The 21st century may be remembered as the time when diabetes became a worldwide epidemic. However, it may also be known as the time when the disease was cured.
Currently, new type 2 diabetes treatments are coming to market every six to nine months. With so many new treatment options on the market, things are quickly getting quite confused. How should a diabetes patient evaluate which therapy is best? Endocrinologists suggest a cautious approach. “We’ve got some good agents already on the market. So whatever you’re starting needs to have more benefit than anything that’s currently available,” says Athena Philis-Tsimikas, MD, executive director of the Whittier Institute for Diabetes, of San Diego, Calif. The institute is a subsidiary of Scripps Health.
“I’ll be the first to admit that I’m relatively conservative about using new drugs,” says Jonathan R. Anolik, MD, chief of the endocrinology section at Virtua Memorial Hospital, in Mt. Holly, N.J. “When you have an old drug that has good tolerability, works well, and has good outcomes data associated with it, then it makes sense to use an old drug before a new drug.”
The biggest disadvantage to the new treatments is their cost. All of the new drugs coming to market are entering at a premium price point. “Insurance companies can be charging anywhere from $20 to $40 per prescription in co-payments,” says Tsimikas. “But the costs of the actual agents to the insurance plan are large as well, and those costs will eventually get transferred to the patients. There’s no getting around that. It might not be a direct cost, but it will eventually contribute to what the health plan charges.”
Nevertheless, a great many endocrinologists are finding that the benefits of diabetes treatments that have come to market in the past few years are worth evaluating.
Byetta: The New Gold Standard?
For the type 2 diabetic, the most important new drug to come to market is very likely Byetta (exenatide), which is manufactured and marketed by Eli Lilly & Co. and Amylin Pharmaceuticals Inc. Byetta is the first entrant into the market of a new type of drug called an incretin mimetic. Approved for market by the U.S. Food and Drug Administration in April, 2005, Byetta is a synthetic hormone that lowers blood sugar and, in many cases, also causes patients to lose weight.
It is this combination of blood sugar control and weight loss that has made quite a few endocrinologists consider Byetta to be the new gold standard of type 2 treatment. “Byetta improves blood glucose and does not have hypoglycemia associated with it,” says Tsimikas. “It causes weight loss instead of weight gain. It’s not even weight neutral.”
However, the new drug is not without its limitations. Not only is it necessary to inject Byetta twice daily, but it can also cause nausea when patients first begin using it. “I think Byetta is the most significant of the new drugs,” says Leann Olansky, MD, a clinical endocrinologist at the Cleveland Clinic, in Cleveland, Ohio. “But it’s not very convenient, because it has to be injected twice a day.”
A long-acting version of the drug that would only require injections once a week is currently being evaluated and may be available in 2008. In fact, some specialists think the long-acting version may work better than the twice-daily formulation because it will sustain a more consistent level of the drug in the blood throughout the day.
Januvia Provides Oral Blood Sugar Control But No Weight Loss
On the other hand, another drug recently debuted that is neither injected nor prone to cause nausea. Januvia (sitagliptin) is a new oral, anti-diabetic drug that is manufactured and marketed by Merck & Co. Inc. It received FDA market clearance in October 2006 and is also widely available internationally. Januvia is the first of a new class of drugs called dipeptidyl peptidase-4 inhibitors, or DPP-4s. “Januvia seems to have very little if any side effects,” said Olansky. “It’s a pill that you take once a day. You don’t have to think about it.”
In some ways, Januvia’s mode of action is a little bit like Byetta, but instead of adding a hormone to the bloodstream, it blocks the breakdown of that hormone. The result is that, like Byetta, Januvia helps to control the blood sugar. However, it does not cause a patient to lose weight. In some cases, Januvia may be an attractive alternative for recently diagnosed diabetics who would otherwise receive a sulfonylurea. “Theoretically, Januvia would be a much better choice than the sulfonylurea agents that we currently use because it doesn’t cause hypoglycemia, whereas sulfonylureas can,” says Tsimikas.
Byetta is typically prescribed for patients who have already failed to obtain effective blood sugar control on at least one or two other oral diabetes drugs. However, some specialists prescribe the drug earlier, especially when weight loss is important. It is usually given in combination with other oral diabetes medications, or even with insulin, in some cases.
Januvia is indicated for use earlier. However, some specialists say that newly diagnosed patients have had difficulty getting the drug covered by their insurance. “Even though the FDA approved Januvia to be used as initial therapy in a brand new diabetic, the insurers are not anxious to pay for that,” says Olansky. “They want people to be on at least one other oral agent and to add Januvia if the one agent is not controlling them sufficiently.”
In March, the FDA approved another Merck drug, called Janumet, which is a combination of Januvia and metformin in one pill. Specialists say the new formulation could be more convenient for patients needing to add Januvia to their existing metformin prescription because only one co-payment would be necessary to fill the prescriptions. However, unlike Januvia, which is taken once a day, Janumet is taken twice daily.
The future of diabetes treatment has many in the endocrinology community optimistic about the future. However, the best treatment option continues to be avoiding diabetes onset through diet and exercise. “It’s exciting that we have all these new medications that allow us to control the blood sugars in effective ways without the weight gain or hypoglycemia,” says Tsimikas. “But what would be more exciting would be to get the message across that lifestyle changes and other methods of weight control and dietary habits are what we need for the long term.”
Athena Philis-Tsimikas, MD, Whittier Institute for Diabetes
Jonathan R. Anolik, MD, Endocrine Associates of South Jersey
Leann Olansky, MD, Cleveland Clinic