Novartis has filed a supplemental new drug application (sNDA) for Starlix (nateglinide) for use in combination with a thiazolidinedione (TZD), a commonly used class of oral antidiabetic agents. The FDA submission is based on the findings of a 24-week study involving 402 patients with type 2 diabetes. Starlix is already indicated in combination with metformin for treatment of type 2 diabetes.

Starlix works by stimulating rapid, short-acting insulin secretion that reduces the mealtime increase in blood glucose levels and effectively lowers overall blood glucose levels. Thiazolidinediones (TZDs) improve insulin sensitivity and help control blood sugar by reducing fasting plasma glucose levels. By using Starlix in combination with a TZD, both the mealtime and fasting glucose levels will be managed, and could potentially lead to substantial reductions in HbA1c.

The FDA submission is based on the positive findings of a 24-week multicentre double-blind randomized study which compared the efficacy of Starlix (120 mg, taken before a meal) and placebo added to ongoing open label rosiglitazone (Avandia 8 mg, q.d.) in 402 patients with type 2 diabetes who had not reached target HbA1c levels on rosiglitazone alone (HbA1c 7 per cent - 11 per cent).

The study found that in patients randomized to the Starlix / rosiglitazone combination, HbA1c decreased from 8.3 per cent to 7.5 per cent, but in the placebo-treated patients, HbA1c did not change. Target HbA1c (less than 7 per cent) was achieved by 38 per cent of patients treated with the combination therapy and by 9 per cent of patients remaining on rosiglitazone monotherapy.

The study also found that in the Starlix / rosiglitazone combination patients, fasting plasma glucose decreased by 0.7 mmol/L, 2-hr post prandial glucose decreased by 2.7 mmol/L and 30-minute insulin levels increased by 165 pmol/L compared to no changes from baseline of these parameters with placebo added to rosiglitazone (p0.001).

In this study, the overall safety, tolerability and effects on lipid parameters were similar in the two treatment groups. However, the incidence of confirmed hypoglycemia in the group treated with combination therapy (PG2.8 mmol/L) was 4.5 percent (versus 0% hypoglycemia in the control group).

Starlix was approved in the United States in 2001 as monotherapy for newly diagnosed or drug-naïve patients with type 2 diabetes and as an add-on therapy for people with type 2 diabetes who are being treated with metformin, a leading oral antidiabetic agent. 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.