Recently, a debate has been raised regarding the place and the role of sulfonylureas (SU) amongst the armamentarium of drugs available for treatment of hyperglycemia in subjects with type 2 diabetes mellitus. With the advent of new drugs, SUs are being relegated and denigrated by some authorities contrary to present recommendations by various organizations e.g. American Diabetes Association, European Association for the Study of Diabetes and International Diabetes Federation. In this article, the advantages of SUs over the new agents in terms of their well established and proven better efficacy as well as their short term and long term (over 50 years) safety based on extensive literature data are documented. Moreover, lower costs of SUs render them to be far more cost effective when compared to new agents and therefore make them affordable in many regions of the world. Additionally, SUs are probably the initial drugs of choice in lean subjects with prediabetes and type 2 diabetes because they are the most effective secretogogues and major pathophysiologic mechanism of altered glucose metabolism in lean subjects is the decline in insulin secretion and not rising insulin resistance. Furthermore, SUs are also the most cost effective 2nd line agents in obese subjects with type 2 diabetes on lapse of glycemic control while receiving metformin. Finally, with progression of the disorder, the most cost effective combination of 2 oral agents in conjunction with basal insulin remains to be metformin and SUs. Many studies have documented a significantly greater extra pancreatic effect of glimepiride in comparison to other SUs probably because of its unique property in enhancing insulin sensitivity in conjunction with its ability to stimulate both 1st and 2nd phase insulin secretion. These characteristics may contribute to its greater efficacy with lesser hypoglycemia when compared with other SUs. Lack of hypoglycemic effect of metabolites of glimepiride may also be responsible for lesser hypoglycaemia. Moreover, metabolism of glimepiride performed partially by the liver and partially by the kidneys may render it suitable and adaptable to be administered safely in subjects with hepatic or renal dysfunctional as well as elderly. Finally, the documentation of its pleiotropic effects in lowering of cardiovascular surrogate markers, improving thrombotic milleau by reducing platelet aggregation factors along with improvement in glycemic control and its preferential binding to SU receptors on the pancreatic beta cells rather than myocardium may be responsible for providing better cardiovascular outcomes in comparison to other SUS and thus make it a better choice amongst SUs in subjects with or without presence of cardiovascular disease. Additionally, once daily administration because of lasting efficacy for 24 hours based on its half life is likely to enhance compliance on the part of patients and assist in attaining and maintaining desirable glycemic control. Therefore, SUs still deserve to be major players in management of hyperglycemia in subjects with type 2 diabetes mellitus and glimepiride may be the best choice amongst SUs because of its long term record regarding efficacy and safety in diverge population of subjects with type 2 diabetes mellitus.
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