Drug Topics - October 15, 2007 - (Page 5)

5 Saxagliptin, a DPP-4 inhibitor similar to ing the course of the trial. “If you calculate the sitagliptin (Januvia, Merck), is currently in amount of glucose loss that we’ve been seeing phase III trials for once-a-day administration, in the urine on a daily basis, it’s thermodynameither as monotherapy initial treatment for diically equivalent to about the same caloric loss abetes or in combination with metformin, thias if you spent 30 minutes a azolidinediones, or sulfonylurea. Fred day on an exercise bike,” exFiedorek, M.D., VP of cardiovascular and plained Fiedorek. Another immetabolic global clinical research, Bristol-My- Fred Fiedorek portant feature of da- “What we’re trying ers Squibb, said, “We’re going to be trying to says that pagliflozin, he said, is that it to do is develop understand whether it is different from treatments to does not depend on insulin itreverse diasitagliptin or not. The underlying expectation betes are still self. “So we’re excited about the treatments that will is that it will be similar in terms of overall ef- far off. possibilities of combining this allow patients to ficacy and safety profile.” medicine with existing diabetes mediExplaining why another DPP-4 could be useful, cines that do depend on either insulin have real choices to Fiedorek said, “There’s a large need for patients with release or insulin action.” treat their disease.” diabetes to have choices to treat their condition. The It’s too early to project FDA submismedicine they start with doesn’t necessarily work more sion or approval dates for dapagliflozin, Fred Fiedorek, M.D. than a couple of years. They need additional medicines but industry reports show approval Bristol-Myers Squibb to get under control.” possible in 2010. The goal, Fiedorek said, is to have data and be able to file for approval with the FDA the first half of 2008. Peering into the crystal ball If all goes well, the drug could be available to patients Scientists continue to work in the obesity area along in 2009. with diabetes control. “From a physiological perspective, there’s no question that they’re connected,” Moses •Dapagliflozin (trade name not yet announced), said. AstraZeneca and Bristol-Myers Squibb Added Fiedorek, “What we’re trying to do—all of Dapagliflozin is a new-mechanism drug called an us in pharmaceutical companies and biotech compaSGLT2 inhibitor, or sodium glucose co-transporter 2. nies—is develop treatments that will allow patients to It is being studied as a once-daily oral antidiabetic. Da- have real choices to treat their disease. [Pipeline] drugs pagliflozin allows the kidney to excrete glucose specif- are going to be pieces of the armamentarium that docically, so it comes out in the urine and is not reab- tors can use to treat diabetes. But treatment that will sorbed in the blood; thus, it does not contribute to the eventually reverse the disease completely is far off, I hyperglycemia that exists in diabetes. think.” Although glucose is normally filtered by the kidney, THE AUTHOR is a writer based in New Hampshire. nearly all of it is reabsorbed in the proximal tubule by SGLT2, which is located almost exclusively in the kidney. For patients with diabetes, retention of excess glucose by this pathway contributes to persistent high blood glucose levels. Research in animal models indicates that modifying this glucose absorption with SGLT2 inhibition reduces blood glucose independent of insulin secretion or action. “So we’re going to tell people that it’s beneficial to lose sugar in their urine with dapagliflozin,” Fiedorek said. “It’s actually the kidneys acting as a spigot or release valve for glucose.” Because glucose represents calories, its release through the kidneys may help to improve a diabetes patient’s problems with weight, Fiedorek added. “It’s actually causing patients to lose calories when that glucose is released,” said Fiedorek. Phase III trials, which are just beginning, will test not only improvements for blood sugar control but also participants’ weight dur-

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Drug Topics - October 15, 2007 Contents Drugs in the Pipeline for Diabetes Vanquishing Med Errors from Abbreviations What Pharmacy Schools Never Taught You The Week at a Glance What Kinds of Mistakes Do Pharmacists Make?

Drug Topics - October 15, 2007

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