The study of incretins spans more than a century and has revealed their essential role in glucose homeostasis and metabolic regulation. This understanding has led to the development of incretin receptor agonists as highly effective pharmacological agents for the treatment of such cardiometabolic diseases as type 2 diabetes and obesity, showing substantial benefits in glycemic control, body weight reduction, and cardiometabolic outcomes. However, their use is limited by adverse events, most commonly gastrointestinal intolerance, along with ongoing safety concerns regarding pancreatic, renal, and ophthalmologic effects. Although incretin-based therapies have fundamentally reshaped the management of diabetes and obesity, continued innovation in drug design and delivery holds promise for expanding their applicability, improving patient adherence, and reinforcing their role as a cornerstone of metabolic disease management and beyond. This review summarizes the historical development, molecular design, and clinical relevance of incretin-based therapies, with particular emphasis on approved agents used in current clinical practice.

Isolation of pancreatic islets for single-cell RNA sequencing (scRNA-seq) remains technically challenging because enzymatic digestion, mechanical dissociation, and subsequent purification can cause cell loss, aggregation, and processing-induced transcriptional changes. This study aimed to adapt a practical gradient-free alternative for preparing murine pancreatic islets for downstream single-cell transcriptomic analysis while reducing the number of sample-processing steps. The workflow combined intraductal perfusion of the pancreas with 3 mL of a collagenase solution through the common bile duct, controlled enzymatic digestion at 37 °C, performed manual islet selection without density-gradient purification, and achieved gentle dissociation with Accutase and EDTA. DNase I was included in all post-digestion steps to limit cell aggregation. The protocol was evaluated using pancreatic islets from BKS.Cg-Dock7^m +/+ Lepr^db/J mice, a model of type 2 diabetes. Compared with Ficoll-based purification, the gradient-free protocol provided viable cell yields within a similar range while eliminating density-gradient preparation, an 18 min gradient centrifugation step, two subsequent wash centrifugations, and the associated transfer and dilution steps. The resulting scRNA-seq library showed satisfactory quality-control (QC) characteristics and retained the major endocrine populations, including β-, α-, δ-, and PP cells. The gradient-free sample also showed a lower overall stress-response score and lower expression of several immediate early genes, although heat shock- and endoplasmic reticulum (ER) stress-associated genes displayed heterogeneous patterns. These differences were considered descriptive because only one pooled scRNA-seq library was generated for each workflow. These findings support gradient-free isolation as a possible alternative to Ficoll-based purification for preparing murine pancreatic islets for scRNA-seq analysis.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established treatments for obesity and type 2 diabetes mellitus, but gastrointestinal barriers constrain oral delivery of peptide therapeutics. Genetically engineered microorganisms have been investigated as intestinal sources of GLP-1-related therapeutic molecules. These platforms produce GLP-1 or GLP-1-derived peptides, express modified GLP-1RAs or fusion proteins, or release effectors that stimulate endogenous GLP-1 secretion. Preclinical studies have reported improvements in glycemic measures and, in some models, reductions in body weight or weight gain. However, recombinant product expression and treatment-associated effects are more consistently demonstrated than exposure to intact biologically active products in vivo, receptor or pathway dependence, and the contribution of the engineered construct relative to the microbial chassis. Proteolysis, mucus interactions, restricted epithelial permeability, and receptor localization constrain access to intestinal and systemic targets. This review critically evaluates the preclinical evidence for GLP-1-oriented engineered microorganisms, with emphasis on intestinal target accessibility, local and systemic mechanisms, microbial chassis and genetic design, and the safety, manufacturing, and regulatory requirements for clinical translation.