Initiate Lifestyle Changes plus Metformin, Add Second Agent If Not at Goal

Lifestyle interventions and metformin (Glucophage) therapy should be initiated concurrently when type 2 diabetes is diagnosed, emphasize the updated consensus guidelines for the management of hyperglycemia in type 2 diabetes issued late last year by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes and published in Diabetes Care (2006; 29:1963-1972) and Diabetologia (2006; 49: 1711-1721).

A second medication should be added in patients who are not reaching glycemic goals within 2 to 3 months after initiating lifestyle modifications plus the maximum tolerated dose of metformin. The second agent could be insulin, a sulfonylurea, or a thiazolidinedione (TZD).

“It is no longer acceptable to delay the initiation and adjustment of glucose-lowering therapy when metabolic goals are not being met,” said David M. Nathan, MD, chair of the consensus statement panel. A new treatment algorithm (Figure) emphasizes the goal of reaching glucose levels at or around the nondiabetic target range.

New HbA_1c Goals
A hemoglobin (Hb) A_1c level of ≥7% should serve as the “call to action” to initiate or adjust therapy in patients with type 2 diabetes. The goal is to reach an HbA_1c level as close to the nondiabetic range as possible, or at the very least to reduce the HbA_1c to <7%.

The upper limit of the nondiabetic range of HbA_1c is 6.1%. The most recent goals recommended by the ADA and the European Union–International Diabetes Federation are an HbA_1c level of <7% and <6.5%, respectively.

Weight Loss
In addition to improving glycemic control, weight loss has been shown to reduce concomitant cardiovascular risk factors, including blood pressure and atherogenic lipid profiles. “Weight loss of as little as 4 kg will often ameliorate hyperglycemia,” the authors write.

Drug Therapy
The ability of glucose-lowering therapy to prevent the long-term complications of diabetes depends primarily on the ability to reach glycemic control rather than on the drug used.

Therefore, deciding which antidiabetic medication to prescribe to the specific patient should be evaluated based on the HbA_1c levels achieved and the treatment side effects, tolerability, and costs.

Virtually all patients with type 2 diabetes require lifestyle interventions designed to promote weight loss and increase physical activity. However, the consensus statement does not provide specific diet and exercise program recommendations.

A variety of antidiabetic drugs are available for use as monotherapy (Table), including insulin, sulfonylureas, TZDs, alpha-glucosidase inhibitors, the glucagonlike peptide-1 agonist exenatide (Byetta), and the amylin agonist pramlintide (Symlin).

The ambient level of glycemic control should be a major factor in selecting a class or a specific medication within the class; agents with greater and more rapid glucose-lowering effects are recommended for patients with markedly elevated HbA_1c levels.

Most patients will eventually re-quire more than 1 medication. When adding a second or a third antihyperglycemic drug, consider the synergy of particular combinations and potential drug interactions.

For patients with severely uncontrolled diabetes with catabolism, insulin therapy (on top of lifestyle interventions) is the optimal approach. Initiate or intensify insulin therapy to achieve desired glycemic goals.

ONLINE EXTRA
Hyperglycemia Management: Guidelines At-a-Glance

• Glycemic goal: HbA_1c <7%
• Lifestyle interventions, with rare exceptions, for all patients
• Weight loss improves glycemia and cardiovascular risk factors, but long-term maintenance is difficult; most patients will require medications
• Initiate therapy with lifestyle interventions and metformin
• Add a second medication if initial therapy fails to reach glycemic goals in 2-3 mo
• When adding antihyperglycemic drugs, consider the synergy of any particular combination: agents with different mechanisms of action will have the greatest synergy
• Add/intensify insulin if lifestyle interventions, metformin, and a second drug do not result in glycemic goal

Source: Nathan D, et al. Management of hyperglycemia in type 2 diabetes: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006; 29:1963-1972.