Incretin Drug Revolution: The Challenges of Hope

Abstract

Over 800 million people worldwide meet the criteria for obesity, highlighting the need for safe and effective treatments. Recent advances reshaped the paradigm of adipose as an organ that regulates hunger, satiety, insulin sensitivity, and inflammation. Clinical obesity is a chronic condition linked to excess visceral adipose in which the health risk has already manifested. This definition reflects our understanding of obesity, rather than relating it to body size, weight-based conditions, or elevated body mass index. Clinical guidelines recommend pharmacotherapy for children and adults meeting the criteria for obesity. Because few independent diverse trials compare obesity drugs, doctors must resort to trial-and-error to predict usefulness. And the lack of diversity may impact drug safety for at-risk populations. For example, Black and Hispanic adults are at the highest risk for obesity, but few participated in drug trials. The discovery of incretins led to incretin-based hormone drugs that bind glucagon like peptide-1 or glucose-dependent insulinotropic polypeptide receptors. The media attention around these repurposed type 2 diabetes drugs brings hope for obesity treatment in clinical practice. Manufacturers market incretin drugs as a panacea for neurological, metabolic, and cardiovascular conditions. Filling a unique therapeutic gap between lifestyle modification and bariatric surgery, incretin drugs may help some people. Yet, with any medication, balancing benefits and risks optimizes health. Thus, long-term safety studies comparing incretin drugs in a diverse population are needed for the development of safe and effective treatments. Understanding the health benefits after bariatric surgery, drug therapy, and combination therapy may help guide future clinical practice.