American Diabetes Association (ADA): round up

Related tags Diabetes Insulin Diabetes mellitus

The latest research included in the proceedings of the annual
scientific meeting of the American Diabetes Association (ADA) means
that diabetic treatments and other therapies for the disease
feature strongly in DrugResearcher's periodic round-up of new
compounds entering the clinic.

Swiss pharmaceutical firm, Novartis, demonstrated in clinical studies that its investigational drug vildagliptin improves the function of pancreatic islets in both animals and humans.

Vildagliptin, a novel investigational Incretin Enhancer, 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.

"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,"​ commented Ameet Nathwani, vice president, cardiovascular and metabolism at Novartis.

"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,"​ he added.

Diabetes has become a disease of epidemic proportions, affecting more than 20 million Americans and approximately 194 million worldwide. Despite the proliferation of many new, novel treatment options, the disease remains poorly controlled and the majority of people with Type 2 diabetes have not achieved the goals for blood glucose levels and are at risk for serious health complications

The first in a new class of therapeutic agents called selective CB1 Blockers was the subject of a Phase III study in which rimonabant, was shown to significantly improve HbA1c (a measure of blood sugar control), dyslipidemia (abnormal levels of fat in the blood), and systolic blood pressure.

By selectively blocking CB1 receptors both centrally and peripherally in fat cells and liver cells, rimonabant helped to normalise an overactive endocrine system. The RIO-Diabetes trial was sponsored by Sanofi-Aventis.

The RIO-Diabetes trial results indicated that rimonabant delivered a reduction in HbA1c and I set to offer a broad range of cardiometabolic risk factor improvements that are essential for the comprehensive management of people with type 2 diabetes.

The ADA was an opportunity for the launch of a novel compound that provides long-term lowering of blood glucose levels and improves plasma lipids (fats) - all in a once-daily pill.

Muraglitazar targets the peroxisome proliferator-activated receptors (PPARs). Activator drugs such as muraglitazar are "keys" that fit into receptor "locks," changing cell function. Activator drugs that target PPAR-gamma (the glitazones), which is associated with improvements in insulin sensitivity and glycaemic control, have long been successfully used to treat type 2 diabetes.

Muraglitazar targets PPAR-gamma as well as PPAR-alpha, which is associated with regulation of lipids (blood fats). As a dual PPAR activator, muraglitazar becomes the first of a novel "glitazar" class.

What is unique about Muraglitazar is that it achieved these goals with only one pill a day, making it easier for people with type 2 diabetes to manage multiple health problems and may enhance patient compliance.

Entelos, a company involved biosimulation technologies for pharmaceutical research and development took the opportunity to present data describing the results of time-dependent effects of treatment in the non-obese diabetic (NOD) mouse, the most common animal model of human type 1 diabetes.

The second presentation described the Type 1 Diabetes PhysioLab platform, a large- scale mathematical model of diabetes pathogenesis and intervention in the NOD mouse.

The platform focuses on islet Beta cell autoimmunity and tolerance and related mechanisms and interventions. The virtual diabetic mouse exhibits characteristic insulitis in the islets and develops diabetes after twelve weeks of age if untreated. A number of interventions that were developed using the NOD mouse are also represented in the PhysioLab platform.

Research using this platform will help define the mechanisms driving pathogenesis in the NOD mouse and how differences between mouse and human biology may lead to differences in therapeutic response.

"Despite the success of numerous therapies in the NOD mouse, translational efforts to prevent or treat the human disease have been disappointing,"​ said Mikhail Gishizky, chief scientific officer of Entelos.

"We developed this model in collaboration with the American Diabetes Association to advance our understanding of type 1 diabetes pathogenesis using predictive mathematical models, and improve the rationale for advancing potential therapies into human clinical trials,"​ he added.

Finally, Lilly​ launched its Byetta (exenatide) treatment for type 2 diabetes patients unable to control disease with common oral therapies. This newly approved first-in-class treatment. Byetta belongs to a class of diabetes treatment called incretin mimetics.

By mimicking the mechanisms of a naturally occurring human hormone. Byetta is a diabetes self regulating drug that stays in the blood system, working actively only when blood sugar levels are too high. In clinical trials, Byetta was shown to help patients regulate blood sugar levels. Most patients in the long-term Byetta clinical studies also experienced reductions in weight.

Byetta exhibits many of the same effects as the human incretin hormone glucagon-like peptide-1 (GLP-1). GLP-1, secreted in response to food intake, has multiple effects on the intestine, liver, pancreas and brain that work in concert to improve blood sugar.

Byetta was approved by the FDA for use by people with type 2 diabetes who are unsuccessful at controlling their blood sugar levels despite using the commonly prescribed oral medications metformin, a sulfonylurea, or both.

An incretin mimetic works to mimic the anti-diabetic or glucose-lowering actions of naturally occurring human hormones called incretins.

These actions include stimulating the body's ability to produce insulin in response to elevated levels of blood sugar, inhibiting the release of a hormone called glucagon following meals, slowing the rate at which nutrients are absorbed into the bloodstream and reducing food intake.

"For a disease where more than two-thirds of the patients aren't achieving their target blood sugar levels, the availability of Byetta is a remarkable advancement for the diabetes medical community. Byetta addresses a core defect of type 2 diabetes, where the body fails to respond normally to food intake, causing blood sugar levels to rise and fluctuate in an unhealthy manner,"​ said Dr Carol Wysham, clinical endocrinologist at Rockwood Clinic in Spokane, Washington.

Related topics Preclinical Research

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