By Annette M. Boyle

SAN DIEGO--Starting in 2010, the VA and DoD’s clinical practice guidelines recommended that clinicians add insulin therapy for patients with type 2 diabetes mellitus unable to meet HbA1c (A1c) goals with metformin and lifestyle modifications within two to six months.

- Candis Morello, PharmD, CDE

Increasing evidence shows that quickly reaching blood plasma glucose goals can stop or delay progression of diabetes, reduce the risk of microvascular complications and significantly lessen the economic burden of the disease.

With nearly 25% of the patient population being treated for diabetes — more than 1.4 million veterans — this is an especially critical issue for VA. Physicians’ busy schedules and patient resistance, however, have kept the use of insulin lower than it should be, said Candis Morello, PharmD, CDE, at the VA San Diego Healthcare System and associate professor of clinical pharmacy at Skaggs School of Pharmacy and Pharmaceutical Sciences at the University of California, San Diego.

“The 2010 guidelines aligned the VA with the recommendations of U.S. and European diabetes associations and represented a big change in approach for most physicians. Previous studies had shown that patients usually were 10 years into diabetes before insulin was started; now, we move quickly to get A1c at goal and often that means adding insulin,” Morello said.

“With the new stepwise approach, if a patient’s A1c is not at goal, typically below 7%, within two or three months of initiating treatment with metformin and lifestyle changes, then the clinician should step up therapy by adding basal insulin or a second oral agent such as a sulfonylurea,” she added.

The American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) advise clinicians to consider early use of insulin in any patient with extreme hyperglycemia, A1c levels above 10%, ketonuria or symptomatic diabetes. Metformin is typically the first drug used for other diabetic patients.

Basal insulin is the preferred second agent for patients who still have A1c levels 2% or more above goal (typically, 8.5% to 9.0%) after achieving the maximum tolerated dose of metformin. Other combinations can be considered for patients unable to use metformin or sulfonylurea, according to the joint VA/DoD guidelines. Those combinations may include thiazolidinediones, alpha-glucosidease inhibitors, meglitinides, dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide 1 (GLP-1) agonists.

“If the patient is still not at goal two or three months after adding another oral agent, then they should start on basal insulin,” added Morello. “The long-term safety and efficacy of three oral hypoglycemic agents is unknown.”

She noted that VA/DoD guidelines recommend the addition of insulin when two oral agents have failed to lower A1c levels sufficiently. Long-acting basal insulin generally is recommended for initial insulin therapy in the United States. Patients also might need short-acting insulin to manage glucose peaks following meals or in some other instances. There is no dose limit for insulin, as long as hypoglycemia can be avoided.

“Research and practice now support getting patients ‘tuned up’ faster. With this approach, patients achieve their goals much sooner and avoid the consequences of uncontrolled or insufficiently controlled hyperglycemia,” said Morello. “Achieving glycemic goals faster often comes with triglyceride control. And, the U.K. Prospective Diabetes Study showed that a 1% reduction in A1c reduces long-term microvascular complications by 20% to 32%.”

By slowing disease progression, the onset of complications can be delayed 15 to 20 years. And, Morello pointed out, keeping glycemic levels under control for several years continues to reduce future complications, even if the patient is unable to maintain glycemic control later in life.