Addition of Basal Insulin to Oral Antidiabetic Agents: A Goal-Directed Approach to Type 2 Diabetes Therapy

Louis Kuritzky, MD


November 15, 2006

Abstract and Introduction


The objective of this article is to review current findings in the published literature on the efficacy of insulin therapy in combination with oral antidiabetic agents, with a focus on practical information that might help to provide an evidence-based template for selecting how best to combine oral agents and basal insulin in patients with type 2 diabetes.

Here we review the current oral agents used to treat type 2 diabetes, their mechanisms of action, and how they can be combined with insulin therapy to help patients achieve guideline-recommended glycemic goals. While practical advice exists for initiating a therapeutic regimen comprised of basal insulin and oral agent(s), direction as to appropriate therapy for individual patients with differing physiologic requirements is needed. Oral antidiabetic therapy in combination with insulin provides an effective therapeutic option for patients who are unable to achieve or maintain glycemic goals on oral therapy alone.


Despite the well-documented consequences of long-term uncontrolled hyperglycemia, the majority of patients with type 2 diabetes are not achieving the degree of glycemic control recommended by currently accepted guidelines. The 2006 American Diabetes Association (ADA) recommendations for glycemic control are listed as a glycosylated hemoglobin A1C (A1C) level < 7.0% and fasting plasma glucose (FPG) levels of 90-130 mg/dL (5.0-7.2 mmol/L), or as close to physiologic levels as possible without unacceptable hypoglycemia.[1] The American Association of Clinical Endocrinologists (AACE) has an even more stringent recommendation for an A1C level of ≤ 6.5%.[2] Despite this expert guidance, the National Health and Nutrition Examination Survey demonstrated that only 37% of adults with diabetes in the United States are achieving target A1C levels.[3]

When diet and exercise fail to provide adequate glucose control in type 2 diabetes, oral antidiabetic agents are usually prescribed as initial therapy. Although many patients initially attain control, over the long term there is generally a requirement for intensified and multidrug regimens; ultimately, oral agents alone cannot maintain satisfactory control in many individuals and therapy must be augmented by the addition of insulin. Indeed, newly diagnosed individuals with A1C levels > 10.0% are not likely to achieve goals on oral therapy alone and insulin therapy should be initiated.[2]

Normal pancreatic insulin secretion comprises 2 components: (1) a constant low level of secretion (basal secretion) to suppress glucose production between meals and overnight, and (2) spikes of higher-level secretion in response to rising glucose levels after meals (postprandial secretion). Therapy with basal insulin is a strategy that attempts to approximate the basal component of normal pancreatic insulin secretion that, in combination with oral therapy, may help patients achieve recommended glycemic goals.

Basal insulin most commonly is administered at night (in this article, we will refer to neutral protamine Hagedorn [NPH] insulin, insulin detemir, and insulin glargine as the agents administered as basal insulin). Because basal insulin activity is the primary source of fasting glucose control, basal insulin treatment is often thought of as only impacting the fasting glucose. However, effective basal insulin therapy can concomitantly lower meal-associated glucose levels through overall improvement in metabolic control[4] and can be a relatively simple and highly effective approach to insulin therapy, particularly early in the course of diabetes.[5] The benefits of combining basal insulin with oral agents for improved glycemic control are well established. Although there is expert guidance available for the primary care clinician on addressing hyperglycemia in type 2 diabetes patients,[6] how and when to combine the therapeutic options and which agents among the classes are best suited for combination are expanded upon in this article.

A number of different oral antidiabetic agents with distinct mechanisms of action are currently available. Practical information and guidance is needed for clinicians to make clinical decisions about use of these agents in combination with basal insulin.

This article outlines currently available oral antidiabetic agents and basal insulins and provides practical advice based on current clinical literature for choosing appropriate oral agents for use in combination therapy with basal insulin. Specifically, this report addresses appropriate agents and therapeutic options only for patients with type 2 diabetes, because oral agents are not appropriate treatment for patients with type 1 diabetes. The differing attributes of oral agents currently available for use in combination with insulin provide an opportunity for the physician to better individualize care for patients with type 2 diabetes.


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