Abstract
Until the discovery of insulin in 1921 there were no effective treatments for diabetes mellitus. After the advent of long-acting insulin, the first oral agents, sulfonylureas became available in the mid-1950s, quickly followed (outside of the United States) by metformin. It was then another three decades before newer agents became available, with alpha glucosidase inhibitors, thiazolidinediones and meglitinides following in the 1990s. Since the turn of the century, several new classes have also been launched. But how do these agents fit into the management of type 2 diabetes? How does one choose which drug class to use after metformin? This review looks at the agents launched since 2000 and how and when they can be used. It also deals with some of the controversies that have arisen and how decisions have changed as a result, in particular moving away from the use of HbA1c as the driver for decision, but rather the cardiovascular safety of these agents and their use in the prevention of premature cardiovascular morbidity and mortality. Now that some of these agents have shown cardiovascular benefit, will this lead to a change in the treatment paradigm?