Incretin Hormones, a New Wave of Diabetes Research

Incretin hormones create a unique platform for new therapeutic options that improve pancreatic islet function, both short and long term, including insulin secretion by the beta cells and glucagon secretion by the alpha cells. A new understanding of specialized incretin – or gut –hormones may lead to significant advances in the treatment and management of type 2 diabetes.

Diabetes is a disease of epidemic proportions, affecting more than 20 million Americans. 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.

“While many different agents are available to treat type 2 diabetes, there remains a sea of unmet need for new and different therapies that will help us address the growing epidemic,” said Alan J. Garber, M.D., Ph.D., member of the AACE board of directors and Professor of Medicine at Baylor College of Medicine. “As endocrinologists, we’re excited about the unique mechanisms represented by the whole new area of incretin research.”

Recent advances in diabetes research have revealed the important role of incretin hormones, which are produced in the gastrointestinal tract, in maintaining glucose control. “We’re beginning to reshape our understanding of diabetes by moving beyond a solitary focus on insulin resistance,” said James Gavin, M.D. Ph.D., AACE member and Clinical Professor of Medicine at Emory University School of Medicine. “Today we have a new appreciation for the importance of pancreatic islet health and its essential role in achieving successful glucose control.”

Two novel incretin-based classes of investigational therapies – incretin mimetics and incretin enhancers – may offer new and additional benefits in the battle to achieve glucose control. Incretin mimetics are injectable products that mimic the effects of GLP-1, an incretin hormone. Byetta® (exendin-4), the first incretin mimetic, was approved by the FDA on April 29, 2005. Incretin enhancers are oral therapies that increase the level of incretin hormones naturally produced by the body. Several incretin enhancers are in various phases of clinical trials, including Vildagliptin (Novartis) and MK 431 (Merck).

“With the first incretin-based therapy, Byetta, approved last month, the era of advances that leverage the way incretins work has arrived,” said David D’Alessio, MD, Associate Professor of Medicine, University of Cincinnati. “Incretins are of great interest since we now know they play a central role in maintaining healthy blood sugar levels.”

Type 2 diabetes, also known as adult-onset or non-insulin-dependent diabetes (NIDDM), results when cells in the body no longer respond properly to insulin (insulin resistance) and/or the beta cells in the pancreas do not produce enough insulin. As a result, blood glucose levels rise to an unhealthy level. Type 2 diabetes occurs most frequently in adults, but is seen increasingly in adolescents as well.

Information about today’s “teach-in” program is available on www.aace.com. Presentations from the program will be posted on the site later this week.

This conclusion and other recent research were reported May 18, 2005 at the 14th Annual Meeting and Clinical Congress of the American Association for Clinical Endocrinologists (AACE) in Washington, DC.

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DID YOU KNOW:
Growth hormone has been touted as a good weight loss drug for the past 30 years. The doses used have left the recipients facially disfigured, thus limiting the usefulness of this process. The metabolic syndrome is usually present in diabetes 2, not infrequently in diabetes 1. It is associated with a decrease in growth hormone. The Journal of Clinical Endocrinology & Metabolism 2005 3; 90(3): 1466-74 reported a good decline in abdominal fat (brown fat) with smaller doses of the growth hormone that had been use before and by using it over a year. This had an additional result of decreasing insulin resistance, increased thigh muscle, reduced total and LDL cholesterol.