Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Greater understanding of the complex and multifactorial pathogenesis of type 2 diabetes mellitus (T2DM) has informed the development of several new classes of glucose-lowering therapiesMetformin remains the first-line pharmacotherapy for patients with T2DM, whereas the use of other well-established agents, such as sulfonylureas, meglitinides, pioglitazone and α-glucosidase inhibitors, varies in different regionsAgents that enhance incretin activity (DPP-4 inhibitors), supplement endogenous GLP-1 (GLP-1 receptor agonists) or increase urinary glucose elimination (SGLT2 inhibitors) have low risk of hypoglycaemia and can assist weight controlTreatment with two or three agents with different modes of action can be required as T2DM advances, and insulin therapy is required if other agents are unable to maintain adequate glycaemic controlGlycaemic targets and the choice of glucose-lowering agents should be customized to meet the needs and circumstances of individual patients, which could be facilitated by future developments in pharmacogenomicsAlthough the balance of benefits and risks for different agents varies between individual patients, early, effective and sustained glycaemic control delays the onset and reduces the severity of hyperglycaemia-related complications