Novartis SA reports the U.S. FDA has demanded additional data, including a clinical study in patients with kidney impairment, before giving Galvus its approval. Why the holdup?

The FDA wants more data studying Galvus in patients with impaired kidneys. It had been thought that Galvus might have an advantage because it is not processed by the kidneys, while Januvia is. But another molecule created when the body metabolizes Galvus does build up in the kidney.

In the Feb. 1 issue of The New England Journal of Medicine, David M. Nathan, a Harvard Medical School endocrinologist, noted that it was surprising that the FDA decided to clear Januvia at all, given the "paucity of published data from long-term clinical trials on its safety and efficacy." Nathan is a consultant for Novartis and other drug makers but not Merck.

There are several potential concerns about DPP-4 drugs, clear evidence has not turned up in clinical trials so far. The medicines could affect the immune system, because a receptor on immune cells is very similar to DPP-4. Merck says that Januvia was designed to bind only to the DPP-4 enzyme, reducing the chances of these side effects. Patients with impaired kidneys have more of the drug in their bloodstream and would be more likely to experience side effects.

A small molecule has been identified that controls diabetes in mice and may pave the way to the development of easier treatment for adult-onset diabetes.

This key molecule, called Boc5, can stimulate insulin function and reduce body weight by 20%. The molecule stimulates the production of the glucagon-like peptide1 (GLP1), responsible for metabolizing glucose. The study intended to discover ways to sensitize insulin by stimulating production of GLP1. Boc5 is not powerful enough to become a diabetes or weight loss drug. But researchers suggest that similar compounds could join the latest generation of diabetes drugs, called "incretin mimetics." The first FDA-approved incretin mimetic was Byetta. A second such drug, with the generic name liraglutide, is in clinical trials.

The problem with the existing FDA approved incretin mimetic treatments is that they are large molecules that must be administered through injection. Boc5 is a small fry with big potential. Being a smaller molecule gives hope for a new generation in diabetes treatment in the form of a pill many of us would be happy to swallow.

On Tuesday, October 17, the clouds parted and the medicinal gatekeepers welcomed the birth of a little bundle of joy from Merck & Co, named Januvia. Weighing in at $4.86 per tablet, and guaranteed to control blood sugars without the undesirable side effect of weight gain, Merck said Januvia would be in pharmacies in the near future.

This is a new class of pills called DPP-4, or dipeptidyl peptidase IV. These are inhibitors that work to enhance the body's own ability to lower blood sugar. In clinical trials, patients did not gain weight. Yippee! Taken once a day, Januvia is expected to face competition from Novartis AG's rival medicine Galvus, which is awaiting FDA approval, possibly next month. The first generation of drugs designed to combat insulin resistance notoriously caused water retention and gain weight.

The empirical evidence is shining through already. A survey of about 60 physicians, conducted by Reuters Primary Research, shows the vast majority of doctors intend to start prescribing Januvia and Galvus right away. Dr. Stuart Weiss, a New York University Medical Center endocrinologist, said the drug's ability to control blood sugar spikes without added weight gain was a big draw. "In the face of a diabetes epidemic, this drug ... is particularly an inviting choice," said Weiss, who has consulted for several Merck competitors, including Novartis. If the near $5 a day price tag doesn't send your budget into a tailspin, you might have the shelf space for a DPP-4 in your near future. Praise be the DPP, for the sugars will come down and the scales won't creep up!