Why are we still in need for novel anti-obesity medications?

• Published in: The Lancet regional health. Europe Vol. 47; p. 101098
• Main Authors: Novikoff, Aaron, Grandl, Gerald, Liu, Xue, D. Müller, Timo
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2024; Elsevier
• Subjects: Anti-obesity medication (AOM); Diabetes; GIP; GLP-1; Internal Medicine; Obesity; Public Health; Viewpoint; Obesity; GLP-1; Diabetes; Anti-obesity medication (AOM); GIP
• ISSN: 2666-7762; 2666-7762
• DOI: 10.1016/j.lanepe.2024.101098

From the pioneering moment in 1987 when the insulinotropic effect of glucagon-like peptide 1 (GLP-1) was first demonstrated in humans, to today's pharmaceutical gold rush for GLP-1-based treatments of obesity, the journey of GLP-1 pharmacology has been nothing short of extraordinary. The sequential conceptual developments of long-acting GLP-1 receptor (GLP-1R) mono-agonists, GLP-1R/glucose-dependent insulinotropic polypeptide receptor (GIPR) dual-agonists, and GLP-1R/GIPR/glucagon receptor (GcgR) triple agonists, have led to profound body weight-lowering capacities, with benefits that extend past obesity and towards obesity-associated diseases. The GLP-1R/GIPR dual-agonist tirzepatide has demonstrated a remarkable 23% body weight reduction in individuals with obesity over 72 weeks, eclipsing the average result achieved by certain types of bariatric surgery. Meanwhile, the GLP-1R/GIPR/GcgR triple-agonist retatrutide achieves similar body weight loss (∼25%) in just two-thirds of the time, potentially surpassing the efficacy of Roux-en-Y gastric bypass. These remarkable achievements rightfully raise the question whether and why there is still need for novel anti-obesity medications (AOMs) in the future.