Glucagon-like Peptide 1 and Estradiol in Metabolic Dialogue: A Scoping Review Protocol

This project constitutes the a priori protocol for a scoping review that aims to systematically map the existing preclinical and clinical evidence on the interplay between glucagon-like peptide-1 (GLP-1) and estradiol (E2) in the regulation of glucose and energy homeostasis. GLP-1 and estradiol are both key metabolic regulators that act on overlapping peripheral and central target tissues, and accumulating evidence suggests that their actions may be additive or, in specific contexts, synergistic. Despite growing interest in this interaction—particularly in the context of sex differences in metabolic disease and responses to incretin-based therapies—no comprehensive evidence synthesis currently exists. The primary purpose of this scoping review is to describe the available evidence addressing GLP-1–estradiol crosstalk across experimental models and human studies. The review will include in vivo and in vitro studies in mammalian models, as well as clinical studies across all ages, sexes, and health conditions, provided they assess interactions between GLP-1 and estradiol signaling or secretion with outcomes related to glucose metabolism and/or energy balance. The Joanna Briggs Institute methodology for scoping reviews will be appllied. Expected outcomes of this work include a structured mapping interaction concepts investigated to date. The results will be presented in tabular and/or graphical formats accompanied by a narrative synthesis, without quantitative pooling or meta-analysis.