Comparison of effects of azelnidipine and trichlormethiazide in combination with olmesartan on blood pressure and metabolic parameters in hypertensive type 2 diabetic patients.
Aims/Introduction:  Angiotensin II type 1 receptor blockers (ARB) are regarded as first-line treatment for type 2 diabetes with hypertension. However, lowering blood pressure to the target level often requires more than one antihypertensive agent as recommended by the guideline. In this open-label, prospective, crossover clinical trial, we compared the effects of combination treatment of ARB with a calcium channel blocker (CCB) or with a low-dose thiazide diuretic on blood pressure (BP) and various metabolic parameters in hypertensive patients with type 2 diabetes.


METHODS
A total of 39 Japanese type 2 diabetics with hypertension treated with olmesartan (20 mg/day) for at least 8 weeks were recruited to this study. At study entry, treatment was switched to either olmesartan (20 mg/day)/azelnidipine (16 mg/day) or olmesartan (20 mg/day)/trichlormethiazide (1 mg/day) and continued for 12 weeks. Then, the drugs were switched and treatment was continued for another 12 weeks. We measured clinical blood pressure and various metabolic parameters before and at the end of each study arm.


RESULTS
Compared with the olmesartan/trichlormethiazide treatment, treatment with olmesartan/azelnidipine achieved superior clinical blood pressure and pulse rate control. In contrast, the treatment with olmesartan/trichlormethiazide resulted in increased HbA1c, serum uric acid and worsening of estimated glomerular filtration rate, though there were no differences in other metabolic parameters including urine 8-hydroxy-2'-deoxyguanosine, C-reactive protein and adiponectin between the two treatments.


CONCLUSIONS
Our results show that the combination of ARB with azelnidipine is more beneficial with regard to blood pressure control and metabolic outcome than the combination of olmesartan with low dose trichlormethiazide. This trial was registered with UMIN clinical trial registry (no. UMIN000005064). (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00135.x, 2011).
Department of Medicine, Diabetes and Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center.
Hidenori
H
Yoshii
Department of Medicine, Metabolism and Endocrinology.
Tomoya
T
Mita
Division of Metabolism and Endocrinology, Department of Internal Medicine, Juntendo Urayasu Hospital, Urayasu.
Junko
J
Sato
Division of Metabolism and Endocrinology, Department of Internal Medicine, Juntendo Urayasu Hospital, Urayasu.
Yuuki
Y
Kodama
Department of Diabetes and Endocrinology, Juntendo University Shizuoka Hospital, Shizuoka, Japan.
Jong Bock
JB
Choi
Department of Medicine, Metabolism and Endocrinology.
Koji
K
Komiya
Department of Medicine, Diabetes and Endocrinology, Juntendo University Nerima Hospital, Tokyo.
Kazuhisa
K
Matsumoto
Department of Medicine, Metabolism and Endocrinology.
Rei
R
Kanno
Department of Medicine, Diabetes and Endocrinology, Juntendo University Nerima Hospital, Tokyo.
Masahiko
M
Kawasumi
Division of Metabolism and Endocrinology, Department of Internal Medicine, Juntendo Urayasu Hospital, Urayasu.
Hajime
H
Koyano
Department of Medicine, Metabolism and Endocrinology.
Takahisa
T
Hirose
Department of Medicine, Diabetes and Endocrinology, Juntendo Tokyo Koto Geriatric Medical Center.
Tomio
T
Onuma
Sportology Center.
Ryuzo
R
Kawamori
Department of Medicine, Metabolism and Endocrinology ; Sportology Center ; Center for Therapeutic Innovations in Diabetes ; Center for Beta Cell Biology and Regeneration, Juntendo University Graduate School of Medicine.
Hirotaka
H
Watada
Angiotensin II type 1 receptor blockers; Calcium channel blocker; Thiazide diuretic