In a general practice observation study 11,476 patients with type 2 diabetes pretreated with oral antidiabetic drugs, mainly metformin, received an oral combination therapy of nateglinide with metformin. Mean age+/-SD of the participants was 61+/-10.3 years, range 19 to 97 years, the body mass index (mean+/-SD) was 29.4+/-4.5 kg/m2, range 14.9 to 68.7 kg/m2. The observation period lasted 3 to 4 months (mean 96 days). During this period the mean HbA1c decreased from 8.4 % to 7.2%, displaying a positive relation between initial value and degree of reduction. Postprandial glucose levels dropped from a mean of 210 to 152 mg/dl. At the beginning of the study the combination of the two target values for glucose control, HbAc <7% and postprandial glucose <180 mg/dl, was reached in only 5.8% of the participants, at the end in 44.9%. During the therapy, weight and blood pressure dropped slightly. Adverse events were reported in only 2.9% of the patients and involved a broad range of symptoms with mild gastrointestinal complaints being predominant (1.3%). This study demonstrated that the combination of nateglinide with metformin can be considered as an effective and safe option for treatment of patients with type 2 diabetes, with additional beneficial effects on body weight and blood pressure.