Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Nick Wytiaz University of Pittsburgh APPE – Care to the Underserved August 18, 2011 [email protected] Drug Information Question Appropriate Selection of a Second Generation Sulfonylurea Sulfonylureas are the oldest class of oral agents used for the treatment of type 2 diabetes. They work by stimulating the release of insulin from pancreatic beta cells, thereby increasing both basal and postprandial insulin secretion and generally lower blood glucose concentrations by approximately 20% and A1C levels by 1-2%.1 The sulfonylureas can be divided into two categories: first generation (acetohexamide, chlorpropamide, tolazamide, and tolbutamide) and second generation (glimepiride, glipizide, and glyburide). First generation agents are no longer recommended by current diabetes treatment guidelines (ADA [American Diabetes Association] and AACE [American Association of Clinical Endocrinologists) due to their increased side effect profile, primarily hypoglycemia, and increased frequency of dosing. The ADA currently considers second generation sulfonylureas the preferred 2nd line treatment option after metformin and lifestyle changes.2 The AACE considers these for add-on therapy to metformin in patients with elevated fasting plasma glucose and A1C 6.5- 9% or as part of a multi-drug regimen with metformin, in drug-naïve, asymptomatic patients with A1C > 9%.3 All sulfonylureas share the same mechanism of action, are equally effective when administered in equipotent doses, and have similar drug-drug interactions and adverse event profiles.1 Sulfonylureas do differ in their pharmacokinetic properties. The differences may be a factor when selecting a specific agent for a patient. Table 1. Parameters of Second Generation Sulfonylureas 4-7 Medication Onset Duration Metabolism Renal Active Half-life (hours) (hours) Excretion Metabolite (hours) Glimepiride 2-3 24 Hepatic 60% Yes 9 Glipizide 1-3 10-24 Hepatic 80-85% No 2-4 Glipizide SR 2-3 24 Hepatic 80% No 2-5 Glyburide 2-4 16-24 Hepatic 50% Yes 10 Glyburide, micronized 1 12-24 Hepatic 50% Yes 4 Another main difference among the sulfonylureas is their propensity to cause hypoglycemia, the hallmark adverse effect of the class given their mechanism of action. Glyburide has been associated with the greatest risk for hypoglycemia, relative to other second generation agents. One study suggests that the risk for hypoglycemia with glyburide is almost 40% higher than glipizide.8 A meta-analysis also supported this finding, reporting a higher risk for hypoglycemia with glyburide compared to other sulfonylureas.8 However, the difference was not statistically significant. Still, the concern for hypoglycemia seems to be clinically significant as reflected by the ADA Consensus Guidelines, which recommend against the use of glyburide when initiating a sulfonylurea as add-on therapy. The potential risk for increased hypoglycemia with glyburide is most likely linked to its pharmacokinetic profile. Glyburide has a longer duration of binding to the pancreatic sulfonylurea receptor than other sulfonylureas, resulting in a relative higher degree of fasting hyperinsulinemia. In addition, the longer half-life and active metabolite may contribute to the hypoglycemic activity. Since multiple studies have demonstrated comparable clinical effectiveness and glycemic control for all the second generation sulfonyureas and cost is not an issue (all sulfonyureas are generically available), the selection of a specific agent comes down to the characteristics of the individual patient and the risk of hypoglycemia.1 Given the pharmacokinetic properties of the drugs and studies comparing the rate of hypoglycemia, initial treatment with glyburide is not recommended. For older patients and those with renal or hepatic dysfunction, sulfonyureas with shorter half-lives, such as glipizide, should be recommended and extended-release products (i.e. glipizide SR) should be avoided. Regardless of the agent chosen, initial treatment should start at a lower dose and then be titrated up slowly as tolerated by the patient. References: 1 McColloch DK. Sulfonylureas and meglitinides in the treatment of diabetes mellitus. In: Rose BD, editor. UpToDate; 2007. Available from: http://www.utdol.com/utd/index.do . American Diabetes Association. Standards of medical care in diabetes – 2011. Diabetes Care. 2011;34(Suppl. 1): S11–S61. 2 3 AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for Developing a Diabetes Mellitus Comprehensive Care Plan. Endocr Pract. 2011;17(Suppl 2):1-53. 4 Amaryl® [package insert]. New York, NY: Sanofi-Aventis US; 2006 Feb. 5 Glucotrol® [package insert]. New York, NY: Pfizer; 2006 Sep. 6 Micronase® [package insert]. Kalamazoo, MI: Pharmacia & Upjohn Co; 2002 Mar. 7 Glynase PresTab® [package insert]. Kalamazoo, MI: Pharmacia & Upjohn Co; 2006 May. 8 Selecting a sulfonylurea. Pharmacist’s Letter/Prescriber’s Letter. 2009;25(4): 250411.