More Treatment Options

If treatment with metformin does not sufficiently reduce HbA1c after about three months, practitioners are advised to proceed to a two-drug therapy, considering the benefits, side effects and risks of each medication, which are detailed in the position statement. (If metformin is contraindicated or not tolerated, a drug from the following categories should be selected initially.) With no order of preference, a combination therapy could include:

• Sulfonylureas

• Meglitinides

• Thiazolidinediones (TZD)

• Oral dipeptidyl peptidase-4 (DPP-4) inhibitors

• Injectable glucagon-like peptide-1 (GLP-1) receptor agonists

• Insulin (usually basal)

• Other drugs with more modest efficacy, as appropriate in special circumstances

The addition of a second drug should lower HbA1c by an additional 1%. If no response is seen in three months and adherence is good, the second drug should be discontinued and another with a different mechanism of action should be selected. If a two-drug combination does not or no longer achieves the glycemic target, a third drug with a complementary mechanism of action could be added. At this point, however, the authors advise that insulin will probably generate the best response. If a three-drug combination without insulin is tried, it should be closely monitored to avoid hyperglycemia.

“Ultimately, most patients will be treated with multiple daily doses of insulin,” said Morello, “since people with diabetes lose beta cell function over time.” The guidelines echo her assessment and state that insulin should be preferred in cases where degree of hyperglycemia as indicated by HbA1c above 8.5% “makes it unlikely that another drug will be of sufficient benefit.”

“For family-medicine providers, these guidelines are not as clear and may be a little harder to use. The biggest changes in practice are likely the wider use of GLP-1 receptor agonists and DPP-4 inhibitors, based on new information on efficacy and safety, and greater consideration of what the patient wants to do,” added Morello. “For primary-care providers, the downside of the greater complexity of the new guidelines may be a need for more education. The upside, though, is greater flexibility to design a treatment plan that reflects a patient’s needs and values while enabling them to better control their diabetes.”

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[1] Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. Medical management of hyperglycemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203. http://care.diabetesjournals.org/content/32/1/193.long

[1] Nathan DM, Buse JB, Davidson MB, Ferrannini E, Holman RR, Sherwin R, Zinman B. Medical management of hyperglycemia in type 2 diabetes mellitus: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2009;32(1):193-203. http://care.diabetesjournals.org/content/32/1/193.long

[1] VA/DoD Clinical Practice Guideline for the Management of Diabetes Mellitus. 2010. http://www.healthquality.va.gov/diabetes_mellitus.asp

[1] http://care.diabetesjournals.org/content/suppl/2012/04/19/dc12-0413.DC3/PositionStatementApril_2012NewsRelease.pdf