Advanced Transdermal Systems for Non-Invasive Delivery of GLP-1 Agonists in Treatment of Diabetes

Introduction: Diabetes mellitus is a chronic metabolic disorder requiring effective and patient-friendly drug delivery strategies. Conventional injectable therapies for glucagon-like peptide- 1 (GLP-1) receptor agonists face challenges such as injection-site reactions, poor adherence, and fluctuating drug levels. Transdermal patch (TDP) technologies are emerging as promising alternatives to address these limitations. Methods: Recent advances in TDP design employ nanoformulation techniques, microneedle arrays, permeation enhancers, thermoresponsive hydrogels, and biodegradable polymers. Hybrid strategies combine patches with iontophoresis or sonophoresis to optimize drug penetration. Lipid-based nanoparticles, sticky matrices, and bioreactive polymers further enhance patch stability, skin adherence, and sustained drug release. Results: Studies demonstrate that innovative TDPs enable controlled and prolonged GLP-1 agonist delivery, improving pharmacokinetic stability and reducing systemic fluctuations. Dissolving microneedle patches show efficient drug release upon gentle skin penetration, while hybrid and nanoparticle- based systems increase bioavailability and encapsulation efficiency. Enhanced adhesion supports consistent drug delivery, minimizing the need for frequent injections. Discussion: These technologies address major limitations of injections by reducing discomfort, improving compliance, and offering regulated, non-invasive delivery. However, clinical translation requires careful evaluation of safety, skin irritation, and performance differences across animal and human models. Integration with digital health tools may further enhance therapeutic impact. Conclusion: Novel TDP systems represent a patient-centered strategy for GLP-1 receptor agonist administration in diabetes care. By combining smart materials, permeation enhancers, and wearable technologies, they hold potential to improve glycemic control, adherence, and overall quality of life.