Recently, in a major advance, seven consecutive type 1 diabetics attained insulin independence following a procedure in which pancreatic islet cells were injected percutaneously via a catheter into the portal vein. Such a cell transplant technique is significant because it could lead to the elimination of insulin injections in the treatment of diabetes mellitus. The New England Journal of Medicine considered the findings striking enough for early release, and if these results are confirmed with other studies, it could mean the conquest of insulin-dependent diabetes. Though the patients would need to take immunosuppressant drugs, the findings nevertheless represent a breakthrough in the treatment of a disease that has had many generations of sufferers.
In fact, diabetics have had much to rejoice about in the last few years. There have been several new developments in the treatment of this disease, including new drugs and delivery systems. For example, the insulin pen is a handy device for administration of premixed insulin to insulin-dependent diabetics. Insulin pens offer greater convenience and flexibility for insulin-dependent diabetes and could be a major asset for improving compliance. The pen offers more accurate dosing, which in turn leads to a better long term outcome. Of course, in the future, pancreatic cell transplants could eliminate the need for insulin injections, but till then, the insulin pen would offer a better way to administer insulin.
Clinical trials have also shown success with inhaled insulin, with insulin administered by inhalation reducing blood glucose faster than traditional injections. An inhaled form of insulin, which has blockbuster potential, could be introduced in the market by the next year. In the future, we could also see the use of surgically implanted insulin pumps with automatic glucose monitors designed to monitor blood sugar levels and automatically deliver the correct amount of insulin, facilitating accurate blood sugar control. New types of synthetic insulin are also in the making. The short-acting insulin lispro acts in about 5 minutes, rather than 20-30 minutes with traditional insulin. Other new methods of tackling diabetes mellitus can also come from gene therapy, now under investigation.
Relatively new drug categories for type 2 diabetes are the thiazolidinediones, which enhance insulin action, and the meglitinides, which enhance insulin supply. The thiazolidinediones (commonly known as glitazones) are oral antidiabetic agents that enhance insulin sensitivity in peripheral tissues. The first agent to be introduced was troglitazone, which was associated with hepatocellular injury and death due to liver failure, and was later withdrawn in the U.S. Rosiglitazone is a new and more potent member of this class, whereas pioglitazone has intermediate potency. Rosiglitazone and pioglitazone have a better safety profile than troglitazone.
The meglitinides are another class of oral antidiabetic agents. Among these, repaglinide was the first drug to be introduced, and it acts by stimulating insulin secretion in a glucose-dependent manner. Repaglinide has a rapid onset of action and short half-life, making it suited for regulation of glucose related to meal intake. Nateglinide is another drug in this class with a more rapid onset and shorter duration of action than repaglinide.
The alpha glucosidase inhibitors, including acarbose and miglitol, delay carbohydrate absorption. They inhibit the intestinal enzymes that hydrolyze oligosaccharides and disaccharides to glucose and other monosaccharides, thus delaying glucose absorption and reducing postprandial hyperglycemia. Of course, type 2 diabetics can also draw on the proven efficacy of established agents such as the sulphonylureas (chlorpropamide, tolbutamide, glipizide, glimepiride, glyburide and others) and the biguanides (e.g., metformin).
Undoubtedly, 135 million diabetics worldwide, including 25 million in India, now have a choice of treatments that has never been wider. And with many interesting new developments on the way, the 2.8 million deaths that occur every year due to diabetes could soon be a thing of the past.
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This article was published in Pharma Business 7th July 2000.
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