Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A Consensus Statement From the American Diabetes Association and the European Association for the Study of Diabetes : Response to Nathan et al.

The recently published consensus treatment algorithm of the American Diabetes Association and the European Association for the Study of Diabetes (1,2) is an attempt to simplify the management of hyperglycemia in patients with type 2 diabetes. The goal, obviously, is to provide physicians with a tool that will allow them to attain the best outcomes for their patients. The guiding principles as outlined by the authors were cost, evidence-based clinical trials, and experience with long-term use. Although emphasizing the early initiation of pharmacologic therapy with metformin is a welcome strategy, several major features of the algorithm significantly limit its ability to achieve the best outcomes. Three such features are the therapeutic target A1C of 7.0%, the failure to recognize the importance of achieving postprandial glucose control, and the heterogeneity of the pathogenesis of phenotypic type 2 diabetes. A philosophical problem is the rejection of the value of newer, well-proven treatments because they lack multiyear clinical trials. This has the potential result of depriving diabetic patients the benefits of new and unique agents for years. Current data do not support the lack of further therapeutic efforts when A1C reaches 7.0%. The U.K. Prospective Diabetes Study (3) data, as well as other data, indicate that there is no glycemic threshold for microvascular complications. The Epic-Norfolk Study (4) indicated that cardiovascular mortality increases when A1C exceeds the mean normal range (∼5.1%). Many studies presented at the American College of Endocrinology/American Association of Clinical Endocrinologists (ACE/AACE) Glycemic Control Implementation Consensus Conference (5) showed that A1C values <6.5% are achievable safely with combination pharmacologic therapy. The point of decreasing therapeutic efforts when A1C approaches 6.5%, as recommended by ACE and the International Diabetes Federation, is more closely supported by evidence than the 7.0% value in the present algorithm. Cost-effectiveness of reaching 6.5% has not been studied but may be inferred by the anticipated reduction in glucose-related complications. The failure to emphasize the importance of postprandial glucose in achieving A1C targets in the algorithm limits its ability to help patients reach glycemic goals. Postmeal glucose excursions have been shown to have a greater effect in A1C elevations than fasting glucose in patients as their A1C levels decrease from 8.4% toward normal (6). Other studies comparing glargine and mixed insulins have yielded mixed results. Recent measurements with continuous glucose monitoring have confirmed the importance of controlling postprandial glucose excursions to achieve target A1C levels. Furthermore, there is robust experimental data relating postchallenge hyperglycemia to endothelial dysfunction and increased oxidative load. Despite strong biologic plausabilty, the clinical significance of this has not yet been established. The clinical benefit of targeting postprandial glucose, however, has been demonstrated by Esposito et al. (9) and Chiasson et al. (10). The therapeutic agent universally recommended as initial therapy, metformin, has little effect on postprandial glucose excursions, while agents excluded, such as exenatide, α-glucosidase inhibitors, rapid-acting insulin secretogogues, short-acting insulin analogues, and pramlintide are particularly beneficial in treating postprandial glucose excursions. The concept that all type 2 diabetic patients have the same pathogenesis and should receive the same treatment is not supported by large epidemiologic studies and genetic analysis. In summary, simplification, while theoretically a useful concept, does not always allow for the best results, and perhaps a more comprehensive algorithm would provide for better patient care. An example of a more inclusive algorithm is the ACE/AACE Diabetes Treatment Roadmap, available at www.aace.com/pub.