Differences in glucose tolerance between fixed-dose anti hypertensive drug combinations in people with metabolic syndrome

OBJECTIVE - We sought to test the hypothesis that a fixed-dose combination of trandolapril/verapamil-SR (T/V) is superior to a fixed-dose combination of losartan/hydrochlorothiazide (L/H) on glucose tolerance in hypertensive patients with impaired glucose tolerance (IGT). RESEARCH DESIGN AND METHODS - A prospective, randomized, open-label blinded-end points. design was used to assess the effects of a T/V versus L/H combination in patients with IGT and hypertension (n = 240) followed for up to 1 year. Doses were titrated to a systolic blood pressure < 130 mmHg. Primary outcome was change from baseline in a 2-h glucose on oral glucose tolerance test (OGTT) at study end (mean [+/- SD] at follow-up, 46.9 13.5 weeks). Secondary outcomes included changes in insulin sensitivity, office and 24-h ambulatory blood pressure, incidence of new-onset diabetes, lipids, and inflammatory markers. Data are expressed as means SE unless otherwise noted. RESULTS - Changes at study end were noted in 2-h OGTT glucose (T/V -0.21 +/- 0.36 vs. L/H +1.44 +/- 0.36 mmol/l; P < 0.001) and insulin level (-30.13 +/- 38.38vs. +84.86 +/- 38.33 pmol/l, respectively; P = 0.025). Worsening of insulin resistance occurred by week 12 (T/V 0.000 - 0.001 vs. L/H -0.005 +/- 0.001; P = 0.016). A higher incidence of new-onset diabetes (T/V 11.0 vs. L/H 26.6%; P = 0.002) and HbA(1c) > 7% (2.6 vs. 9.6%, respectively; P = 0.05) occurred at study end. CONCLUSIONS - In patients with IGT, normal kidney function, and hypertension, the fixed-dose combination of T/V reduces the risk of new-onset diabetes compared with an L/H-based therapy.