News Release

PRESERVE-ß 2-year study of initial combo therapy with nateglinide or glyburide + metformin

First-of-its-kind two-year study concludes combination treatment with Starlix® and metformin results in a lower incidence of hypoglycemia with equally effective glycemic control compared to combination therapy with glyburide and metformin

Peer-Reviewed Publication

Novartis Pharmaceuticals

East Hanover, June 13, 2005 – Researchers reported yesterday that in a two-year, controlled study people with type 2 diabetes receiving Starlix® (nateglinide) in combination with metformin experienced equivalent levels of overall blood glucose control and a lower incidence and severity of hypoglycemia compared to the those taking the commonly used sulfonylurea agent, glyburide, in combination with metformin. This trial is the first to prospectively evaluate the long-term safety and efficacy of the Starlix/metformin combination for two years. Researchers also observed that treatment with Starlix plus metformin was weight neutral, while participants in the glyburide/metformin arm of the trial gained about 1 kg over the two-year study period. These data were presented yesterday at the Annual Scientific Sessions of the American Diabetes Association.

"Physicians and patients are always looking for improved treatment strategies and combinations to help them achieve their target blood glucose goals," said John Gerich, M.D., University of Rochester. "Results from this trial have important clinical implications: In the past, the risk of hypoglycemia, or very low blood sugar, has been a limiting factor for early and aggressive therapy. Hypoglycemia can be life threatening for people with diabetes. There were 50 percent fewer cases of hypoglycemia with the Starlix/metformin combination."

Consistent with the mechanism of action of Starlix, which mimics the body's natural response to meals, the Starlix plus metformin group had greater reductions in post-meal glucose levels (post prandial glucose or PPG) than the glyburide and metformin group.

"Starlix's ability to lower overall blood glucose (or HbA1c) by controlling PPG is complementary to metformin's action, which lowers fasting plasma glucose levels (FPG)," continued Dr. Gerich. "A drug combination that reduces HbA1c by lowering both PPG and FPG offers doctors and patients an effective way to reach and maintain target blood glucose goals. For many patients, Starlix is an ideal first choice combination with metformin since it effectively manages mealtime glucose."

The two-year, multicenter, randomized, double-blind trial evaluated 428 drug-naïve patients with type 2 diabetes, who had inadequate glycemic control using diet and exercise alone. Patients had an HbA1c measurement between 7 percent and 11 percent. After a four-week maintenance period, when patients in both arms of the study took the lowest dose of their study medication, patients were aggressively titrated to reach a FPG goal. They were maintained on that dose for the remaining 88-week monitoring period during which safety and efficacy were evaluated.

Patients in the glyburide combination arm of the study were twice as likely to have experienced hypoglycemia (17.7% vs. 8.2%). Severe grade 2 hypoglycemia was experienced by two glyburide plus metformin treated patients. Additionally, more Starlix-treated patients completed the two-year study (64.4%) compared to glyburide plus metformin patients (58.4%). Patients receiving Starlix plus metformin treatment did not experience weight gain, while study participants receiving glyburide/metformin gained about 1 kg.

Highly significant reductions from a mean HbA1c baseline of 8.35 were observed in both treatment groups, and these reductions were sustained over the two years of the study. Patients in both groups achieved a mean HbA1c at the end of the study below the American Diabetes Association recommended target of 7% (6.9 % and 6.8% for Starlix and glyburide respectively). These reductions were sustained for the full two years of the study. There was no statistically or clinically significant difference between treatment groups in the reduction of HbA1c levels.

Starlix plus metformin therapy also had a statistically significant effect on post-meal glucose levels (PPG) compared to the glyburide and metformin group. This positive effect on PPG levels is a result of Starlix's ability to stimulate rapid, glucose-dependent insulin secretion that mimics the body's natural response to meals.

"As a company dedicated to improving the lives of people with diabetes, Novartis is actively working to deliver new and better treatment options," said Michelle Baron, M.D., Senior Medical Director. "The data presented today suggest that early combination treatment with Starlix helps patients maintain long term glucose control with significantly less hypoglycemia than combination treatment with glyburide, the must commonly prescribed sulfonylurea for type 2 diabetes."

Diabetes affects about 170 million people worldwide and, according to the World Health Organization, that number will double to 366 million by 2030. The U.S. Centers for Disease Control estimates that 18 million Americans have diabetes, making it the sixth leading cause of death in the United States and a major contributor to heart disease, stroke, blindness, kidney disease and non-traumatic leg and foot amputations.

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About Starlix
Starlix works by stimulating pancreas to release insulin, a hormone that controls the amount of glucose in the blood. Starlix is indicated as monotherapy in patients with type 2 diabetes whose hyperglycemia cannot be adequately controlled with diet and exercise and who have not been chronically treated with other oral antidiabetic agents. In patients whose hyperglycemia is inadequately controlled with metformin, or after a therapeutic response to a thiazolidinedione, Starlix may be added to, but not substituted for, these drugs. Patients who have been chronically treated with a sulfonylurea should not add or be switched to Starlix. The most common adverse events associated with Starlix vs. placebo are upper respiratory infection, back pain, flu symptoms, dizziness, and arthropathy. Starlix is also approved in many countries around the world for the treatment of type 2 diabetes. Nateglinide is licensed from Ajinomoto Co., Inc.

This press release contains certain "forward-looking Statements", relating to the Company's business, which can be identified by the use of forward-looking terminology, such as "suggest", "can become" and "potentially" or similar expressions or by discussions of strategy, plans, intentions or potential outcomes. Such statements include descriptions of the Company's development programs and descriptions of new indications expected to be approved by the regulatory authorities and introduced by the Company and anticipated customer demand for such products as well as products in the Company's existing portfolio. Such statements reflect the current views of the Company with respect to future events and are subject to certain risks, uncertainties and assumptions. There can be no guarantee that any product or potential new indications for existing products will be commercialized in any market. Many factors could cause the actual results, performance or achievements of the Company to be materially different from any future results, performances or achievements that may be expressed or implied by such forward-looking statements. These factors include, among other things, unexpected regulatory delays, uncertainties relating to clinical trials and product development, the introduction of competing products, increased government pricing pressures, and the Company's ability to obtain or maintain patent and other proprietary intellectual property protection as well as other factors discussed in the Company's Form 20-F filed with the Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as anticipated, believed, estimated or expected.

About Novartis
Novartis Pharmaceuticals Corporation researches, develops, manufacturers and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG (NYSE: NVS) – a world leader in pharmaceuticals and consumer health. In 2004, the Novartis Group's businesses achieved sales of USD 28.2 billion and pro forma net income of USD 5.6 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 81,400 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.

Please note: The study highlighted in the press release above appears in the September 2005 issue of Diabetes Care, vol. 28, no. 9, pp. 2093-2099, http://care.diabetesjournals.org/cgi/content/abstract/28/9/2093

The study was also part of the 2005 American Diabetes Association (ADA) Annual Scientific Sessions. For more information, please contact Alison Poole, for Novartis Pharmaceuticals, at 212.453.2356.

Contacts

Karen Sutherland
Novartis Pharmaceuticals Corporation
Tel: 862.778.0323
karen.sutherland@novartis.com

Alison Poole
Fleishman-Hillard
Tel: 212.453.2356
poolea@fleishman.com


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