PRESERVE-▀ 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

East Hanover, June 13, 2005 ľ 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-na´ve 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.

Source: Eurekalert & others

Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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