Issue 97 Item 3 Item #3 Revisited from July 17, 2001, Issue 61. See current upda

David D'Alessio, M.D., from the University of Cincinnati Medical Center, has been studying the hormone GLP-1 to bring down the glucose levels in type 2 diabetics. The hormone is made in the intestine and secretes insulin, while also stimulating insulin production. GLP-1 seems to stimulate the development of new islets and islet growth." Islet cells are a group of cells found within the islets of Langerhans in the pancreas. Islet cells, known as beta cells, are responsible for making and secreting insulin, the hormone that controls the level of sugar in the blood. In type 2 diabetics, these cells either don't produce enough insulin and/or their body is resistant to the insulin they do produce. GLP-1 could help change that.

Dr. D'Alessio says there are a number of ongoing human clinical trials with GLP-1 and the results are likely to be released by next year. He says among the many benefits of GLP-1 are:

· They stimulate insulin production and secretion

· They block the effects of glucagon

· They may slow the entrance of glucose into cells after a meal

He says all of these factors tend to lower blood glucose.

The major problem with GLP-1 right now is that it's short-acting. It's also administered by injection. Dr. D'Alessio hopes to see the development of a long-acting form of the hormone (which could be infused throughout the day) or an oral form of the hormone. He says studies have been started in both of these areas. He says they may study the hormone in a small group of patients but he has no large studies in the works at the University of Cincinnati. He says, "We lay the groundwork for people to do human studies at larger or multi-center institutions."

UPDATE on GLP-1, March 24, 2002,

Last week Lancet published the effect of 6-week course of glucagon-like peptide 1 (GLP-1) on glycemic control, insulin sensitivity and B-cell function in type 2 diabetes. Lancet 359, 9Mar2002, 824-830.

GLP-1 could be a major breakthrough for Type 2 diabetes. This has the potential of ending diabetes 2 as we know it today. Results of the study:
· fasting glucose was better controlled
· HbA1c decreased by 1.3% (in 6 weeks!)
· fructosamine fell to normal (in 6 weeks!)
· fasting free fatty acids dropped 30%
· 8 hour free fatty acids dropped 23% (who needs fasting!)
· gastric emptying decreased
· weight dropped 4.2 lbs (in 6 weeks!)
· appetite was reduced
· insulin sensitivity improved
· Beta cell function improved
· No important side effects were seen!

Insulin resistance and Beta cell dysfunction characterize diabetes 2. Glucose control deteriorates with time, primarily through progressive Beta cell dysfunction. Although good control can diminish complications, the deterioration of the Beta cell function may be inevitable. (UKPDS 33) Lancet 1998 352:837-53

Glucagon-like Peptide-1 (GLP-1) is produced in the intestine. It responds to food and is important in regulating after meal glucose. When you have diabetes, GLP-1 is reduced. In the short term, when you give GLP-1 to a person, all the features of diabetes disappear. Diabetalogica 1993 36; 741-44

In rats, GLP-1 reverses age dependent decline in Beta cells, and stimulates new growth of numbers of Beta cells - new Beta cells are born. Diabetes 1999; 48: 2270-76
New Pharmaceuticals in the Pipeline
There are four companies that are racing to get GLP-1 out on the market. The first may be out within 6 months.

1. AC-2993, also known as synthetic exendin-4 from Amylin, completing Phase III trials

2. Insulinotropin from Scios, Novo Nordisk

3. Betatropin, an investigational compound developed by Restoragen Inc

4. ZP10, Zealand Pharmaceuticals a joint venture with Elan Corp