A1C Targets Should Be Personalized to Maximize Benefits While Limiting Risks

A set of guidance statements recently published by the American College of Physicians (ACP) advocates relaxation of goals for control of glycated hemoglobin (A1C) by people with type 2 diabetes (T2D) (1). This publication advises that “clinicians should reevaluate HbA1c levels and revise treatment strategies on the basis of changes in the balance of benefits and harms.” Specifically, it proposes reducing pharmacotherapy for any person when A1C is <6.5%, seeking a level between 7 and 8% for “most patients,” and aiming only to minimize symptoms without any specific A1C goal for those over age 80 years or with chronic medical conditions likely to limit life expectancy. These recommendations are at odds with those of other professional organizations, including the American Diabetes Association (ADA) (2–5). We believe the ACP recommendations fail to consider several important bodies of scientific evidence, and if they are widely adopted in clinical practice, the recent progress in management of diabetes may be threatened. Each of the ACP’s recommendations requires specific comments. These will be followed by a more general discussion of our concerns. The ACP’s main justification for decreasing therapy whenever A1C is <6.5% is the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial’s finding of ∼20% increased mortality—mostly from cardiovascular (CV) events—when the median A1C attained by intensive treatment was 6.4% (6). However, this generalized advice does not acknowledge experience in other trials. In contrast to ACCORD, the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (7) and the Veterans Affairs Diabetes Trial (VADT) (8), which similarly enrolled high-risk patients and sought A1C levels <7%, did not show increased short-term CV risk or mortality. Importantly, the newly diagnosed, low-risk participants in the UK Prospective Diabetes Study (UKPDS) also showed no tendency toward increased early mortality …