Diabetes News
EAST HANOVER, June 12 (PRNewswire-FirstCall) -- Research included in the proceedings of the annual scientific meeting of the American Diabetes Association suggests that the investigational drug vildagliptin improves the function of pancreatic islets in both animals and humans. Improved pancreatic islet function is a long-standing goal for the treatment of type 2 diabetes. Researchers also reported that vildagliptin, a novel investigational Incretin Enhancer, provides an effect equal to exendin-4, a recently approved injectable anti-diabetes drug, in improving measures of glycemic control and stimulating the growth of new insulin-producing beta cells in the islets of an animal model.
Vildagliptin, previously known as LAF237, inhibits an enzyme called DPP-4, resulting in an increase of circulating levels of GLP-1, a crucial incretin hormone. Incretin hormones are secreted from the intestines in response to a meal. GLP-1 stimulates the beta cells, located in the islets of the pancreas, to produce insulin, reducing the amount of glucose circulating in the body. GLP-1 also reduces the secretion of glucagon from the islets' alpha cells. People with type 2 diabetes also produce high levels of glucagon, signaling the liver to produce glucose. By restoring the production of insulin and suppressing elevated glucagon, vildagliptin improves glucose control mainly through improving pancreatic islet function.
Phase II study shows two key improvements: Greater beta cell function & improved insulin sensitivity
The Phase II study showed patients receiving oral vildagliptin and metformin for one year had improvements in how the beta cell functioned and experienced an increased sensitivity to insulin after eating a meal compared to those taking metformin alone. These effects were seen at 12 weeks and sustained for one year.
"For decades, researchers have been looking for compounds that can improve the way the pancreatic islets help regulate the glucose that the body needs to function," said Bo Ahren, M.D., professor, Lund University, Sweden.
The 52-week Phase II randomized, double-blind study involved 107 people with poorly controlled type 2 diabetes. In an earlier analysis of this study, patients in the vildagliptin + metformin group had a statistically significant reduction in fasting glucose levels and improved insulin secretion and sensitivity compared to patients taking metformin alone. Patients taking vildagliptin + metformin also experienced improved glycemic control for up to one year compared to patients who received metformin alone.
Phase III trials for vildagliptin are ongoing and are designed to evaluate the compound as monotherapy and in combination with other diabetes therapies.
Preclinical findings show that vildagliptin provides effect equal to Byetta(TM)
Novartis researchers presented data at the ADA answering a question many have posed about differences that may exist between the effects in animals of GLP-1 analogs, which are compounds that introduce additional GLP-1 into the circulatory system, versus the Incretin Enhancer vildagliptin, a therapy that prolongs the activity of the active GLP-1 already present in the system.
"Our team used a well-established animal model to observe the effect of both vildagliptin and the GLP-1 analog exendin-4 on beta cell neogenesis and blood glucose control, as measured by fasting blood glucose, total blood glucose and glucose tolerance," said Thomas Hughes, Ph.D., Head of Diabetes Research at the Novartis Institutes for BioMedical Research. "Both compounds had an equal effect on the development of new beta cells and both improved glycemic control. These results are significant since they suggest, in an animal model, that by enhancing the existing incretin hormones, versus introducing additional GLP-1, you may provide a clinically meaningful effect
in type 2 diabetes."
Exendin-4, an injectable GLP-1 analog, also called an Incretin Mimetic, was approved in April 2005 and is sold under the trade name, Byetta(TM). Vildagliptin is an oral medication being studied in Phase III trials.
Number of new beta cells nearly doubled when vildagliptin was introduced to animal model
In a second featured pre-clinical study, Novartis scientists demonstrated that enhancing the existing incretin system can lead to an increase in the number of newly formed beta cells. Increasing the number of beta cells has the potential to help people with type 2 diabetes since healthy beta cells are responsible for the production of insulin.
In a specialized animal model, designed to show rapid beta cell turnover and growth, vildagliptin treatment resulted in a decreased rate of beta cell death and increased beta cell replication, leading to a 40%-50% increase in the number of insulin-producing beta cells.
"The more we learn about vildagliptin, the more excited we are about its potential to change the way type 2 diabetes is understood and managed," said Ameet Nathwani, M.D., vice president, Cardiovascular and Metabolism. "Clearly, the drug's potential beneficial effect on the human incretin system is significant. Phase III trials are ongoing to determine how vildagliptin may fit into the pharmacological management of diabetes."
Diabetes affects about 170 million people worldwide and, according to the World Health Organization, that number will double to 366 million by 2030. The U.S. Centers for Disease Control estimates that 18 million Americans have diabetes, making it the sixth leading cause of death in the United States and a major contributor to heart disease, stroke, blindness, kidney disease and non-traumatic leg and foot amputations.
This release contains certain forward-looking statements relating to Novartis Pharmaceuticals Corporation's business, which can be identified by the use of forward-looking terminology such as "potential," "may offer," "may exist" or similar expressions, or by express or implied discussions regarding approvals to market vildagliptin. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the actual results with vildagliptin to be materially different from any future results, performance, or achievements expressed or implied by such statements. There can be no guarantee that vildagliptin will be approved for marketing or will reach any particular level of sales. Any such results can be affected by, among other things, competition in general; government, industry, and general public pricing pressures; unexpected clinical trial results; the company's ability to maintain patent or other proprietary intellectual property protection; as well as factors discussed in the Company's Form 20-F filed with the Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.
About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufacturers and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.
Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS) -- a world leader in pharmaceuticals and consumer health. In 2004, the Novartis Group's businesses achieved sales of USD 28.2 billion and pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 81,400 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.