• J-M González-Clemente and Spanish Nateglinide Study Group.
• Department of Diabetes, Endocrinology and Nutrition, Hospital de Sabadell, Sabadell, Spain. gonclem@yahoo.es
• Eur. J. Clin. Invest. 2008 Mar 1; 38 (3): 174179174-9.

BackgroundIt has been speculated that oral hypoglycaemic agents that block K-ATP channels could potentially increase blood pressure by blocking such channels in vascular myocytes. No information about this issue exists regarding nateglinide.DesignA multicentre, double-blind, placebo-controlled, randomized trial was conducted in 109 drug-naive 30- to 75-year-old patients with type 2 diabetes and < 5 years of diabetes diagnosis, who are not taking antihypertensive drugs. These patients were assigned to receive placebo or fixed doses of nateglinide (120 mg before each main meal: breakfast, lunch and dinner) and evaluated at weeks 0 and 12 for (i) body mass index and blood pressure; (ii) standard laboratory tests, including haemoglobin A1c (HbA1c) and fasting plasma glucose; and (iii) incremental area under the curve for glucose and C-peptide after a standardized liquid breakfast challenge, homeostasis model assessment (HOMA)-B% (as surrogate of beta-cell activity) and HOMA-S% (as surrogate of insulin sensitivity).ResultsAt the end of the follow-up period, patients in the nateglinide group (n = 55), compared to patients in the placebo group (n = 54), showed lower values of HbA1c (6.7 +/- 0.6 vs. 7.2 +/- 0.7%, respectively; P < 0.001), fasting plasma glucose (7.9 +/- 2.1 vs. 8.5 +/- 2.0 mmol L(-1); P = 0.023) and systolic blood pressure (125.3 +/- 15.4 vs. 129.3 +/- 18.7 mmHg; P = 0.015), and higher values of HOMA-B%[75.7 (51.8-99.4) vs. 57.7 (42.2-83.4); P = 0.033]. A positive correlation was found between changes in HbA1c and systolic blood pressure in the nateglinide group (r = 0.355, P = 0.011).ConclusionsIn drug-naive patients with type 2 diabetes, the improvement in glycaemic control with nateglinide is associated with a decrease in systolic blood pressure.

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