Postmarketing surveillance study of nateglinide in Japan

Abstract

Nateglinide is an oral antidiabetic medication that acts through rapid, short-term stimulation of insulin production. This study was undertaken to identify the incidence and nature of adverse effects of nateglinide and to assess its efficacy in clinical practice. Patients (n = 3254) were recruited from 606 centers in Japan with a 12-week observation period. Pretreatment and posttreatment values were obtained for fasting blood glucose, postprandial blood glucose, hemoglobin A1c (HbA1c), triglycerides, cholesterol, and body mass index. All adverse events were reported, along with standard laboratory blood variables. The incidence of adverse events was 7.40%; hypoglycemia, including hypoglycemic symptoms, was reported as the most prevalent (1.62%). Adverse events were observed more frequently in patients with hepatic or renal dysfunction; no significant findings were noted in the remaining patient population. The efficacy rating determined by the treating physicians was 76.40%. HbA1c decreased by 0.81% from 7.70+/-1.53% to 6.89+/-1.22%, postprandial glucose decreased by 54.05 mg/dL from 228.91+/-73.69 mg/dL to 174.86+/-62.86 mg/dL, and fasting glucose decreased by 23.73 mg/dL from 164.15+/-51.42 mg/dL to 140.43+/-42.63 mg/dL. These effects were most marked in patients who were previously medication naïve or who had been diagnosed with diabetes for a short period. Mean body mass index decreased, and nateglinide was equally effective in obese patients. Nateglinide showed good therapeutic effect when used as the first choice in patients with a short duration of diabetes, and in those with no history of previous treatment. Moreover, nateglinide seemed to be useful for the treatment of elderly patients and obese patients.

Nateglinide and glibenclamide metabolic effects in naïve type 2 diabetic patients treated with metformin

“…Other authors have compared the hypoglycemic potential of nateglinide and glibenclamide, concluding that nateglinide has a lower hypoglycemic potential, because of its better insulinotropic effect (39). Its safety has also recently been confirmed by post‐marketing surveys (40).…”

A review of methods used in assessing non-serious adverse drug events in observational studies among type 2 diabetes mellitus patients

“…Administrative databases were mainly used for cardiac ADEs, and laboratory/clinical values often included hepatic or metabolic problems or weight increase (Table 2). Four studies identified the same ADE, either hypoglycaemia or hepatic dysfunction, using more than one method, in particular a combination of laboratory values and other methods [25-28]. …”

Nateglinide - current and future role in the treatment of patients with type 2 diabetes mellitus

“…Generally, this analysis suggested that the incidence of adverse events in elderly patients was similar to that in the overall patient population (69). In Japanese post‐marketing surveillance, the incidence of adverse events in patients aged >65 years was also similar to that in patients aged <65 years (59).…”

“…However, nateglinide at 120 mg may further decrease fasting blood glucose and HbA 1c levels compared with nateglinide at 60 mg (53). Suitable patients for nateglinide monotherapy include treatment‐naïve patients; patients at an early stage of diabetes, or with a short disease history; those with moderately elevated fasting plasma glucose and HbA 1c levels, including obese people; those with more severe diabetes but who still have insulin secretion ability; following treatment with insulin for reduction of glucose toxicity; and elderly patients, but switching from sulfonylureas to nateglinide is not recommended (58,59).…”

“…Analysis of over 3500 patients treated with nateglinide in Japan between 1999 and 2003 revealed that adverse effects were reported by approximately 7.5% of patients. Hypoglycaemia was rare (1.6–2.1%) and BMI showed no significant change over 15 months of treatment (59,84,85).…”