Insulin and Amylin: Balancing Pancreatic Hormones to Achieve Glucose Homeostasis

Corporate-sponsored Symposium
Supported by an unrestricted educational grant from Amylin Pharmaceuticals, Inc
Monday, June 13, 2005
5:30-8:00 AM

Chair
John Buse, MD, PhD

Faculty
Steven V Edelman, MD
Stephen L Aronoff, MD
Davida F Kruger, MSN, APRN, BC-ADM

Reported by Joelle Escoffery, PhD

In spite of the fact that 8 new drug classes have become available in the last decade, more than 50% of patients still are not meeting the ADA target for glycemic control. Further, current treatments have a wide range of challenges associated with them, including durability of effect, hypoglycemia, weight gain, edema, GI side effects, and a variety of contraindications. The pathophysiology of type 2 diabetes has long been thought to be comprised of 2 underlying defects: insulin resistance and impaired insulin secretion. However, another important physiological consequence of type 2 diabetes is postprandial hyperglucagonemia. Amylin, a neuroendocrine hormone that is also secreted by the pancreatic beta cells, plays an important role in suppressing postprandial hyperglucagonemia. Amylin has also been shown to regulate gastric emptying and promote satiety.

Pramlintide, a synthetic amylin analog, has been tested among insulin-requiring patients with both type 1 and type 2 diabetes. In both groups, pramlintide treatment resulted in reductions in A1C, insulin dose requirements, and weight. When the pivotal trials were conducted, patients were not instructed to lower insulin dose. Accordingly, some hypoglycemia was observed. Likewise, pramlintide dose was not slowly titrated up in the pivotal trials, resulting in elevated rates of nausea. However, subsequent research has demonstrated that when insulin dose is lowered, risk of hypoglycemia is less, and amylin itself does not appear to cause hypoglycemia. Similarly, when pramlintide is started at a low dose and titrated up, rates of nausea significantly decline.