by Ed Bryant
For decades, diabetes researchers thought type 1 diabetes was simply about lack of insulin. Their model of euglycemia, normal blood glucose, was a balancing act between two hormones, insulin and glucagon. All diabetes medication either stimulated, replaced, or augmented the action of one of these two, and that there might be another hormone at work, a third piece of the puzzle, was not considered.
We have another missing piece, now. Amylin Pharmaceuticals, Inc., a San Diego, California based company, has been researching the human hormone amylin, and their findings are fascinating. Their product, pramlintide (trade name Simlyn), was approved by the FDA on March 16, 2005.
Amyloid, the parent compound, was first noted about a century ago, by pathologists performing autopsies; it occurred in the pancreas. In the 1980s, the chemical was analyzed, and the peptide amylin sequenced from it. Because naturally-occurring human amylin is too thick and viscous to inject, Amylin Pharmaceuticals developed its injectable analog, pramlintide (Simlyn).
These two hormones are both produced in the Beta cells of the human pancreas. A type 1 diabetic, deficient in insulin, is equally deficient in amylin. A type 2 diabetic may exhibit a lesser amylin deficit. But what does amylin do?
Amylin appears to have a moderating effect on blood glucose absorption, from the gut into the blood. It acts as a set of brakes, slowing and managing meal-derived glucose inflow, controlling pancreatic glucagon secretion, and thus regulating hepatic (liver) glucose production. It smooths the "peaks and valleys" of blood sugar fluctuation, improving overall glycemic control.
In studies where Hemoglobin A1c test results were compared between those who used both insulin and Simlyn, and those who used only insulin, the A1c test results of those who used the injectable amylin analog were significantly lower than those who did not.
Clinical trials also revealed that most overweight diabetics who received Simlyn lost weight, while most lean diabetics, given the same medications, did not lose weight. Although the mechanism that produced these pleasant, unexpected findings is not yet clear, I find it exciting, as achieving and maintaining ideal weight contributes to good health, a sense of well-being, and for some, a reduction in the amount of insulin needed to maintain good control.
At this time, Simlyn use is by injection, and the medication is not drawn up with insulin. Simlyn users take an extra injection. This requires motivation.
Many diabetics have experienced episodes of severe hypoglycemia, dangerously low blood sugars. "Tight control," multiple-test, multiple-injection therapy to keep the blood sugars as close to a non-diabetic "normal" as possible, cuts risk of diabetes complications, but increases the risk of "hypos" -- and by extension, medications that improve tight control (like Simlyn) can increase the risk of running too low. The FDA approved Simlyn for all insulin-using diabetics (type 1 or insulin-using type 2) who cannot achieve consistent euglycemia with insulin alone. People whose diabetes is "brittle" in spite of their best efforts should ask their doctors to consider Simlyn. As with many medications, I expect the prescribing instructions to be widened somewhat, as doctors learn more about the medication. Right now, what matters is that insulin users have a new tool to help them control their blood sugars.
Lightning rarely strikes twice in the same place -- but it just did. Almost bled white in the long wait for FDA approval of Simlyn, Amylin has just had its second breakthrough FDA approval, April 29, 2005, just weeks after the first.
For several years, Amylin researchers, in partnership with Eli Lilly and Company, have been studying Extendin-4, a manufactured analog of the human hormone glucagon-like-peptide (GLP-1). In these "AMIGO" studies (Access diabetes Management for Improving Glucose Outcomes), reviewed in the journal Diabetes Care, the drug showed promise. Now it is here, and will be sold under the trade name Byetta.
Intended for type 2 diabetics who are using a sulfonylurea, metformin, or both, and who are not achieving adequate glucose control, Byetta is administered by injection. The drug is described as "adjunctive therapy" (i.e. It supplements, it does not replace, your established sulfonylurea and/or metformin therapy). Byetta is not a substitute for insulin in insulin-requiring patients ("maxed-out" type 2s) and should not be used for treatment of type 1 diabetes. Other cautions include a warning not to use where end stage renal disease or severe renal impairment are present.
Outside the USA, Lilly will handle distribution. Within the United States, the companies will co-promote the product. Lilly is expected to file shortly for regulatory approval to market Byetta in Brazil and Mexico, and to file for European regulatory approval in 2006.
Stay tuned, and talk to your doctor about these new medications.
Amylin Pharmaceuticals' website: www.amylin.com