New Drug May Someday Battle Obesity and Diabetes – WebMD

New Drug May Someday Battle Obesity and Diabetes

Researchers find slim evidence to support many

By Dennis Thompson

HealthDay Reporter

WEDNESDAY, Oct. 30 (HealthDay News) — A new diabetes drug may one day perform double duty for patients, controlling both their blood sugar levels and helping them lose weight, researchers report.

In mouse trials, doctors found the drug prompted weight loss, in addition to managing blood sugar levels.

“That [weight loss] is not what this drug was designed to do, but it’s a very attractive additional benefit,” said study co-author Richard DiMarchi, a research chemist at Indiana University in whose lab the drug was created.

The injectable medication is based on a single molecule that combines the properties of two hormones that send chemical signals to the pancreas, said DiMarchi.

“They signal to the pancreas that you are taking a meal,” DiMarchi said. “The pancreas then responds by secreting insulin and to synthesize additional amounts of insulin for subsequent use.”

People with type 2 diabetes have lower levels of these pancreas-signaling hormones, which are known as incretins, explained Dr. John Anderson, president of medicine and science at the American Diabetes Association.

“The incretin defect in type 2 diabetes is well known, and it’s only within the last few years we have had agents to treat it,” Anderson said.

Human and primate trials revealed that the new drug controls blood sugar with fewer side effects than other diabetes medications. Those side effects can include nausea, vomiting and stomach pain.

“In this study, the degree of gastrointestinal discomfort is much more modest than is experienced in conventional drugs,” DiMarchi said. “We get beneficial glycemic control with this combination drug, and it seems to be with less adverse drug effect.”

The medication combines the action of the hormones GLP-1 and GIP. Current diabetes medications of this sort target GLP-1 receptors in the body; studies involving GIP have produced mixed results.

GLP is known to suppress appetite, and DiMarchi said the weight loss observed in mice might be occurring because the second hormone, GIP, is somehow “turbo-charging” that appetite suppression.

In the mouse trials, a drug based on GLP-1 alone decreased body weight by an average 15 percent. But the new drug combining GLP-1 and GIP decreased body weight by nearly 21 percent, as well as controlling blood glucose and decreasing appetite.

A six-week human trial involving 53 patients with type 2 diabetes found that the medication effectively controlled their blood sugar levels. However, the researchers did not note any change in weight during the relatively short study period.

The higher potency of the combined molecule suggests it could be administered at lower doses than other incretin-based medications, reducing side effects and making the drug easier to take.

“Currently approved drugs are quite effective,” DiMarchi said, “but they are insufficient in normalizing glucose, and they certainly don’t cause much loss of body weight.”

Merck's $5.7 Billion Diabetes Franchise Vulnerable

A retrospective analysis published by the BMJ supports previously published findings that diabetic patients taking drugs which target the incretin system to control their blood sugars are at greater risk for developing pancreatic problems, such as acute pancreatitis and pancreatic cancer. Could certain big pharma manufacturers be vulnerable to a price collapse, should European and U.S. regulators – whom are now actively reviewing data on adverse events – move to restrict usage or outright remove these therapies from the market due to questionable safety?

MRK Total Return Price Chart

MRK Total Return Price data by YCharts

Incretin-based therapies, such as GLP-1 agonists and dipeptidylpeptidase-4 (DDP-4) inhibitors, mimic the glucose regulating role of intestinal hormones. As they carry a lower risk of hypoglycemia and have observed weight-loss properties, the two drug classes have readily been adopted by physicians for treating type-2 diabetes, with several drugs rapidly growing annual sales in the estimated $40 billion market for diabetes control medications.

MRK Revenue Annual Chart

MRK Revenue Annual data by YCharts

As Merck (MRK) looks to reset its revenue base due to patent losses, its DDP-4 inhibitor, Januvia (sitagliptin), remains critical to its financial health. In FY 2012, global sales of the combined diabetes franchise of Januvia/Janumet (which contains the popular type-2 diabetes drug metformin) grew 23% to $5.7 billion, primarily driven by growth in the United States and Japan. A global ban would wipe out more than 12% of the drug maker’s annual sales!

Though Novartis’ (NVS) DDP-V inhibitor Galvus delivered 34% growth in 2012, its $910 million in sales accounted for less than 2% of the $57 billion in annual drug sales. The Swiss-based company’s growth engines are fueled by oncology and neuroscience drugs, such as Gleevec and Gilenya (multiple sclerosis).

The consumer advocacy group Public Citizen has petitioned the FDA to remove Novo Nordisk’s (NVO) Victoza (liraglutide). Albeit the Danish-based drug maker derives almost 10% of annual sales from this GLP-1 agonist, the current safety debate could actually benefit the company: Insulin products generated almost 60% of the $11.7 billion in drug revenue last year; and, with a global insulin market share of more than 47%, any move back to mainstream diabetic treatment would likely more than offset lost sales from Victoza.

In addition to lost sales, all drug makers of incretin mimetics, including the newer DPP-4 inhibitors – Tradjenta (linagliptin) from Eli Lilly (LLY) and Nesina (alogliptin) from Takeda – will need to put aside reserves due to the possibility of multi-million dollar injury settlements (class action lawsuits are being filed).

David J. Phillips, a contributing editor at YCharts, is a former equity analyst. His journalism has appeared in Bloomberg BusinessWeek, Forbes, and Kiplinger’s Personal Finance. From 2008 to 2011, David was a reporter for CBS News Interactive. He can be reached at editor@ycharts.com. You can also request a demonstration of YCharts Platinum.