The number of people suffering from insulin-independent type 2 diabetes mellitus (T2DM) is ever increasing on a yearly basis. Current anti-diabetic medications often result in adverse weight gain and hypoglycemic episodes. Hypoglycemia can be avoided with glucagon-like peptide (GLP)-1 receptor agonists, which are expensive and require daily injections that may result immune activation. This study demonstrates the use of non-viral vector based oral delivery of GLP-1 gene through enterohepatic recycling pathways of bile acids. Oral administration of the plasmid DNA (pDNA) encoding GLP-1 decreased diabetic glucose levels to the normoglycemic range with significant weight reduction in a high-fat diet (HFD) induced diabetic mouse model and a genetically engineered T2DM rat model. This novel oral GLP1 delivery system is an attractive alternative to treat late-stage T2DM conditions that require repeated insulin injection and can potentially minimize the occurrence of hypoglycemic anomalies.

患有非胰岛素依赖型2型糖尿病（T2DM）的人数逐年增加。当前的抗糖尿病药物经常导致不良的体重增加和降血糖发作。胰高血糖素样肽（GLP）-1受体激动剂可以避免低血糖症，后者价格昂贵，需要每天注射，可能会导致免疫激活。这项研究表明通过胆汁酸的肝肠循环途径，使用基于非病毒载体的GLP-1基因口服给药。在高脂饮食（HFD）诱导的糖尿病小鼠模型和基因工程改造的T2DM大鼠模型中，口服施用编码GLP-1的质粒DNA（pDNA）可将糖尿病葡萄糖水平降至正常血糖范围，并且体重显着降低。