Basel, 28 May 2003 - Results of a new study to be published in the June edition of Diabetes Care find that the addition of Starlix® (nateglinide) improves glycemic control and is well-tolerated in patients whose type 2 diabetes is inadequately controlled by taking rosiglitazone alone. The double-blind study demonstrated that the addition of nateglinide to rosiglitazone (Avandia*) monotherapy significantly reduced both HbA1c and post-prandial glucose levels and also restored insulin levels, with a favorable safety and tolerability profile.
"The study showed that nateglinide produced a meaningful improvement in overall glycemic exposure in patients inadequately controlled with rosiglitazone alone, without exacerbating known side-effects of this class of medication, the thiazolidinediones," said Vivian Fonseca, M.D., Medical Director from Tulane University Medical Center New Orleans, Louisiana and the lead investigator of the study.
Previous research has shown that over time there is a progressive need for multiple therapies in order to treat type 2 diabetes and maintain a target HbA1c of less than 7.0%.1
The team of researchers from 30 centers in North America carried out the 24-week double blind randomized study to compare the efficacy of nateglinide (120mg) and placebo added to ongoing open-label rosiglitazone (8mg) in patients with type 2 diabetes, who had an HbA1c level between 7% and 11%. The 402 patients taking part in the trial had been diagnosed with type 2 diabetes at least six months previously and treated with rosiglitazone monotherapy (8 mg), diet and exercise for at least three months prior to the trial.
In patients randomized to nateglinide there was a clinically and statistically significant decrease in HbA1c from the baseline of 8.3% to 7.5% (p<0.0001). Target HbA1c (<7.0%) was achieved by 38% of patients treated with nateglinide/rosiglitazone combination therapy and by 9% of patients remaining on rosiglitazone monotherapy (p<0.001).
"The two agents work in a complementary way to address the dual defect in type 2 diabetes," explained Dr. Fonseca. "While rosiglitazone reduces insulin resistance, nateglinide stimulates insulin secretion at mealtime and targets post-prandial blood glucose."
In nateglinide-treated patients, there were clinically and statistically significant reductions in fasting plasma glucose (FPG) and 2- hour post-prandial glucose (PPG) levels. In contrast, in patients maintaining rosiglitazone monotherapy, there were no changes in either FPG or PPG.
Previous studies have shown the effects of nateglinide on meal-stimulated insulin levels are clearly apparent within 15 minutes of food consumption and such effects decrease in a glucose dependent manner as the plasma glucose level drops.2 Through this selective stimulation of early insulin release, nateglinide greatly reduces post-prandial glucose levels while minimizing the overall insulin exposure.
Research has shown that improved glycemic control, as measured by a reduction of HbA1c levels, may lead to a dramatic lowering of deaths and complications from diabetes. Even a 1% reduction in HbA1c can correlate to a 21% decrease in deaths from diabetes and a 14% decrease in heart attacks.3
About Starlix
Starlix was approved in the United States in 2001 both as a monotherapy for drug-naïve patients with type 2 diabetes and also in combination with metformin, a leading oral antidiabetic agent. In December 2002, Novartis filed a supplemental new drug application (sNDA) for Starlix for use in combination with a thiazolidinedione (TZD). Starlix has an excellent safety and tolerability profile across all clinical trials. Starlix is also approved in many countries around the world for the treatment of type 2 diabetes. Nateglinide is licensed to Novartis Pharma AG 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 "would provide" and "would be managed" 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.
Novartis AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of USD 20.9 billion and a net income of USD 4.7 billion. The Group invested approximately USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 77 200 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
References:
1. UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes. (UKPDS 33). Lancet 1998; 352:837-853
2. Horton E. et al, Nateglinide alone and in combination with metformin improves glycaemic control by reducing mealtime glucose spikes in type 2 diabetes. Diabetes Care 2000; 23:1660-1665
3. Stratton IM, Adler AI, Neil AW, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000; 321:405-412
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* Avandia is a trademark of GlaxoSmithKline
