Various drugs are currently used for the treatment of diabetes. Several reports on overdose of these drugs, especially on sulfonylurea and metformin, have been published (1,2); however, few such publications are available on nateglinide, a rapid insulin secreatagogue. We report the first case of attempted suicide by nateglinide overdose. A 30-year-old Japanese nondiabetic woman was transferred to the emergency department of our hospital 1 h after (6:30 a.m.) ingesting 3,420 mg (38 tablets, 90 mg each) of nateglinide, which was prescribed to her diabetic partner. She had a mild psychiatric history and used minor tranquilizers occasionally. Upon arrival to the hospital, she was able to walk unaided though she seemed drowsy. Blood pressure was 120/80 mmHg, pulse rate was 78 beats/min, and peripheral oxygen saturation was 96% on room air breathing. Blood glucose concentration measured at arrival (1 h after ingesting nateglinide: 7:30 a.m.) was 2.0 mmol/l. A bolus dose of 40 ml of 50% glucose was injected intravenously (iv). At 8:30 a.m., blood glucose was increased to 3.1 mmol/l. Another 40 ml of 50% glucose was iv injected again, which resulted in normalization of blood glucose concentration. However, at 10:30 a.m., blood glucose was 1.2 mmol/l. Another 40 ml of 50% glucose was iv injected, and blood glucose concentration returned to 4.2 mmol/l and immunoreactive insulin was 11 μU/ml. At 11:30 a.m., blood glucose concentration was 2.2 mmol/l. At that stage, a bolus of 20 ml of 50% glucose was iv injected, and a 10% glucose drip infusion was started (40 ml/h). At 12:30 p.m., the blood glucose concentration was 3.0 mmol/l, and at 1:30 p.m., the blood glucose returned to normal range under 10% glucose infusion (40 ml/h), and no more hypoglycemic episodes were observed. The next day, the blood glucose was 5.5 mmol/l and immunoreactive insulin was 5.0 μU/ml without glucose infusion, and she was discharged without complications. Thus, the prolonged hypoglycemic effect of nateglinide continued for 6 h, and intravenous glucose supplementation (totally 100 g) was sufficient to maintain euglycemia.

Nateglinide is a novel, highly physiologic mealtime glucose regulator recently approved for the treatment of type 2 diabetes. Compared with sulfonylurea, nateglinide causes rapid but short stimulation of insulin secretion. Factitious sulfonylurea overdosages usually result in prolonged hypoglycemia (usually >48 h in a case report [3]), and intravenous glucose supplementation or octreotide injection is necessary to maintain euglycemia. To our knowledge, overdosage of nateglinide has not been previously reported. Repaglinide-induced factitious hypoglycemia has been reported, but the dose taken was equivalent to that used clinically (4). In normal rats fasted for 17 h, oral administration of nateglinide produced a prompt (within 1 h) and dose-dependent reduction in blood glucose, but significant reduction was no longer noticeable after 3 h, even at the dose of 100 mg/kg (5). In comparison, glibenclamide showed a slower onset of its hypoglycemic action and caused a sustained decrease in blood glucose levels for at least 6 h at a dose of 1 mg/kg (5).

In conclusion, an overdose of oral nateglinide elicited prompt but mild, relatively short lived, and reversible hypo-glycemia. These features of hypoglycemia resembled the hypoglycemic effects of nateglinide in regular therapeutic dosages.

Klonoff DC, Barrett BJ, Nolte MS, Cohen RM, Wyderski R: Hypoglycemia following inadvertent and factitious sulfonylurea overdosages.
Diabetes Care
Teale KFH, Devine A, Stewart H, Harper JH: The management of metformin overdose.
Klonoff DC: Association of hyperinsulinemia with chlorpropamide toxicity.
Am J Med
Hirshberg B, Skarulis MC, Pucino F, Csako G, Brennan R, Gorden P: Repaglinide-induced factitious hypoglycemia.
J Clin Endocrinol Metab
Ikenoue T, Okazaki K, Fujitani S, Tsuchiya Y, Akiyoshi M, Maki T, Kondo N: Effect of a new hypoglycemic agent, A-4166 [(-)-N-(trans-4-isopropyl-cyclohexanecarbonyl)-D phenylalanine], on postprandial blood glucose excursion: comparison with voglibose and glibenclamide.
Biol Pharm Bull