ABSTRACT
Introduction
The field of obesity medicine has evolved over the past several years. With greater understanding of its pathophysiology, obesity is regarded more as a chronic disease than a lifestyle choice. However, it is difficult to treat with lifestyle modifications alone due to the complexity of energy dysregulation. The availability of anti-obesity medications (AOMs) provides practitioners with more effective and sustainable ways to treat obesity.
Areas covered
This review briefly summarizes the weight loss efficacy of AOMs currently approved for long-term use and expands on their therapeutic potential beyond weight loss with particular focus on obesity-related comorbidities. Possible future AOMs with promising phase II or III data are also covered.
Expert opinion
The future of obesity medicine is in recognizing obesity as a disease and approaching treatment similarly to other chronic diseases. Lifestyle interventions alone are rarely sufficient in the treatment of chronic diseases, and pharmacotherapy often plays a necessary role in changing the course of disease. Current AOMs have proven efficacy in weight management and emerging therapeutic uses in obesity-related comorbidities, such as non-alcoholic fatty liver disease, obstructive sleep apnea, and polycystic ovarian syndrome. The development of new AOMs will further empower providers to deliver effective obesity management.
Abbreviations
AHI, apnea–hypopnea index
AOMs, anti-obesity medications
BMI, body mass index
BP, blood pressure
CV, cardiovascular
CVD, cardiovascular disease
CVOT, cardiovascular outcome trial
ER, extended-release
FDA, Food and Drug Administration
GABA, gamma-aminobutyric acid
GIP, gastric inhibitor peptide or glucose-dependent insulinotropic polypeptide
GLP-1, glucagon-like peptide-1
GLP-1R, glucagon-like peptide-1 receptor
HbA1c, hemoglobin A1c
HLD, high-density lipoprotein
HOMA-IR, homeostasis model assessment of insulin resistance
IBT, intensive behavioral therapy
LDL, low-density lipoprotein
MACE, major adverse cardiovascular event
MC4R, melanocortin-4-receptor
NAFLD, non-alcoholic fatty liver disease
NASH, non-alcohol steatohepatitis
NCT, national clinical trial
OSA, obstructive sleep apnea
PCOS, polycystic ovarian syndrome
PCSK1, proprotein subtilisin/kexin type 1
POMC, pro-opiomelanocortin
RCT, randomized controlled trial
REMS, Risk Evaluation and Mitigation Strategy
SGLT1, sodium-glucose transporter 1
SGLT2, sodium-glucose transporter 2
SR, sustained-release
T1D, type 1 diabetes
T2D, type 2 diabetes
TEAE, treatment-emergent adverse events
TID, three times a day
Declaration of interest
The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
Reviewer disclosures
One referee received funding from and served as a consultant for AstraZeneca, whose product, cotadutide, was briefly mentioned in the paper. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.
Article highlights
Pharmacotherapy is an essential component of a comprehensive obesity treatment plan that has proven efficacy in achieving long-term clinically significant weight loss with associated improvements in cardiometabolic risk factors
Current FDA-approved long-term anti-obesity medications have been evaluated for benefit in obesity-related conditions, such as type 2 diabetes, non-alcoholic fatty liver disease, and obstructive sleep apnea
Selection of an anti-obesity medication should be individualized to each patient, prioritizing medications that could potentially address multiple comorbidities and avoiding those that may confer a higher risk of harm
The mechanisms of action of emerging anti-obesity medications involve gastrointestinal peptide receptors, skeletal muscle differentiation, or central appetitive neural networks
The future of obesity pharmacotherapy will likely be a multi-targeted approach utilizing combinations of medications to address the complex pathophysiology of obesity
This box summarizes key points contained in the article.