If you’re diagnosed with type 2 diabetes, your doctor will probably advise you to lose weight, alter your diet, and take Metformin, a standard first-line diabetes medication. That’s the plan the American Diabetes Association recommends. But according to UNC diabetes expert John Buse, the plan is often not good enough, leaving doctors and patients to make an important decision.

“If those things don’t lower blood sugar enough, then there are five recommended second-line classes of drugs,” Buse says.

Click to read photo caption. Photo by: Donn Young

Inside each of those five classes are several different medications. Your doctor could choose any of them. The best doctors, Buse says, review the most current medical literature so they can parse the differences between diabetes medications and help patients make informed decisions.

As the director of UNC’s Diabetes Care Center, Buse helps with the parsing. He runs clinical trials to find out how diabetes medications stack up against each other.

 In 2008 and 2009, Buse led clinical trials that narrowed down the best courses of treatment within one drug class to daily shots of liraglutide or weekly shots of exenatide. Buse’s team then helped organize a head-to-head clinical trial of those two drugs. The researchers recruited 912 volunteers from 105 medical centers in 19 countries. Half of the patients received daily shots of liraglutide; half received weekly shots of exenatide.

Buse found that liraglutide was slightly better at lowering blood sugar and helping patients lose weight. But patients who took that drug were nearly twice as likely to experience side effects such as nausea, diarrhea, and vomiting.

So which is better? Buse says it depends on the patient.

“For some patients, the additional weight-loss advantage of liraglutide might tip the scales,” Buse says. Also, liraglutide is easier to use. It comes in a pen needle; patients simply flip off a cap, dial in the proper amount of the drug, and inject it into their leg or abdomen. “The needle is so fine that the shot is essentially painless,” Buse says. On the down side, you have to take liraglutide daily. Exenatide seems to work best when taken weekly.

“Frankly, taking something once a week can be a huge advantage,” Buse says. “For example, I have a cholesterol problem, and I have a really hard time remembering to take medication every day. I travel; sometimes I leave my pills at home.”

If you forgot to take liraglutide one day, Buse says, your blood sugar would likely spike within 24 hours and you might begin to feel symptoms—lethargy, frequent urination, blurred vision. If you travelled away from home without your pens, then you’d need to find yourself some liraglutide, toot sweet.

If you forgot to take a weekly injection of exenatide, there wouldn’t be any deleterious effects for days. That said, administering exenatide is a bit more involved. “It’s like a little chemistry kit,” Buse says. “You have to mix a powder with liquid. The needle is a bigger gauge—it’s wider—so the injection is less comfortable.” Some patients might consider all that a hassle, though Buse says the entire process takes only a minute or two.

Both drugs work very well, Buse says, and deciding which to take should be the result of a well-informed consultation between doctors and patients. Unfortunately, he says, such consultations don’t always occur because some doctors don’t delve terribly deep into the medical literature.

 “There are all kinds of very unscientific reasons why a doctor would prescribe one drug over another,” he says. A major reason is marketing—television spots, glossy magazine advertisements, drug company reps visiting doctors’ offices.

Buse says marketing campaigns must work to some extent or else drug companies wouldn’t spend millions of dollars on them. Sometimes, Buse says, a company will market a product that scientific studies have shown to be inferior—vildagliptin, for example. It’s a member of a class of diabetes drugs called DPP-4 inhibitors. Three other drugs in this class are available in the United States. Vildagliptin isn’t one of them. It has not been FDA approved, though it’s been approved for use in Europe.

“Vildagliptin is clearly the worst of the lot,” Buse says. “It has to be given twice a day, and there’ve been cases of liver toxicity.”

The other DPP-4 inhibitors are extremely well-tolerated, Buse says, and are good at controlling blood sugar. Yet, vildagliptin still rakes in the dollars overseas. The reason, according to Buse: the company that makes vildagliptin is very good at selling it. “At one level, it’s almost a scandal that marketing plays such a big role in who gets treated with what drug,” he says.

Another reason for the popularity of DPP-4 inhibitors is that they haven’t gone through head-to-head drug trials.

“Some companies would rather tough it out on marketing,” Buse says. “They know they won’t be able to demonstrate major differences on effectiveness.” But head-to-head clinical trials might, for instance, reveal that certain drugs cause more incidents of negative side effects—just what Buse found when comparing liraglutide and exenatide.

Only if you closely monitor the medical literature, or have a doctor who does, would you realize that not all drugs are created equal and maybe some shouldn’t be prescribed at all.

John Buse, a professor of medicine in UNC’s School of Medicine, directs UNC’s Diabetes Care Center, is chief of the med school’s Division of Endocrinology, executive associate dean of clinical research at Carolina, and a PI Extender of the UNC NIH Clinical and Translational Science Awards (CTSA). The studies mentioned in this article were funded by Eli Lilly and Company and Amylin Pharmaceuticals, which makes exenatide.