Mass Spectrometry Applications for GLP-1 and Dual Incretin Receptor Agonists: A Scoping Review Protocol

This research is a comprehensive scoping review that maps the application of mass spectrometry—specifically liquid chromatography-tandem mass spectrometry (LC-MS/MS) and high-resolution mass spectrometry (HRMS)—in the study of GLP-1 and dual incretin therapeutics, such as semaglutide and tirzepatide, published between 2008 and 2025. The primary purpose of this project is to synthesize a fragmented, multidisciplinary literature base to trace the evolution of these therapies from their initial pharmacokinetic testing to their widespread clinical use for type 2 diabetes and obesity. By utilizing a structured Population-Concept-Context (PCC) framework, the review maps methodological and conceptual trends across analytical chemistry, clinical pharmacology, and sociology. The study provides a detailed overview of various dimensions of GLP-1 research, including ultra-sensitive bioanalytical method development, the identification of structural "soft spots" vulnerable to enzymatic degradation, and the assessment of clinical safety and bioequivalence. Uniquely, the project also explores the broader societal implications of these drugs, analyzing the social media-driven "Ozempic phenomenon," shifting healthcare professional attitudes, and the impact of obesity bias. The expected outcomes of this review center on the identification of critical research gaps. The study highlights the urgent need for long-term safety assessments (such as weight rebound mechanisms and perioperative aspiration risks), the standardization of omics-based biomarkers, and the integration of HRMS technologies into evolving regulatory frameworks. Ultimately, this project establishes a foundational roadmap for future systematic reviews, directing upcoming research toward optimizing bioanalytical performance, confirming generic drug bioequivalence, and improving multidisciplinary clinical care. This protocol was developed a priori as part of the review’s methodological planning. It was registered retrospectively on OSF following completion of data charting to enhance transparency and reproducibility, consistent with PRISMA ScR Item 5.