Leading experts, Anne L. Peters, MD, Ralph A. DeFronzo, MD, Alan J. Garber, MD, PhD, Robert R. Henry, MD, Richard Bergenstal, MD, and others, share their thoughts on GLP-1 therapy….
Dr. Carol Wysham, Clinical Assistant Professor of Medicine at the University of Washington and Clinical Endocrinologist at Rockwood Clinic in Spokane, Washington.
“In my experience, when I offer patients the options that are listed on the ADA Consensus Guidelines, they almost always gravitate to choices that are associated with lower risk for hypoglycemia and without the effects of weight gain. So almost all of my patients, when given the choice, are choosing to use incretin-based therapies because of the advantages they have with lack of hypoglycemia and weight gain.
GLP-1 and exenatide all correct each of those defects stimulating insulin secretion in a glucose-dependent fashion, and specifically, increasing the first-phase insulin response. They both decrease the abnormal glucagon secretion, resulting in decreased hepatic glucose output. They decrease gastric emptying, which in turn, decreases the rate of the delivery of nutrients into the intestine and slows the rise in glucose levels after a meal. Finally, they both have a central effect to decrease food intake.”
Anne L. Peters, MD, CDE, FACP, Professor at the Keck School of Medicine of the University of Southern California and Director of the USC Clinical Diabetes Program in Los Angeles, California
“I think that incretin-based therapies have really opened up a whole new avenue for treating diabetes; it’s a different mechanism. It’s a mechanism that is physiologic and really helps my patients be successful both in achieving their goals glycemically as well as in terms of weight. An area that we haven’t discussed is safety. At (a recent) ADA meeting, there were databases presented in which lots of patients were on varieties of drugs. There did not seem to be an increased risk for pancreatitis with exenatide, which has been a concern over the past couple of years. But I think that as exenatide and other GLP-1 agonists are used over time, we’ll get an increasing sense of their safety. Thus far it appears to me that the signals are on the positive side, meaning that these drugs seem to be pretty safe as we follow them over increasing amounts of time.”
Ralph A. DeFronzo, MD, Professor of Medicine, Chief of Diabetes Division, University of Texas Health Science Center at San Antonio, Staff Physician, Department of Medicine, Audie L. Murphy Division, South Texas Veterans Health Care System, San Antonio, Texas
“(A) major benefit of the GLP-1 receptor agonist, again exenatide, is the ability of this drug to bind to certain receptors in the appetite-regulating centers in the hypothalamus and the hindbrain to decrease appetite. Not surprisingly, this central mechanism of action is associated with significant weight declines in our diabetic patients. In association with the decline in weight, it is very common to see an improvement in the blood pressure and an improvement in the plasma lipid profile.We also know that the GLP-1 analogs on a long-term basis will preserve beta-cell function. An additional benefit of the GLP-1 analogs is that they delay gastric emptying, slowing the entry of carbohydrate into the systemic circulation from the gastrointestinal tract and thereby decreasing the rise in postprandial glucose.”
Q: Why is it that exenatide once weekly is more effective than exenatide BID?
A: Exenatide once weekly provides a sustained, constant, day-long pharmacologic elevation in the plasma exenatide concentration. Exenatide twice daily gives a peak plasma level followed by a nadir twice daily (ie, with breakfast and dinner). This leaves the lunch meal uncovered and provides no coverage during the overnight sleeping hours.
“Ask the Faculty: The Expanding Role of GLP-1 Analogs in the Management of Diabetes: A Clinical Update From Orlando.” http://www.peerviewpress.com/medical/online_projects/PVI/s171/facultyFAQ.php
Alan J. Garber, MD, PhD, Professor, Departments of Medicine, Biochemistry & Molecular Biology, and Molecular & Cellular Biology, Baylor College of Medicine, Houston, Texas
“These agents have the potential to change the diabetes treatment paradigm by replacing traditional secretagogues because of superior control, freedom from hypoglycemia, and association with weight loss. They will undoubtedly be used as a second- or third-line therapy in some and perhaps as first-line therapy for others in whom other conventional agents are poorly tolerated or for whom weight loss is more highly prized.”
Robert R. Henry, MD, Professor of Medicine, University of California, San Diego, and a Staff Physician in the Division of Endocrinology at UC Medical Center in La Jolla, California
“These are obviously very interesting compounds with wonderful potential not only to reduce glucose levels, but to reduce body weight, and they are simple to use. I was making it clear that now we’re talking about injections once a day or once a week, and again there is no risk for hypoglycemia when given alone, which is an important issue. We’ve got a very important class of compounds that are rapidly developing with many new compounds about to enter into the therapeutic arena.”
Richard Bergenstal, MD, President for Medicine and Science, ADA; Executive Director of the International Diabetes Center at Park Nicollet; and Clinical Professor for the Department of Medicine at the University of Minnesota
Regarding trial of Liraglutide vs Sitagliptin when added to Metformin: “The first thing to take away is that both did a good fairly good job at that goal: reduce A1c, minimize hypoglycemia, and minimize weight gain. If you need a little further drop in A1c to get to goal, you’re probably going to benefit by going with the GLP-1 agonist, with Liraglutide. If weight loss is your goal, you’re going to do slightly better with (Liraglutide) too.”
“GLP-1 Agonist Wins 1st Incretin Showdown” http://www.medpagetoday.com/Endocrinology/Diabetes/19706
Lisa Neff and Robert M Kushner, Division of Endocrinology, Metabolism, and Molecular Medicine, Division of General Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
GLP-1 receptor agonists have proven to be a very useful option in the treatment of type 2 diabetes, particularly in overweight and obese patients. Treatment-associated weight loss can be significant, which sets this class of medications apart from most other antidiabetic agents. In the future, GLP-1 receptor agonists may also play a role in the management of nondiabetic patients with obesity.
Dr. Alejandro said researchers are exploring another potential use for GLP-1 agonists: preserving or even increasing the number of insulin-producing islet cells in the pancreas. In animal studies, exenatide caused an increase of insulin-producing cells, he said, so it’s possible the drug could be helpful in patients who undergo islet transplantation. For many of these patients who gain insulin independence post-transplant, the effect diminishes over time.
“With exenatide,” he said, “maybe we can deal with chronic impairment of islet function.” He said that question and others will be investigated in future studies.
“Future of GLP-1 Agonists” http://americandiabetesnow.typepad.com/american_diabetes_associa/page/2/
Compiled by Farhan Guard and Eric Nielsen, Ambulatory Care Pharmacy rotation students