An update on pharmacotherapeutic strategies for obesity

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.

KEYWORDS:

• Obesity
• anti-obesity medications
• obesity pharmacotherapy
• adiposity-based chronic disease
• weight
• weight loss
• weight 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.

Additional information

Funding

This manuscript was not funded.