Comparative safety of newer oral antidiabetic drugs.

Oral antidiabetic agents were introduced into clinical practice during the 1950s. Biguanides and sulfonylureas are still used extensively today and their safety and tolerability profiles are well defined. Developments and refinements within these classes have included the introduction of second- and third-generation sulfonylureas, the introduction of modified-release preparations, and the emergence of fixed-dose preparations with metformin and with novel drugs. The latter include the thiazolidinediones, agents with a putative genomic mechanism of action that have been under intense scrutiny since the emergence of severe hepatotoxicity with troglitazone. Recent concerns about thiazolidinediones have centred on the issue of oedema and the risk of precipitating heart failure in vulnerable patients. Only prolonged exposure will determine the long-term safety of thiazolidinediones. Rapid-acting non-sulfonylurea secretagogues appear to be effective and perhaps safer than sulfonylureas in some groups of patients with certain comorbidities (e.g., those with renal impairment). alpha-Glucosidase inhibitors have an excellent safety record and acarbose has been shown to retard the progression from impaired glucose tolerance to Type 2 diabetes. However, their use is limited by tolerability issues.