Novel Therapeutic Approaches in Diabetes

This chapter deals with novel therapeutic approaches, predominantly for type 2 diabetes. Incretin-based therapies utilize the effects of glucagon-like peptide-1 (GLP-1), which stimulates insulin and inhibits glucagon secretion in a glucose-dependent manner. Incretin-based therapies comprise injectable GLP-1 receptor agonists and orally active dipeptidyl peptidase-IV inhibitors. Both have a low hypoglycaemia risk. GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, dulaglutide, albiglutide) reduce glycated haemoglobin levels more effectively than oral antidiabetic agents do and lead to weight loss as well as a slight decrease in systolic blood pressure. The most common side effects are nausea and fullness, especially during the start of therapy. Dipeptidyl peptidase-IV inhibitors (alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin) are not inferior to sulfonylureas, causing significantly less hypoglycaemia and not inducing weight gain. Specific adverse effects have not been discovered yet, and cardiovascular safety has been demonstrated in respective studies. Sodium-glucose transporter-2 inhibitors (dapagliflozin, canagliflozin, empagliflozin) were introduced recently. They block the tubular reabsorption of glucose in the kidney and represent an insulin-independent mode of action, with low hypoglycaemia risk and allowing weight loss. The most common side effects are genital and urinary tract infections. Other novel drugs in development (G-protein-coupled receptor agonists, interleukin-1 antagonists) are also described.