The Individualized Target HbA1c: A New Method for Improving Macrovascular Risk and Glycemia Without Hypoglycemia and Weight Gain.

Both the DCCT and UKPDS trials demonstrated that improved glycemic control reduces microvascular complications. Inconclusive evidence, however, has remained on the question of the effect of glycemic control on macrovascular disease (with special emphasis on cardiovascular morbidity and mortality). In the last year, the data from four large trials were published, directly addressing this question (ACCORD, ADVANCE, VADT and UKPDS-80), yet the results were conflicting. Close inspection of the structure of three of these trials (ACCORD, ADVANCE and VADT) revealed inadequacies that may explain the unfavorable results, such as the inclusion of mainly elderly patients with previous macrovascular complications. It is not surprising that intensive glycemic control resulted in a rise of hypoglycemic events yet did not decrease macrovascular morbidity or mortality in these cohorts. On the other hand, the UKPDS-80 trial, a follow-up of the original UKPDS, showed that intensive glycemic control was beneficial when initiated in newly diagnosed patients. These results led us to develop a new individualized method of determining the target HbA1c based on the characteristics of the individual. This method considers the patient's possible benefit from glycemic control, the risk of suffering hypoglycemic events and consequences suffered from the hypoglycemic event. It is essential that the target HbA1c be tailored to the patient, with different goals set for the recently diagnosed "healthy" and young patient on the one hand, and the elderly patient with co-morbidities and polypharmacy on the other hand. We further suggest a method of comparing and choosing between the different hypoglycemic drugs available. Drugs should be considered not only based on their hypoglycemic effect but also on several other attributes such as effects on weight, glycemic durability, cardiovascular protection, individual experience with the drug, method of delivery and side effect profiles. Scoring the different attributes allows us to compare between different preparations and choose the most suitable drugs for each individual patient. Using our newly suggested system, a physician will first calculate the adequate HbA1c goal for his patient and then choose the drug that will best suit him, thus tailoring the treatment to the patients needs.