FDA OKs Lilly-Amylin Drug for Type 2 Diabetes

Fri Apr 29, 2005 5:38 PM BST

By Toni Clarke

NEW YORK (Reuters) - U.S. regulators have approved a diabetes drug derived from lizard saliva for patients who have not responded to other treatments, the drug's developers, Eli Lilly and Co. and Amylin Pharmaceuticals Inc., said on Friday.

The U.S. Food and Drug Administration approved exenatide, an injectable drug to be sold under the brand name Byetta, as an additional therapy for patients with Type II diabetes -- the most common form -- whose blood sugars are not sufficiently controlled by two oral medications.

Analysts expect the drug could eventually generate sales of about $1 billion to $2 billion.

Shares of Amylin fell 8 percent to $16.73 in midday trade on the Nasdaq, after earlier touching a two-year low of $16.01. Analysts, however, said the news was positive for Amylin.

The companies, which had sought approval only to market Byetta only in combination with other diabetes drugs, said that the FDA also gave conditional approval for Byetta as a stand-alone treatment, subject to further clinical trials.

Jamaison Schuler, a spokesman for Eli Lilly, said the FDA's decision to conditionally approve the drug as a stand-alone treatment is "wonderful news" as the companies had not sought such approval and indicates the agency sees promise in the drug for this use.

Some analysts, as well as Lilly, said that investors may be misinterpreting the conditional approval as a negative move.

Exenatide is Amylin's second product on the commercial market. It already sells Symlin, another diabetes treatment.

Exenatide, which is a synthetic version of saliva of the Gila monster lizard that lives in the Arizona desert, is the first of a new class of drugs known as incretin mimetics. It mimics hormones, released in the human gut in response to food, that help regulate glucose levels.

Trials of 1,446 patients showed about a 1 percent reduction in blood sugar levels in patients who took Byetta along with other oral diabetes medications, including widely used metformin and a class of older drugs called sulfonylureas.

Most patients also experience weight loss. Weight gain is seen as a risk factor for diabetes.

Patients can inject Byetta as an alternative to taking insulin, which can cause hypoglycemia, or worrisome drops in blood sugar levels that can cause fainting.

Because Byetta is not closely linked with hypoglycemia Shao said patients would not have to monitor their blood glucose levels as constantly as insulin users must.

"I'll especially recommend this drug for obese diabetics who are making their best effort to control their diets but are still not losing weight," said Dr. Stuart Weiss, an assistant professor at New York University Medical School.

Shares of Lilly, which has many drugs on the market, were unchanged at $58.00 on the New York Stock Exchange.

More than 15 million people in the United States have type II diabetes. Diabetics are unable to produce enough insulin or cannot process their insulin properly, resulting in dangerously high blood-sugar levels, which can lead to heart disease, blindness and amputations if not treated.

Amylin Chief Operating Officer Daniel Bradbury said the company has not yet set a price for the drug. He said it could face future competition from Danish drug maker Novo Nordisk, which is working on a rival medicine called Liraglutide.

Novartis AG, Merck & Co. Inc. and Bristol-Myers Squibb are also testing diabetes drugs in a different class that try to prolong the gut's natural insulin secretions.

(Additional reporting by Ransdell Pierson in New York and Susan Heavey in Washington.)

© Reuters 2005. All rights reserved

Prevention of Type 2 Diabetes With Troglitazone in the Diabetes Prevention Program

Abstract and Introduction
Abstract

The Diabetes Prevention Program (DPP) was a randomized clinical trial of prevention of type 2 diabetes in high-risk people. Troglitazone, an insulin-sensitizing agent, was used initially but was discontinued during the trial. Troglitazone therapy was compared with other DPP interventions, considering both the short-term "in-trial" results and the longer-term results after troglitazone were discontinued. From 1996 to 1998, participants were randomly assigned to treatment with metformin ( n = 587), troglitazone ( n = 585), double placebo ( n = 582), or intensive lifestyle intervention (ILS) ( n = 589). Because of concern regarding its liver toxicity, the troglitazone arm was discontinued in June 1998, after which follow-up of all participants continued. During the mean 0.9 year (range 0.5-1.5 years) of troglitazone treatment, the diabetes incidence rate was 3.0 cases/100 person-years, compared with 12.0, 6.7, and 5.1 cases/100 person-years in the placebo, metformin, and ILS participants ( P < 0.001, troglitazone vs. placebo; P = 0.02, troglitazone vs. metformin; P = 0.18, troglitazone vs. ILS). This effect of troglitazone was in part due to improved insulin sensitivity with maintenance of insulin secretion. During the 3 years after troglitazone withdrawal, the diabetes incidence rate was almost identical to that of the placebo group. Troglitazone, therefore, markedly reduced the incidence of diabetes during its limited period of use, but this action did not persist. Whether other thiazolidinedione drugs used for longer periods can safely prevent diabetes remains to be determined.
Introduction

The Diabetes Prevention Program (DPP) was a randomized clinical trial of prevention of type 2 diabetes in people at high risk of diabetes.[1] Enrollment began in 1996 with randomization to four treatment groups. Three treatments were standard healthy lifestyle recommendations plus placebo, metformin, or troglitazone. The fourth treatment was intensive lifestyle (ILS), which consisted of no drugs and the same lifestyle recommendations given to the pharmacologic groups, but the lifestyle advice was given with much more behavioral support. The details of these treatments and the results of three of the interventions have been described,[1-3] and the protocol is available at http://www.bsc.gwu.edu/dpp/protocol.htmlvdoc .

In planning the DPP (from 1994 to 1996), the research group considered testing several drugs affecting insulin secretion and sensitivity. Metformin and troglitazone, two drugs of different classes with different actions, were chosen. Metformin had been used worldwide in treating type 2 diabetes for several decades but was not approved in the U.S. until 1994. Troglitazone, an insulin-sensitizing thiazolidinedione, showed promise in improving insulin sensitivity and glucose tolerance.[4] Its use was started in the DPP in 1996 as an investigational drug. It was then approved in the U.S. for diabetes treatment in 1997 but was withdrawn from the DPP in 1998 and from the U.S. market in 2000 because of liver toxicity. In this study, we report the results of troglitazone treatment both before and after its discontinuation during the DPP.
CONTINUED

Diabetic Neuropathies

Introduction

The diabetic neuropathies are heterogeneous, affecting different parts of the nervous system that present with diverse clinical manifestations. They may be focal or diffuse. Most common among the neuropathies are chronic sensorimotor distal symmetric polyneuropathy (DPN) and the autonomic neuropathies. DPN is a diagnosis of exclusion. The early recognition and appropriate management of neuropathy in the patient with diabetes is important for a number of reasons. 1 ) Nondiabetic neuropathies may be present in patients with diabetes. 2 ) A number of treatment options exist for symptomatic diabetic neuropathy. 3 ) Up to 50% of DPN may be asymptomatic, and patients are at risk of insensate injury to their feet. As >80% of amputations follow a foot ulcer or injury, early recognition of at-risk individuals, provision of education, and appropriate foot care may result in a reduced incidence of ulceration and consequently amputation. 4 ) Autonomic neuropathy may involve every system in the body. 5 ) Autonomic neuropathy causes substantial morbidity and increased mortality, particularly if cardiovascular autonomic neuropathy (CAN) is present. Treatment should be directed at underlying pathogenesis. Effective symptomatic treatments are available for the manifestations of DPN and autonomic neuropathy.

This statement is based on two recent technical reviews,[1,2] to which the reader is referred for detailed discussion and relevant references to the literature. READ NEXT ONLINE

Metformin May Cut Risk of Cancer in Diabetics

NEW YORK (Reuters Health) Apr 21 - Patients with type 2 diabetes who are prescribed metformin appear to be at lower risk of cancer than those not treated with metformin, according to a pilot observational study reported in the British Medical Journal Online First on April 21.

Lead author Dr. Josie M. M. Evans and colleagues at the University of Dundee in Scotland explain that metformin activates the enzyme AMP activated protein kinase, which in turn is regulated by the tumor suppressor LKB1. They therefore theorized that metformin use may reduce risk of cancer.

To test their hypothesis, they performed a case-control study in which a diabetes clinical information system was linked with a database of dispensed prescriptions.

Between 1993 and 2001, nearly 12,000 patients had been newly diagnosed with type 2 diabetes, including 923 who were later diagnosed with cancer. These were matched to 1846 diabetic subjects without cancer by age, year of diagnosis and gender.

During the year prior to the cancer diagnosis, 36.4% of cases and 39.7% of controls had been given a prescription for metformin (odds ratio 0.86). The odds ratio for any exposure to metformin since 1993 was 0.79.

There appeared to be a dose-response relationship between metformin and cancer, as the odds were further reduced by increasing duration of metformin treatment and total amount of metformin dispensed.

The research team is now in the planning phase of a large cohort study linked to a cancer registration database, they note.

BMJ Online First 2005.