Emerging Advances in Oral and Injectable Anti-Obesity Pharmacotherapies: A Review of Current Evidence

Abstract

GLP-1-based therapies have substantially reshaped the management of type 2 diabetes and obesity, prompting rapid development of next-generation anti-obesity medications. Liraglutide, semaglutide, and the dual GLP-1/GIP agonist tirzepatide are currently approved and induce mean body-weight reductions of approximately 6-8% and up to 23%, but with attenuated effects in individuals with type 2 diabetes.
This review synthesizes progress made over the past 1-2 years in the development of anti-obesity pharmacotherapies, including mono-agonists of injectable and oral GLP-1 and injectable amylin, dual GLP-1/amylin agonists, GLP-1/GIP agonists and antagonists, as well as GLP-1/glucagon co-agonists and GLP-1/GIP/glucagon triple agonists currently in development for the treatment of type 2 diabetes, obesity, and metabolic liver disease. Looking ahead, achieving mean body weight reductions exceeding 25% now appears feasible
The adverse-event profile of GLP-1-based therapies is characterized primarily by gastrointestinal symptoms- including nausea, vomiting, constipation, and diarrhea- which can often be mitigated by initiating treatment at lower doses and employing a more gradual dose-escalation strategy.
GLP-1-based therapies are poised to increasingly shape treatment paradigms for obesity, type 2 diabetes, cardiovascular and kidney disease, fatty liver disease, sleep apnea, and osteoarthritis. Nevertheless, long-term weight maintenance remains a major unresolved challenge, and current evidence suggests that sustained pharmacological treatment may be required to mitigate weight regain.