Benefits of combination therapy of insulin and oral hypoglycemic agents.

Abstract

I N THE 40 years since their introduction, oral hypoglycemic agents have become the cornerstone of pharmacologic therapy in type 2 diabetes mellitus. The 5 classes of oral agents now available are sulfonylureas, meglitinides, thiazolidinediones, biguanides, and -glucosidase inhibitors. However, initial therapy with any of these agents ultimately fails as the result of a gradual loss of -cell insulin secretory response to glucose. Treatment with an oral agent is often initiated as monotherapy; as glycemic control progressively worsens, a second agent is added in combination. The reported failure rates for single oral agents—5% to 20% per year— suggest that single oral therapy in type 2 diabetes succeeds for approximately 5 years. When therapy with multiple oral agents fails, exogenous insulin is required and is usually added to 1 or more of the existing regimen of oral agents. A large body of evidence suggests that insulin therapy should be initiated earlier in diabetes treatment and in combination with an oral agent to restore and maintain glycemic control, thus possibly reducing comorbidities of diabetes and sparing the remaining -cell function. Two outcomes of the United Kingdom Prospective Diabetes Study (UKPDS) were the apparent difficulty in maintaining constant glycemic control with insulin alone and the association of insulin monotherapy with weight gain and hypoglycemic events. As a result, combination therapy with oral agents and insulin has been further evaluated in several studies in an effort to achieve better long-term glycemic control with reduced insulin dosage and improved weight and lipid profiles.