GLP-1 Receptor Agonists: Emerging Indications, Limitations, and Future Directions

Objective: This article outlines the current trajectory of GLP-1 drugs, their future uses, and potential limitations, synthesizing evidence from randomized controlled trials, real-world studies, and emerging clinical literature. Background: There are a handful of GLP-1s currently on the US market (Dulaglutide, Liraglutide, Semaglutide, Tirzepatide) with FDA approval to treat diabetes, obesity, and, in some cases, sleep apnea and metabolic steatohepatitis. These therapies differ from earlier glucose-lowering agents by offering additional benefits beyond diabetes, such as improved weight management and cardiometabolic outcomes. As evidence of additional therapeutic effects continues to emerge, research efforts are expanding the potential clinical applications of GLP-1-based therapies. Evidence shows benefits beyond glycemic control, including cardiovascular, renal, and neurologic outcomes. Results: Currently, GLP-1s are limited by known side effects (primarily gastrointestinal) and other barriers to access, including cost. Data is limited, especially on long-term use, and new side effects are emerging; there is a need for more research on their use, and new drugs with modified mechanisms/dosage forms may help mitigate safety risks. Several adverse effects appear to be dose-dependent and influenced by patient-specific comorbidities. Conclusions: GLP-1s are indicated for treating adults with diabetes/obesity, but are highly effective at preventing their many complications and gaining traction for other therapies (cardio/metabolic, renal, hepatic, and more). Ongoing phase 3 trials and next-generation GLP-1 and dual-agonist therapies may help address current safety and accessibility limitations.