GLIM PhyzioType^TM System: Glucose + Insulin Modulators

DIABETES + CVD, Reduction of Cardio-metabolic Risk by Glucose-lowering: Thiazolidinediones (TZDs) and Incretin Therapies

The GLIM PhyzioType System is currently in development. It will consist of 4 tests predicting blood glucose lowering efficacy (HbA1c), weight gain or loss, risk of edema, and likelihood of severe vomiting in response to TZD and incretin medications on a class-wide and drug-specific basis. A patent on the GLIM PhyzioType product is pending as an application.

A key component in the management of diabetes is control of blood glucose levels. Tight glycemic control can significantly reduce complications of type 2 diabetes mellitus, and guidelines issued by medical organizations consistently advise setting hemoglobin A1c (HbA1c) goals at 7%. By increasing peripheral insulin sensitivity, the thiazolidinedione (TZD) class of drugs. TZDs offer potentially comprehensive treatments of diabetes. However, TZDs have side effects of weight gain, fat accumulation and edema which worsen the diabetic and cardiovascular condition of the patient. Peripheral edema, advances in some cases to heart failure.

The most recent diabetes therapies are mimetics and enhancers of incretins. The incretins are enteric analogues of gut peptides augmenting the effect of orally ingested glucose in promoting insulin secretion. Exenatide, FDA-approved in 2005, reduces both blood sugar and HbA1c levels. Sitagliptin, FDA approved in 2006, extends the half life of the incretins leading to increased insulin secretion, inhibition of glucagon secretion, and delayed gastric emptying resulting in improved glycemic control.

As of now, the development of TZD side effects is unpredictable and potentially injurious to the patient, which discourages patient compliance and disrupts healthcare delivery. Such uncertainties burden medical management and increase healthcare costs. Black box warnings on the labels of pioglitazone and rosiglitazone were required by the FDA on August 2007 to alert the medical community to heart failure risk. According to the warning, patients should be observed carefully for signs and symptoms of heart failure, including excessive rapid weight gain, dyspnea, and edema. Furthermore the medications are contraindicated in advanced congestive heart failure.

The incretin therapies have side effects of severe nausea, vomiting, and acute pancreatitis. For sitagliptin the main clinical issue is highly variable efficacy and unpredictable potency, a concern in patients requiring tight glycemic control.

According to the American Diabetes Association (ADA), there are nearly 24 million children and adults in the U.S. with diabetes of which nearly 18 million have been diagnosed, most (90 to 95%) with Type 2 diabetes mellitus. The ADA also estimates that there are 54 million people that are pre- diabetic. Termed cardio-metabolic risk factors by the ADA, these can lead to serious cardiovascular disease. Sales of TZD and incretin therapies in the US exceed $6 Billion annually, reaching 10 million patients.