Application of Mass Spectrometry in GLP‑1 and Dual Incretin Therapeutics: A Scoping Review of Analytical, Clinical, and Structural Advances (2008–2025)

Background/Objectives: Glucagon-like peptide‑1 receptor agonists (GLP‑1 RAs) and dual incretin agonists, such as semaglutide and tirzepatide, have rapidly expanded beyond diabetes care into broader metabolic and societal contexts. At the same time, liquid chromatography–tandem mass spectrometry (LC‑MS/MS) and high‑resolution mass spectrometry (HRMS) have become essential for characterizing these peptide therapeutics. This scoping review aimed to map the application of mass spectrometry across the lifecycle of GLP‑1–based drugs, identify methodological trends, and highlight remaining knowledge gaps. Methods: A scoping review framework was used to capture heterogeneous evidence across analytical chemistry, pharmacology, and clinical re-search. Studies were eligible if they applied LC‑MS/MS or HRMS to GLP‑1 RAs or dual agonists in biological matrices or drug products. Using the Population–Concept–Context (PCC) structure, data were charted across analytical platforms, study aims, bi-ological matrices, and thematic domains spanning preclinical, clinical, structural, and societal investigations. Results: Twenty‑five sources published between 2008 and 2025 met the inclusion criteria. Early work focused on foundational pharmacokinetics and LC‑MS/MS quantification of GLP‑1 analogs. More recent studies incorporated HRMS, ion mobility, microfluidic chromatography, and automated peptide mapping to improve sensitivity, selectivity, and structural resolution. Clinical research focused on bioe-quivalence, perioperative safety, and expanding therapeutic use, while societal analyses documented rising public interest and evolving attitudes among healthcare profes-sionals. Structural and omics‑based studies provided insight into receptor engagement, biased agonism, and metabolic modulation. Conclusions: Mass spectrometry applica-tions in GLP‑1 research have advanced substantially, enabling deeper characterization of pharmacokinetics, molecular mechanisms, and clinical performance. Remaining gaps include long‑term safety assessment, standardization of digital methodologies, and integration of HRMS into regulatory frameworks. This review provides a foundation for future systematic evaluations and methodological development.