Metabolic Aspects of Five Commonly Used Non-Insulin Anti-Hyperglycemic Medications in Type 2 Diabetes

Type 2 diabetes is a growing public health challenge while carrying a significant health burden for the patient suffering from it. The worldwide prevalence of diabetes in 2019 was estimated to be 9.3%. Fortunately, a number of drug classes are now available for the medical management of hyperglycemia in this disorder. Metformin and the sulfonylureas are time-tested medications that are effective and inexpensive as first-line medications. The incretin-based therapies, namely the glucagon-like peptide-1 agents and the dipeptyl peptidase-4 inhibitors, offer novel mechanisms of gut hormone and appetite modulation. The former combine weight loss and cardiovascular benefit with glycemic control. The sodium glucose cotransporter-2 inhibitors have a unique glycosuric action that lowers glucose while being of value in congestive heart failure. Almost all these classes of antihyperglcyemic agents can be used in various combinations with one another as well as with different insulin regimens. This article shows the chemical structures and summarizes the mechanistic and therapeutic aspects of the five main classes of noninsulin glucose-lowering medications approved for use in patients with type 2 diabetes.