1 June 2011

Many people with type 2 diabetes can manage blood sugar levels effectively on oral diabetes medications and lifestyle changes alone. Others will need to combine oral diabetes medications with injectable diabetes drugs in order to bring their blood glucose levels into a healthy range. Finding the right combination is the key to managing diabetes successfully.

For years, insulin was the only injectable diabetes medication available to help control blood sugar. Today, several newly approved injectable diabetes drugs are available. A growing number of medication options are also available, so doctors can individualize diabetes treatment with greater precision than ever before.

Combining Diabetes Medications for Optimal Effect

How will your doctor decide the best diabetes drug regimen for you? “The first principle is to make life as easy and therapy as effective as possible,” says Daniel Einhorn, MD, president of the American Association of Clinical Endocrinologists and medical director of the Scripps Whittier Diabetes Institute in La Jolla, Calif. “Type 2 diabetes is a lifelong problem. We want to choose therapies that people can easily live with.”

One factor is how comfortable people feel giving themselves injections. “Some patients are fine with injectable medications. Others will do anything not to have to give themselves injections,” says Eleftheria Maratos-Flier, MD, professor of medicine at Beth Israel Deaconess Medical Center in Boston.

The second principle of combination diabetes drug therapy, according to Einhorn, is choosing medication therapies that work in complementary ways. “Today we have a variety of drugs that work in very different ways, so combinations can be especially effective,” says Einhorn.

One of the most commonly used oral drugs, metformin (sold under the brand names Blumetza, Fortamet, Glucophage, and Riomet), is considered the cornerstone of most combination therapy. It works by decreasing the amount of glucose produced by the liver. Metformin can be paired with insulin or with a GLP-1 agonist, which stimulates insulin production.

Doctors may also combine insulin with a GLP-1 agonist and a thiazolidinedione oral medication  (Actos and Avandia), which sensitizes the body to insulin. For people comfortable with using injectable drugs, doctors may recommend one of the two new GLP-1 agonists, Byetta and Victoza.  For people who don’t want an injectable drug, the alternative is a DPP-4 inhibitor (Januvia and Onglyza), which is taken orally. Both of these classes of drugs work in a similar way and are considered equivalent.
Weighing the Pros and Cons of Drug Combinations

Minimizing adverse effects is also important. Some diabetes medications can cause blood sugar levels to drop too low, causing hypoglycemia. The oral medication sulfonylurea (DiaBeta, Glynase, Micronase), which has long been used for type 2 diabetes, poses a moderate risk of causing hypoglycemia. Many doctors prefer to prescribe metformin, which is much less likely to cause hypoglycemia. Metformin is often paired with a GLP-1 agonist because these new injectable drugs work only when blood sugar levels are high, further avoiding  hypoglycemia.

Weighing the Pros and Cons of Drug Combinations continued…

Body weight is another issue doctors consider in choosing a combination diabetes therapy. Many people with type 2 diabetes are overweight or obese. Excess body weight worsens blood sugar control. Unfortunately, some oral agents, such as Actos and Avandia, tend to cause weight gain. Insulin also tends to promote weight gain.

“Since being weight increases diabetes risk and poses other health problems, we want to try to choose medications that help people maintain a healthy weight whenever possible,” says Einhorn. The first choice for oral diabetes medication is typically metformin, which does not promote weight gain. In overweight or obese patients, it is often paired with a GLP-1 agonist. These new agents have been shown to suppress appetite and increase satiety, helping roughly 30% of patients on them to lose modest amounts of weight.

Almost all drugs have unwanted side effects in some people, of course. Metformin can cause nausea, abdominal pain, and diarrhea in a very small percentage of patients. GLP-1 agonists can also cause gastrointestinal side effects. “We do have a small percentage of patients who go off them because they just can’t tolerate the side effects,” says Marina Basina, MD, clinical assistant professor of medicine in the division of endocrinology at Stanford University in Stanford, Calif. “But most patients do well on them.”

Patients who can’t tolerate GLP-1 agonists may fare better on another new injectable diabetes drug, called pramlintide (Symlin). A synthetic form of a naturally occurring hormone that helps the body maintain normal blood sugar levels, pramlintide is approved for use when insulin alone does not adequately lower blood glucose levels.
A Matter of Trial and Error

Choosing the best diabetes therapies is as much an art as a science. The American Diabetes Association publishes annual treatment guidelines. Leading professional groups also release recommendations. “But the field of diabetes treatment is changing so fast that some guidelines may be out-of-date almost as soon as they’re published,” says Maratos-Flier. “The only way to find the best therapeutic regimen is through trial and error. There’s almost no way to know in advance how patients will respond to a given medication or combination of medications.”

What’s more, drug regimens must be tailored to the individual patient. “There is no single best combination for all patients,” says Basina. “And over time, we often have to change the regimen if patients stop responding to a certain drug or develop side effects.”

To make sure your diabetes medication regimen is working adequately, it’s important to monitor blood sugar levels. How often you test blood sugar levels will depend on the medications you’re taking and how well your blood sugar levels are controlled.

“The sooner you bring blood sugar levels down to normal, and the better control you have over time, the less likely your diabetes is to progress,” says Einhorn.

This article was published in www.webmd.com on 3 April 2011.