nateglinide

• Brand name in US: Starlix
• Class: meglitinides (nonsulfonylurea oral hypoglycemic agents).
• For: Monotherapy for type 2 diabetes, or combination therapy when administered with metformin.
• Route of Administration: oral. Available in 60 and 120 mg doses; one dose is taken with each meal, three times daily.
• Action: enhances insulin secretion; works differently than sulfonylurea; fast-acting, and short duration of action concentrates its effect around meal time.
• manufacturer: Novartis AG licenses Starlix from Ajinomoto Co. of Japan and has a co-marketing agreement with Merck KgaA (not affiliated with Merck & Co.) within Europe and certain other countries outside the U.S.
• Status: New Drug Application filed with FDA on December 21, 1999; approved December, 2000; available soon in the USA. Already approved in Japan, Switzerland and several other countries.
• Similar drugs: repaglinide (Prandin).
• Sources of Information: DRUG Infoline, February, 2000; press release from Novartis, 2 September 1999.

Novartis Drug Alters Picture for Diabetes

By Ron Winslow, Staff Reporter, The Wall Street Journal, 12/27/00

A new drug developed by Novartis AG for patients with type 2 diabetes helps control mealtime blood-glucose levels and could help lead to a shift in strategies for treating the disease.

The drug, called Starlix, works by leveling off spikes in blood-sugar levels that typically occur during and immediately after meals. Researchers say these so-called postprandial increases are an often-overlooked problem for diabetics that if left unchecked may cause serious long-term damage to the heart and other organs. The drug was approved by the Food and Drug Administration late on Friday.

An estimated 16 million Americans suffer from diabetes, about 95% of them from the type 2 form of the disease in which the body fails to produce enough insulin to control blood-glucose levels or fails to efficiently use the insulin that is produced. (In type 1 diabetes, also known as juvenile diabetes, the body's insulin-producing beta cells are destroyed and thus don't make any insulin.)

The standard way for doctors to diagnose diabetes and for patients to track their disease is by measuring fasting blood-sugar levels and through a test known as hemoglobin A1C. Most oral medicines used to treat diabetes aim to help the body better use what insulin the beta cells produce. For years, doctors have largely ignored the mealtime blood-sugar levels, or assumed that well-controlled fasting levels, such as those registered in the morning before eating, were adequate to fend off or delay progression of the disease.

"We didn't know that postprandial glucose was of any particular biological importance," said Lawrence S. Phillips, a diabetes expert at Emory University School of Medicine in Atlanta. "Now, there is increasing epidemiological evidence that postprandial glucose is very important, not only as part of the pattern of diabetes, but in increasing risk" of cardiovascular disease.

Starlix, the first [sic] of a new class of agents, quickly stimulates beta cells in the pancreas to secrete insulin, but because it is short acting, quickly stops acting on those cells, qualities that Dr. Phillips said make it particularly well-suited to treat mealtime blood-sugar levels. The pill can be taken just a minute or so before each meal, making it convenient for patients. Because of its short action, he added, it doesn't linger in the body where it might cause overproduction of insulin and lead to dangerously low blood-sugar levels.

"Other drugs bind to the same receptor, but none have the same time course of action," said Dr. Phillips. He said the new drug could lead doctors and patients to devise treatment strategies focused on both traditional blood-sugar levels, as well as those that fluctuate with meals. He was an investigator on the major Novartis-sponsored trial that led to approval by the FDA.

In that trial, involving 701 patients, Starlix, also called nateglinide, proved effective in both blunting blood-sugar spikes associated with meals and in lowering overall blood sugar as measured by the hemoglobin A1C test. The agency approved the drug both as a stand-alone therapy and for use in combination with metformin, another diabetes pill marketed as Glucophage by Bristol-Myers Squibb Co. The combination treatment led to greater reductions in hemoglobin A1C than either Starlix or metformin alone.

Dr. Phillips said initial studies have also shown Starlix to be effective when used in combination with another new class of diabetes pills known as the glitzones, which work by improving the body's use of the insulin that it already produces. But those data weren't part of Novartis's application for approval to the FDA.

Novartis said side effects associated with Starlix were minimal, with low blood sugar being reported by 2.4% of patients who took the medicine in several studies undertaken to show its effectiveness.

Starlix, already approved in Japan, Switzerland and several other countries, is one of several potential big-selling drugs that Novartis expects to launch within the next year in the U.S. The company has indicated it intends to invest heavily in marketing the drug.

Dr. Phillips suggested that the drug's success will depend on the willingness of patients to take pills three times a day, instead of the once- or twice-daily regimen typical of other pills. And it will likely require more intensive measuring of blood-sugar levels, not only in the morning before meals, but after meals as well, something "we're not used to," he said.

At the same time, the potential market is enormous and growing. Public-health officials in the U.S. view diabetes as a public-health crisis, because its prevalence has soared during the past decade -- a reflection of a similarly sharp rise in obesity and overweight people, owing in part to unhealthy diets and a more sedentary lifestyle.

Novartis licenses Starlix from Ajinomoto Co. of Japan and has a co-marketing agreement with Merck KgaA (not affiliated with Merck & Co.) within Europe and certain other countries outside the U.S.

Also see

http://www.starlix.com by the manufacturer, Novartis AG.