Differences in glucose tolerance between fixed-dose antihypertensive 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).


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 +/- 38.38 vs. +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 HbA1c >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.
Bakris
George
G
Department of Preventive Medicine, Rush University Hypertension Center, Chicago, IL 60612, USA. gbakris@medicine.bsd.uchicago.edu
Molitch
Mark
M
Hewkin
Ann
A
Kipnes
Mark
M
Sarafidis
Pantelis
P
Fakouhi
Kaffa
K
Bacher
Peter
P
Sowers
James
J
D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism*; D015992:Body Mass Index; D049628:Body Size; D001835:Body Weight; D004359:Drug Therapy, Combination; D005260:Female; D018149:Glucose Intolerance / Q000150:complications*; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications*; D008875:Middle Aged; D018579:Patient Selection; D014700:Verapamil / Q000627:therapeutic use
D000959:Antihypertensive Agents; D001786:Blood Glucose; D007211:Indoles; C052035:trandolapril; D014700:Verapamil