The importance of glycemic control: how low should we go with HbA1c? Start early, go safe, go low

Epidemiologic data indicate a continuous relationship between hemoglobin A1c (HbA1c) and risk for microvascular and macrovascular complications of diabetes. Intensive glycemic control reduces risk of microvascular complications in Type 1 and Type 2 diabetes, and long-term treatment and follow-up studies have shown that initial intensive control is associated with reduced cardiovascular risk. Recent intervention trials in older, high-risk patients with Type 2 diabetes have not shown a benefit of intensive control in reducing cardiovascular risk over a rather short-term follow-up period of up to 5 years, with some data indicating that intensive control accompanied by hypoglycemia is detrimental in patients with high cardiovascular risk. Indeed, hypoglycemia with current antidiabetic agents—primarily insulin and sulphonylureas—is the main limiting factor in achieving desirable levels of glycemic control. Still, the goal in treating both Type 1 and Type 2 diabetes should be to safely get HbA1c as close to normal as possible. In Type 2 diabetes, this goal should be tempered for the time being in patients with shorter life expectancy or co-existing cardiovascular disease or other co-morbidities, in whom a target of 7.0–7.5% may be advisable until we can demonstrate that lower targets in such patients can be safely achieved. Newer agents with lower risk of hypoglycemia—e.g., insulin analogues, incretin mimetics and incretin enhancers—may form an integral component of strategies for safely achieving lower HbA1c levels.