Point: Recent Long-Term Clinical Studies Support an Enhanced Role for Thiazolidinediones in the Management of Type 2 Diabetes

Abstract

The treatment options for type 2 diabetes were for many years limited to sulfonylureas, metformin, and insulin. However, in the last decade or so, a number of new oral and injectable agents have been introduced including the thiazolidinediones, incretin-related compounds, and “designer” insulins. Despite these additions to practitioners' armamentarium, attainment of optimal glucose control has remained largely elusive, in large part because type 2 diabetes is a progressive disease and health care professionals have failed to initiate combination therapy, including insulin, in a timely fashion. With near-normoglycemia treatment targets, the approach to glycemic management currently being advocated by the American Diabetes Association (ADA), the European Association for the Study of Diabetes (EASD), and the Canadian Diabetes Association (CDA) includes earlier commencement of treatment and more aggressive use of combination therapy (1,2). With few exceptions, most of these therapeutic recommendations are based on relatively short-term studies and expert opinion, as there are few long-term, head-to-head comparisons that provide definitive evidence. The UK Prospective Diabetes Study (UKPDS) helped fashion the current approach to diabetes management. This long-term study reported in 1998 and demonstrated that improved glucose control is associated with a reduced risk of microvascular complications (3,4). Further, it suggested that none of the therapies used in the study—sulfonylureas, metformin, and insulin—were able to slow the progressive nature of type 2 diabetes. Thus, over the course of more than 10 years, glycemic control deteriorated in all treatment arms at a rate that paralleled that in the cohort that received the conventional lifestyle intervention. At the time this landmark study was undertaken, the recommendations for glucose control differed markedly from those of today, so that “rescue” therapy for participants randomized to the conventional treatment arm was only instituted at a fasting plasma glucose level of 15 mmol/l (270 mg/dl). …