Research 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 incretin enhancer, provides an effect equal to Exendin-4 ( Exenatide, Byetta ), 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. Patients 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.

A 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.

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.

Researchers assessed the 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, 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.
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, researchers 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 patients 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.

Source: Novartis, 2005


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