GLP-1 and its synthetic analogs have emerged as significant therapeutic agents for the management of metabolic disorders, merging glycemic control with weight loss through innovative structural and delivery breakthroughs. This review provides a meticulous exploration of GLP-1, elucidating its origin, secretion, and the challenges associated with its clinical application due to its fragility in the presence of DPP-IV, resulting in a short half-life. To overcome this limitation, various modifications and delivery strategies to enhance the pharmacokinetic properties and therapeutic efficacy of GLP-1 analogs have been studied. The review delves into the intricacies of different modification approaches, including N and C-terminal modifications, Fatty acid Side chain Modifications, and Large Molecule Conjugation Modifications, highlighting their rationale and resulting improvements in half-life, stability, receptor binding, and bioactivity. Additionally, the importance of optimized delivery strategies to ensure sustained and controlled release of GLP-1 analogs is discussed. The culmination of these scientific advancements provides valuable insights for the development of more effective treatments for metabolic disorders, ultimately paving the way for improved patient outcomes in the realm of metabolic health.

Background: Conventional therapeutic and diagnostic approaches, despite improving clinical outcomes, remain limited by poor bioavailability, inadequate targeting, suboptimal pharmacokinetics, and systemic toxicity, particularly in complex diseases. To overcome this, nanomedicine has emerged as a transformative strategy, employing engineered nanoparticles to enhance drug stability, controlled release, targeted delivery, and diagnostic performance, thereby enabling theranostic applications. This review evaluates major nanoparticle platforms in therapy and diagnosis, comparing their mechanisms, applications, and challenges while highlighting their potential to advance precision medicine and theranostic strategies. Method: For providing the context and evidence, relevant literatures were sourced from Google Scholar, PubMed, and ScienceDirect using targeted keywords including “drug delivery,” “diagnostics,” “nanoparticles,” “nanomedicine,” “nano drug delivery,” “nanotheranostics,” “targeted therapy,” “controlled drug release,” “solid lipid nanoparticles (SLNs),” “lipid nano carriers (LNCs),” and “inorganic nanoparticles.” Although no strict time limit was applied during the literature search, clinical trial data were collected and analyzed up to January 2026. Given that clinical trial registries are continuously updated, the included trials represent the status at the time of data retrieval. However, it is pertinent to note that the earliest relevant studies appeared in 1973. Conclusions: This review highlights nanoparticle fundamentals, major material classes, mechanisms of action, and applications in targeted therapy, imaging, and theranostics. It also addresses translational barriers related to safety, scalability, biological complexity, and regulatory compliance. Overcoming these challenges through standardized characterization and interdisciplinary collaboration is crucial for clinical adoption. Future efforts should focus on AI-driven design, computational tools, smart nanomedicines, and advanced biosensing technologies to integrate nanoparticle-enabled precision diagnostics and therapy into routine clinical practice.