Two organizations offer key strategies for T2DM management

Late last year, the American Diabetes Association (ADA) released “2012 ADA/EASD Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach,” its updated position statement for the treatment of type 2 diabetes mellitus (T2DM), while the American Association of Clinical Endocrinologists (AACE) released its algorithm, “Comprehensive Diabetes Management Algorithm 2013 Consensus Statement,” earlier this year. Even though these two key sets of guidelines differ from each other, pharmacists can benefit from the recommendations presented in both publications.

The AACE algorithm

AACE’s algorithm (http://bit.ly/AACEalgorithm) is considered to be somewhat more prescriptive than ADA’s position statement, providing guidance on when practitioners should consider monotherapy, dual therapy, and triple therapy, based on A1c levels and symptoms.

“AACE intends for the algorithm to be as user-friendly as possible, since diabetes management is so complex and is a source of confusion for many,” said Devra Dang, PharmD, associate clinical professor, University of Connecticut School of Pharmacy.

In addition, for the first time, AACE looks beyond glycemic control and addresses diabetes prevention and management of dyslipidemia, and also compares the risks and benefits of all FDA-approved medications for T2DM, said Dr. George Grunberger, MD, FACP, owner of the Grunberger Diabetes Institute in Bloomfield Hills, Mich. Grunberger was a member of the AACE committee that developed the 2013 Consensus Statement.

 “We realize that type 2 diabetes care is so complex, and pharmacists and physicians need some help. We tried to be more prescriptive,” Grunberger said.

In AACE’s algorithm, drug therapy selection is stratified according to a patient’s baseline A1c. For patients with a baseline A1c between 6.5% and 7.5%, monotherapy (preferably with metformin) is recommended. Then, AACE recommends, dual therapy should be initiated when the baseline A1c is between 7.6% and 9%. Triple therapy or transition to insulin therapy is usually reserved for patients with a baseline A1c greater than 9%.

 “With the AACE algorithm, we acknowledge that you are who you are as you show up in the doctor’s office, and the management needs to be individualized accordingly. We look at the A1c you bring into the office as a principal guide to the initial choice of drug therapy,” Grunberger said. 

Visual aid

AACE’s algorithm includes an easy-to-understand graphic for glycemic control. In its “Glycemic Control Algorithm” chart, the importance of various therapies is represented by longer bars, and the color-coded bars let pharmacists and physicians also represent the safety and effectiveness of utilizing treatments and therapies.

“We created a decision tree that emphasizes safety and understanding of the risks vs. the benefits of the various drug classes. Hopefully, people can follow it and go from one area to the other to meet the individual's glycemic targets,” Grunberger said.

The Glycemic Control Algorithm chart stresses the importance of lifestyle modifications (including medically assisted weight loss), represented by the most prominent bar in the chart, topping any of the drugs. The color-coded bars let pharmacists and physicians know the relative safety of the numerous FDA-approved drugs for T2DM. Green represents medications and treatments that are relatively safer, and yellow represents therapies about which “there is some caution, and physicians should carefully consider the balance of risk versus benefit before recommending them,” Grunberger said.

For patients with an A1c of 7.5% or less, metformin is the top drug of choice, represented by the longest bar and the bar’s green coloring.

“However, quite a few patients cannot tolerate metformin or it is contraindicated for them, so we list other drugs logically suited for the individual patient. If the bar is shorter, but colored green, that means we think it is appropriate, but not as potent in its glycemic benefit as the drugs listed above that,” Grunberger said.

In reviewing all the FDA-approved drugs for T2DM, the AACE committee wanted to emphasize safety and help physicians and patients understand the risks versus the benefits of each drug.

”Certain drugs will have hypoglycemia or weight gain as a side effect. These issues are usually the two top concerns to both physicians and patients when it comes to intensification of therapy,” Grunberger said. 

Dang agreed that the 2013 AACE Consensus Statement is more detailed than previous AACE algorithms. “It provides detailed information on treating dyslipidemia, hypertension, and obesity, for example,” she said.

ADA/EASD position statement

Conversely, in terms of glycemic control, the ADA/EASD position statement (http://bit.ly/ADAstatement) is somewhat less prescriptive than the AACE algorithm.

“The ADA/EASD position statement doesn’t specifically indicate the order in which the different drugs should be used. After metformin, there is not a lot of guidance on which drugs should be used,” Grunberger said.

While the ADA/EASD position statement shies away from specific drug recommendations beyond metformin, “helpful clinical pearls are offered within the treatment algorithm for various scenarios,” said Stefanie Nigro, PharmD, assistant professor of pharmacy practice at Massachusetts College of Pharmacy and Health Sciences in Boston.

In addition, the ADA/EASD position statement focuses on decision-making that is shared by patients and providers.

“The authors state that patient preference, medication cost, and tolerability should be taken into consideration prior to initiating therapy,” Nigro said.

“They [ADA/EASD] emphasize that the decision should be patient-centered and keep in mind not only treatment effectiveness and safety, but also the patient’s wishes, quality of life, cost, and other factors,” Dang added.

In the ADA/EASD position statement, lifestyle modifications and metformin are suggested as initial therapy unless contraindications or intolerances exist.

“Metformin has a long-standing evidence base for efficacy and safety, is inexpensive, and may reduce risk of cardiovascular events. When metformin fails to achieve or maintain glycemic controls, another agent should be added,” the ADA wrote in its position statement.

Advancement to triple therapy or multiple daily insulin injections is reserved for patients who do not reach their respective goals despite dual therapy.  Medications with modest efficacy or intolerable side effects can be used when clinically appropriate, according to the ADA.

Policy shift

The ADA/EASD position statement has evolved significantly since ADA’s 2009 recommendations for the management of hyperglycemia. The 2009 algorithm recommended a three-step approach, Nigro said. Step 1 represented the initiation of lifestyle modifications and metformin at diagnosis. After two to three months, practitioners could initiate Step 2 by adding “well validated” therapies (i.e. basal insulin or sulfonylureas only).

After two to three months, if glycemic goals were not achieved, then “less validated therapies” could be considered as part of Step 3. In 2009, the “less validated” therapies included TZDs and GLP-1 agonists.

“At the time, less validated therapies did not have ‘sufficient clinical use to be confident regarding safety,’ according to the ADA,” Nigro said.

Conversely, the ADA/EASD 2012 position statement states that, essentially, any available FDA-approved agent can be used for care, according to Nigro.

“The position statement does a better job of weighing the pros and cons of each agent with respect to A1c-lowering ability, cost, hypoglycemia risk, and weight effects, to name a few. Selection [of treatments] is not based solely on A1c-lowering ability and evidence. Selection is now based on multiple factors, including patient preference,” Nigro said.

Data needed

Unfortunately, she added, owing to insufficient data, neither group offers recommendations for drug therapy based on A1c-lowering durability or beta-cell preservation ability.

The creators of the AACE algorithm recognize the challenges that come with more specific drug-therapy recommendations.

“The reason we provided an algorithm and not guidelines is because there are no head-to-head studies actually ranking these [DM] drugs against each other. What needs to be done is to have studies of these drugs, to be able to derive guideline-quality evidence from large, randomized clinical trials,” Grunberger said.

However, because the cost of conducting such studies is likely to amount to “hundreds of millions of dollars,” Grunberger does not anticipate that drug manufacturers and organizations will sponsor such tests.

“That’s the dilemma: No one is willing to fund these studies, and the current studies are all very limited in their scope. In that situation, it remains very difficult to have definitive pronouncements. The art of medicine and individualized approach to patients by experienced physicians are still required,” Grunberger said.

Similarities

Despite the previously noted differences between the ADA and AACE algorithms pertaining to glycemic control, there are several similarities worth noting.

“Both emphasize the importance of individualized patient-care planning, the need for early lifestyle interventions, and the use of metformin as a first-line treatment for type 2 diabetes,” Nigro said.

And use of both the AACE and ADA guidelines can greatly benefit physicians, pharmacists, and other healthcare practitioners.

“I teach both schools of thought regarding glycemic goals and the recommendations for treatment,” Nigro said. Ultimately, the primary care provider and medical team will set goals in collaboration with the patient, and patient-specific factors need to be taken into account, she added.

For example, older adults, those with increased risk or history of hypoglycemia, or those with advanced cardiovascular risk or cardiovascular disease are likely to need less stringent goals, according to Nigro.

“Therefore, perhaps the less-prescriptive ADA goals would be preferred. In younger, otherwise healthier patients (with no or few co-morbid conditions), the more stringent AACE goals may be preferred, since we know that tight glycemic control is associated with a reduction in microvascular end points,” she said.