Pharmacotherapy of Oral Hypoglycemic Agents

The use of sulfonylurea in conjunction with a diet and exercise regimen continues to be the primary treatment modality for obese type II diabetics in the United States. These agents work to lower plasma glucose by several proposed mechanisms. Pancreatic mechanisms of action improve efficiency of the islet beta cells, and extrapancreatic mechanisms of action increase peripheral insulin-receptor sensitivity. Sulfonylureas are extensively metabolized in the liver. Depending on the specific agent, renally excreted metabolites with hypoglycemic activity may be produced and pose a threat to patients with impaired renal function. Accumulation of these metabolites can result in hypoglycemia, a common adverse reaction seen with the sulfonylurea. Other adverse reactions and their prevalence, presentation, and treatment are also presented. Clinically significant drug interactions of the sulfonylurea are tabulated and discussed. Because the sulfonlyureas have equivalent efficacy to each other, proper agent selection must be based on the metabolism and excretion characteristics, adverse reaction potential, and concurrent drug profile of the patient for whom the sulfonylurea is being selected. In patients who have not achieved adequate blood glucose control, combination therapy is sometimes initiated. Sulfonylurea-sulfonylurea and various sulfonylurea-insulin regimens are discussed. The importance of diabetic patient education is reviewed, including some basic instructions pharmacists can give to diabetics. The investigation of other oral hypoglycemic agents continues. Information of selected agents undergoing clinical trials in the United States is also reviewed.