Sulfonylureas: Basic Aspects and Clinical Uses

Abstract

This chapter describes the chemistry, mechanism of action, pharmacodynamics, pharmacokinetics, kinetics–effect relations, clinically beneficial and adverse effects of sulfonylurea drugs, as well as the efficacy of these agents in randomized‐controlled clinical trials and other studies. It also compares the different sulfonylurea compounds, especially in terms of differences in potency, rate of onset, and duration of action, and how such differences may contribute to different clinical profiles of the various compounds. In addition, some important interactions with other drugs are listed. Their appropriate place in the therapeutic armamentarium concerning type 2 diabetes is thoroughly discussed.

Development of Anti-diabetic Niosomes Formulation Containing Metformin and Gliclazide

“…Relatively Gliclazide is having longer biological half-life (6-15 h) depending upon individual and the dose is 80 mg two-three times a day with meals. Combination of Metformin-500 mg and Gliclazide-80 mg per tablet is available in India and it is to be taken two to three times a day to get required effect [3,4]. Recently, lipid and nonionic surfactant based drug delivery systems specifically niosomes have drawn much attention from researchers as potential carriers of various bioactive molecules that could be used for therapeutic applications.…”

Counterpoint: A Diabetes Outcome Progression Trial (ADOPT): Good for Sulfonylureas?

“…and in particular glibenclamide, on prevention of ischemic preconditioning in cardiac muscle are unwarranted (12). The issue of hypoglycemia with sulfonylureas is important and in some people can have a significant impact on quality of life through employment, recreation, or even falls and coma, particularly in the infirm elderly (13).…”

“…Glibenclamide is easily the most notorious member of its class as far as hypoglycemia is concerned, not just in clinical practice but also in terms of national serious adverse event reporting, particularly in association with renal disease (12,14). Indeed, this is one reason it is often chosen as a comparator in oral therapy drug trials, the other being its continued, widespread usage globally.…”

“…Indeed, this is one reason it is often chosen as a comparator in oral therapy drug trials, the other being its continued, widespread usage globally. Data on the extent of this problem are difficult to come by, but the incidence of events is probably 2-10 times higher than with other sulfonylureas (12). In the 2-year pioglitazonegliclazide study, gliclazide seems to have been associated with 10 -13% of patients having an event in 2 years (n ϭ 952 exposed), with no mention of events giving rise to serious health problems (3).…”

“…ADOPT is positive for sulfonylureas because the sister drugs of glibenclamide such as gliclazide and glipizide are widely available at generic prices while having a better safety profile regarding hypoglyce- mia (12). Put another way, over 3 years the glucose-lowering effect may be identical to a thiazolidinedione, but the costto-glucose-lowering ratio is some six times or so better for the sulfonylurea.…”