Improvement of glycaemic control by nateglinide decreases systolic blood pressure in drug-naive patients with type 2 diabetes.
BACKGROUND
It 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.


METHODS
A 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).


RESULTS
At 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).


CONCLUSIONS
In drug-naive patients with type 2 diabetes, the improvement in glycaemic control with nateglinide is associated with a decrease in systolic blood pressure.
González-Clemente
J-M
JM
Department of Diabetes, Endocrinology and Nutrition, Hospital de Sabadell, Sabadell, Spain. gonclem@yahoo.es
D000328:Adult; D000368:Aged; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D001794:Blood Pressure / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D003510:Cyclohexanes / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077715:Nateglinide; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D002784:Cholesterol; D003510:Cyclohexanes; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D000077715:Nateglinide; D010649:Phenylalanine; D014280:Triglycerides