Researchers reported 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 Nateglinide/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 at the Annual Scientific Sessions of the American Diabetes Association ( ADA ).
" Physicians and patients are always looking for improved treatment strategies and combinations to help them achieve their target blood glucose goals," said John Gerich, 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 Nateglinide/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 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.
Starlix works by stimulating pancreas to release insulin.
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.
Source: Novartis, 2005