The Fight Against Obesity Escalates: New Drugs on the Horizon and Metabolic Implications
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OBESITY TREATMENT (CM APOVIAN, SECTION EDITOR)
The Fight Against Obesity Escalates: New Drugs on the Horizon and Metabolic Implications Dimitrios Tsilingiris 1 & Stavros Liatis 1 & Maria Dalamaga 2 & Alexander Kokkinos 1
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review There is currently a steep rise in the global prevalence of obesity. Pharmaceutical therapy is a valuable component of conservative obesity therapy. Herein, medications currently in the phase of preclinical or clinical testing are reviewed, along with an overview of the mechanisms that regulate energy intake and expenditure. In addition, the current and potential future directions of obesity drug therapy are discussed. Recent Findings Although the current arsenal of obesity pharmacotherapy is limited, a considerable number of agents that exert their actions through a variety of pharmacodynamic targets and mechanisms are in the pipeline. This expansion shapes a potential near future of obesity conservative management, characterized by tailored combined therapeutic regimens, targeting not only weight loss but also improved overall health outcomes. Summary The progress regarding the elucidation of the mechanisms which regulate the bodily energy equilibrium has led to medications which mimic hormonal adaptations that follow bariatric surgery, in the quest for a “Medical bypass.” These, combined with agents which could increase energy expenditure, point to a brilliant future in the conservative treatment of obesity. Keywords Appetite . Energy expenditure . Gut peptides . Medical bypass . Obesity . Semaglutide . Weight loss
Abbreviations AgRP Agouti-related peptide BAT Brown adipose tissue BMI Body mass index cGMP Cyclic guanosine monophosphate CVD Cardiovascular disease DACRA Dual amylin/calcitonin receptor agonists DIO Diet-induced obesity DPP4 Dipeptidyl-peptidase-4 EE Energy expenditure EI Energy intake FDA Food and Drug Administration GCGR Glucagon receptor
GHSR1a GIP GLP-1 GLP1R GOAT NPY OXM POMC PYY RYGB SCT SG T2DM
Growth hormone secretagogue receptor type 1a Glucose-dependent insulinotropic peptide Glucagon-like peptide 1 Glucagon-like peptide 1 receptor Ghrelin-O-acyltransferase Neuropeptide Y Oxyntomodulin Proopiomelanocortin Peptide tyrosine-tyrosine Roux-en-Y gastric bypass Secretin Sleeve gastrectomy Type 2 diabetes mellitus
This article is part of the Topical Collection on Obesity Treatment * Alexander Kokkinos [email protected] 1
First Department of Propaedeutic Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 17 Ag. Thoma Street, 11527 Athens, Greece
2
Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece
Introduction Obesity has emerged as one of the most prominent morbidities of the current century, with a prevalence estimated soon to reach pandemic proportions [1]. The cornerstone of the conservative management of obesity, traditionally consisting of dietary management
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