Pharmacotherapy for Patients with Obesity

Abstract

Background: Although pharmacotherapy is not the cornerstone of obesity treatment, it is a valuable tool that could be considered for patients who have not had adequate benefit from lifestyle interventions or who have difficulty maintaining initial weight loss over longer periods.

Content: This review focuses on the role of antiobesity drugs, the mechanisms by which the drugs work, potential pharmacological targets in the neural control of food intake and regulation of body weight, the history of antiobesity drugs, a summary of efficacy and safety data from clinical trials, and the clinical application of pharmacotherapy. Currently, 5 approved drug therapies are available in the US for long-term weight management, with only 2 of these meeting the stronger Food and Drug Administration (FDA) criteria of 5% weight loss relative to a placebo after 1 year and others receiving approval based on the categorical criterion of the proportions of patients achieving 5% weight loss. Interpretation of the results of clinical trials conducted before regulatory agency approval is limited by high dropout rates; thus, the results might not be replicable in clinical practice settings. Many patients who are suitable candidates for pharmacotherapy are not using the new drugs due to lack of insurance coverage and high out-of-pocket costs.

Summary: With the availability of 4 new drugs since 2012, clinicians in the US now have more tools for long-term weight management. The quality of pharmacotherapy clinical investigations needs considerable improvement. Future research should focus on examining the mediators and moderators of response.

Fig. 1.. Schematic diagram showing potential pharmacological targets in the neural controls of food intake and regulation of body weight.

A selection of only key neurotransmitters, hormones, and other factors (normal font) and receptors (italic) are shown at their major sites of action. Abbreviations: AChR, cholinergic acetylcholine receptor; Adipo, adiponectin; AGRP, Agouti-related protein; AMY, amylin; ARα, α-adrenergic receptor; ARß, ß-adrenergic receptor; CART, cocaine- and amphetamine-related transcript; CB1R, cannabinoid receptor-1; CCK, cholecystokinin; CGRP, calcitonin gene-related peptide; DA, dopamine; DARs, dopamine receptors; ECs, endocannabinoids; FGF19/20, fibroblast growth factors 19 & 21; FGFRs, fibroblast growth factor receptors; GABA, gamma-aminobutyric acid; GABARs, GABA receptors; GLUT, glutamate; GUTRs, glutamate receptors; GLP-1, glucagon-like peptide 1; GLP-1R, glucagon-like peptide-1 receptor; IL-6, interleukin-6; INS, insulin; InsR, insulin receptor; Lep, leptin; LepR, leptin receptor; MCH, melanin-concentrating hormone; NT, neurotensin; NTR, neurotensin receptor; OPIO, opioids; OPIORs, opioid receptors; ORX, orexin/hypocretin; OT, oxytocin; POMC, proopiomelanocortin (α-MSH); PYY, polypeptide tyrosine-tyrosine; 5-HT, serotonin; 5-HTR2c, serotonin 2c receptor.