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Medications: Edging Closer to a Cure

Diabetes drugs help to manage the body’s constantly fluctuating levels of blood glucose. But a healthy biochemical balance of the hormones involved in that process—insulin, incretins and more—is painfully delicate. Diabetes medications have consequently often had side effects that were unpleasant (such as weight gain) and, in a few cases, even dangerous. Witness Avandia, a popular drug available since 1999 that lowers blood glucose by making cells more receptive to insulin—but that also, according to a report published in the New England Journal of Medicine in May, increases the risk of heart attack.

Which is why the next generation of drugs has doctors so hopeful. By targeting different hormones that help the body manage its own insulin levels—and by reducing side effects such as weight gain—three drugs recently approved by the FDA avoid most of the major problems associated with past diabetes treatments. The drugs are not a replacement for insulin, but they do more than any drug in the past to assist the body in making its own. And although they may represent only another small step toward a “cure” for diabetes, they are beginning to provide patients with levels of control never before seen over their own hormones.

Byetta (exenatide), for example, made by Eli Lilly and Amylin Pharmaceuticals and approved by the FDA in 2005, mimics a hormone, incretin, that stimulates the pancreas to produce insulin in response to elevated blood glucose—something healthy pancreases do naturally. The injectable drug was inspired by the digestive system of the Gila monster, which needs to eat only three or four times a year; a chemical compound in the lizard’s saliva called exendin-4 seems to jump-start its pancreas after its multimonth fasts. Exenatide, which is derived from that same compound, increases the insulin produced in response to meals and slows the absorption of carbohydrates in humans. Byetta therefore not only helps patients with type 2 diabetes control their glucose levels, but it also reduces appetite, leading to weight loss.

Another drug made by Amylin Pharmaceuticals and approved by the FDA in 2005, Symlin (pramlintide), has a similar effect. Symlin, which is for both type 1 and 2 diabetes, simulates a different hormone, amylin, which is secreted by the pancreas along with insulin after meals. Often referred to as a satiety hormone, amylin makes the body feel full by slowing the rate at which food passes from the stomach to the intestines. On average, people taking injections of Symlin ate significantly fewer calories per day, according to a study sponsored by the company. Losing weight can itself help improve diabetes. For both Byetta and Symlin, however, nausea is a significant side effect, so neither is a perfect therapy.

Then there is Januvia (sitagliptin phosphate) for type 2 diabetics, produced by Merck and approved in October 2006. An oral tablet taken once daily, Januvia is the first in a new line of pharmaceuticals that raise incretin levels in the body by inhibiting the production of DPP-4, an enzyme that naturally destroys incretins. Blocking DPP-4 also signals the liver to release less glucose into the blood, thereby lowering the body’s need to produce insulin. The drug also reduces weight gain.

A few potential complications are associated with all three new drugs. Delaying the emptying of the stomach, for example, can make timing insulin injections more difficult—and will certainly require more individualized dosing regimens. It also isn’t clear what Januvia’s effects on breaking down hormones, in particular, will have on long-term toxicity levels in the body. Some doctors still hesitate to prescribe it for this reason. —Justin Ewers

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