Combined Therapy With Insulin Plus Oral Agents: Is There Any Advantage?

Abstract

Physicians in many countries use combinations of antihyperglycemic agents to achieve the best glycemic control possible under the conditions faced by individual patients with type 2 diabetes. This widespread use of combined therapies, including oral agents combined with insulin, suggests that the diabetes community accepts the value of this tactic. A routine need for combined therapies was explicitly acknowledged by the investigators in the U.K. Prospective Diabetes Study. Review of the results of 9 years of monotherapy with various agents in the U.K. Prospective Diabetes Study found that fasting plasma glucose (FPG) was kept below 7.8 mmol/l (140 mg/dl) in only 18% of participants using metformin, 24% using a sulfonylurea, and 42% using insulin (1). Corresponding values for keeping A1C below 7% were 13% with metformin, 24% with a sulfonylurea, and 28% with insulin. Regardless of which agent was used as initial therapy, a progressive worsening of glycemic control ensued, largely because of a gradual decline of endogenous insulin production. A substudy embedded in the U.K. Prospective Diabetes Study compared early addition of basal insulin to a sulfonylurea with insulin alone and showed that over 6 years of treatment the combined regimen achieved lower median A1C (6.6 vs. 7.1%) and also less major hypoglycemia (1.6 vs. 3.2% annually) (2). The U.K. Prospective Diabetes Study investigators concluded that “the majority of patients need multiple therapies to attain these glycemic targets in the longer term” (1). However, combined therapy with oral agents and insulin has not been accepted as desirable by all experts. This article describes an argument in favor of combined therapy in a recent debate examining the advantages and limitations of this approach. Because reports of various combined regimens have been summarized previously, consistently showing better glycemic control with combined therapy (3–6), this article will not systematically …