Clinical efficacy of new thiazolidinediones and glinides in the treatment of type 2 diabetes mellitus

A central finding of the UKPDS was that in type 2 diabetic patients, tight glycemic control with HbA1c targets as close to the normal range as possibl e must be achieved to further reduce diabetes related-complications, -morta lity, and -cardiovascular disease, highlighting the need for new, optimized treatment strategies. With a focus on clinical efficacy, this paper discus ses the results from the 20 major therapeutical trials published in the yea rs 1997-1999, that evaluated the new insulinsensitizing thiazolidine, dione s Rosiglitazone and Pioglitazone and the new insulin-releasing potassium ch annel blockers Repaglinide and Nateglinide. While for Nateglinide, promisin g, but only preliminary data is available at current, Rosiglitazone, Piogli tazone, and Repaglinide have been shown appropriate for both mono- and comb ination therapy with current standard drug treatment of type 2 diabetes. Si milar to the known, older antidiabetic drugs, the new agents discussed have comparable blood glucose lowering potentials with a dose-related capacity of 0.5 to 1.5% HbA1c reduction. These beneficial effects were both seen in drug-naive patients previously treated with diet only and in combination th erapies when patients had previous antidiabetic standard drug treatment sug gesting effectiveness of glitazones and glinides also in more advanced stag es of the disease. Problems with adverse effects appeared minor although lo nge-range implications of weight gain, edema, lowering of hemoglobin, incre ase of total cholesterol for the glitazones, and hypoglycemia for glinides warrant further consideration. What becomes clear from the variety of most recent mono- and combination treatment studies with as much as five differe nt classes of antidiabetic drugs is that individually tailored therapies th at recognize quality of life parameters and target the predominant features of metabolic pathology (such as early postprandial versus lasting hypergly cemia, degree of insulin resistance, progressive loss of beta-cell function ) may become a feasible goal in the future.