Diabetes Forecast

Your A1C: Achieving Personal Blood Glucose Goals

By Erika Gebel, PhD

Things used to be so simple. Until the 1950s, insulin was the only diabetes medication. Today, insulin is still a must for people with type 1, but there are almost a dozen classes of medications for those with type 2 diabetes. So how do doctors and patients come up with a game plan to meet blood glucose goals? Well, it's personal. Experts now think that treatment should be tailored to the individual and that each type of diabetes medication has a place at the table.

Common Ground
There are two type 2 treatments that most diabetes experts agree on: lifestyle changes and metformin. Healthy eating, weight control, and exercise are tops for helping people control blood glucose. Metformin comes next; this inexpensive and time-tested drug is typically the first diabetes medication prescribed for people with type 2, unless there are specific health conditions that make using it dangerous. For example, metformin is not recommended for people with significant kidney disease or congestive heart failure.

If metformin can bring A1C (a measure of average blood glucose over the previous two to three months) down to a patient's target (see "What's Your Number?" below) and keep it there, then no further treatment is necessary. But if A1Cs creep up, as they often do, it's important to change something, says David Nathan, MD, director of the Diabetes Center at Massachusetts General Hospital. First, he says, you can gradually increase metformin until the maximum recommended dosage is reached, as long as gastrointestinal side effects don't become too much of a problem. "If A1Cs are not at goal three months later," Nathan says, "additional drugs are needed."

What's Your Number?
Just about everyone with diabetes used to be advised to reach a target A1C of less than 7 percent. In the past few years, though, things have changed. Now, evidence shows that some people can strive for even lower numbers, maybe 6 to 6.5 percent, while others can loosen their target to 7.5 to 8 percent. The American Diabetes Association recommends basing the tightness of the A1C goal on several criteria. First, life expectancy is a factor, because people expected to live just a few years may not have time to develop diabetes complications. They may want to ease up on their blood glucose control, while young, healthy people who haven't had diabetes long have the option of tightening up. Similarly, whether a person has other conditions, such as heart or kidney disease, can also help guide doctors and patients to an appropriate A1C goal. People at high risk for low blood glucose (hypoglycemia) may fare better with a less stringent goal. How long a person has had diabetes also plays a role, with stringent goals more suitable for the newly diagnosed than those who've had the disease for decades. Finally, more highly motivated people may be better candidates for a tight A1C target than those less interested in self-management.

Algorithm Debate
Only about 3 to 5 percent of people with type 2 diabetes see an endocrinologist, says Nathan, while the rest are treated by primary care physicians. In 2009, Nathan and a panel of diabetes experts published in the journal Diabetes Care a treatment "algorithm," a tool that helps doctors who are not diabetes experts select medications for patients with type 2. "We said 'these are our recommendations' in a fairly straightforward way," says Nathan.

The panel suggested that patients have an A1C test every three months. If the A1C is over a patient's goal and the maximum metformin dose has already been prescribed, the algorithm offers two primary options as a next step: long-acting insulin injections or sulfonylureas. The data show these are the best choices, says Nathan, because both insulin and sulfonylureas are older diabetes medications with a long history and well-known properties. If sulfonylureas don't work, then a switch to a metformin-plus-insulin regimen is suggested, starting with a long-acting insulin, then adding a mealtime insulin as necessary to meet A1C goals.

Other type 2 treatments are relegated to a second tier in the algorithm, to be considered under certain circumstances. "We did not recommend every drug that's been approved by the [Food and Drug Administration]," says Nathan, because the data just weren't there to support using the newer medications instead of the tried-and-true ones.

The "Me" in Treatment
In June 2012, the American Diabetes Association (ADA) and the leading European diabetes group issued an official position statement on treating high blood glucose in people with type 2. The central theme is that treatment strategies should focus on the patient. "This isn't a novel idea," says Silvio Inzucchi, MD, director of the Yale Diabetes Center and a co-chair of the group that wrote the statement. "We just tried to stress this notion more."

Questions to Answer
Here are examples of questions doctors and patients may want to consider when selecting medications for type 2 diabetes, plus information to weigh in answering those questions.
How much does A1C need to be lowered to get to goal?
Good to know: Metformin and sulfonylureas may lower A1C 1.5 to 2 percentage points, GLP-1 agonists and DPP-4 inhibitors 0.5 to 1 percentage point on average, and insulin as much as 6 points or more, depending on where you start. Individual results may vary.

How prone is the person to hypoglycemia?
Good to know: "For an older patient predisposed to low blood glucose, you wouldn't want to choose strategies that lead to low blood glucose," says Silvio Inzucchi, MD, of Yale University. Metformin, DPP-4 inhibitors, GLP-1 agonists, and medications known as "glitazones" do not cause hypoglycemia.

Would weight loss be desirable, or would weight gain be unacceptable?
Good to know: A GLP-1 agonist may result in weight loss; insulin can be linked with weight gain if too many calories are eaten.

What types of side effects are tolerable?
Good to know: Up to 20 percent of people who try metformin give it up because of side effects including diarrhea, nausea, and vomiting. DPP-4 inhibitors seem to have less side effects, and in fewer people.

How much does the medication cost, and is it affordable?
Good to know: Some medications, such as sulfonylureas, are available in inexpensive generic forms, while GLP-1 agonists can cost hundreds of dollars a month and may not be covered by insurance.

The ADA's position is that, as with the algorithm, lifestyle changes and metformin are first in line. "We felt that while we could all agree on what to do at step A, beyond that there are really five choices that are credible," Inzucchi says. "Based on the evidence, you can't pick one versus the other." Rather than a road map offering only two routes, insulin or sulfonylureas, the statement suggests adding to metformin any one of the other five major classes of type 2 medications—sulfonylureas, thiazolidinediones ("glitazones"), DPP-4 inhibitors, GLP-1 agonists, and insulin—to get control. Each has unique characteristics, and the statement breaks down the medications' properties as they relate to effectiveness, the risk of hypoglycemia (low blood glucose), weight, side effects, and cost. The doctor and patient are meant to make a decision based on these factors (see "Questions to Answer," right).

Like the algorithm, the statement recommends A1C tests every three months. If goals aren't met with a two-medication combination (metformin plus one of the five other types of drugs), the recommendation is to proceed to a three-drug combo, while still considering the patient's characteristics and desires. Most of the diabetes drugs can work together, but the statement recommends against combining a DPP-4 inhibitor, such as the oral med sitagliptin (Januvia), and a GLP-1 agonist, such as the injectable drug exenatide (Byetta), because they work via a similar mechanism. It also says to avoid using insulin with a sulfonylurea, as the oral medication wouldn't increase effectiveness. If a strategy that includes a long-acting insulin doesn't bring glucose levels down in three to six months, the statement recommends a move to add mealtime insulin

"People are going to have different approaches," says Inzucchi, and so it's important not to exclude approved treatment options that could become part of a patient's perfect recipe for health.



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