Article

Future directions in obesity pharmacotherapy

Journal

EUROPEAN JOURNAL OF INTERNAL MEDICINE
Volume 93, Issue -, Pages 13-20

Publisher

ELSEVIER
DOI: 10.1016/j.ejim.2021.04.024

Keywords

Obesity; Pharmacotherapy; Glucagon-Like Peptide 1; Appetite; Weight loss; Islet Amyloid Polypeptide; Body Weight Maintenance; Energy metabolism; Type 2 diabetes

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There is a growing need for more effective treatment of obesity and its complications, with current medications falling short of the efficacy seen with bariatric surgery. Gut peptide analogues are leading the way in clinical development and are likely to meet regulatory requirements soon. Early-stage drug development targeting different energy balance pathways may lead to more complex and personalized treatment guidelines.
There is a growing unmet need for more effective treatment of obesity and its complications. While current antiobesity medications are effective and offer real clinical benefits over diet and lifestyle interventions, they cannot meet the levels of efficacy and reduction of hard endpoint outcomes seen with bariatric surgery. As knowledge on the control of body weight unravels, the complexity of this physiology opens the opportunity to new druggable targets. Currently, gut peptide analogues such as semaglutide, a glucagon like peptide-1 (GLP-1) receptor agonist, and the dual agonist GLP-1 and gastric inhibitory polypeptide (GIP) tirzepatide are the furthest advanced in clinical development and seem likely to meet current regulatory requirements within the next year or so. However, current regulatory requirements are out of step with the efficacy of new compounds and concepts relating to obesity and its complications. Many other drugs in early development will target different pathways of energy balance, raising the possibility of drug combinations to maximise efficacy as for other chronic disease such as hypertension and diabetes. This will allow more complex and personalised guidelines to evolve.

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