Comparison of Effects of Olmesartan and Telmisartan on Blood Pressure and Metabolic Parameters in Japanese Early-Stage Type-2 Diabetics with Hypertension

7 Hypertens Res Vol.31 (2008) No.1 p.7-13 Original Article Comparison of Effects of Olmesartan and Telmisartan on Blood Pressure and Metabolic Parameters in Japanese Early-Stage Type-2 Diabetics with Hypertension Shiho NAKAYAMA1), Hirotaka WATADA1), Tomoya MITA1), Fuki IKEDA1), Tomoaki SHIMIZU1), Hiroshi UCHINO1), Yoshio FUJITANI1),2), Takahisa HIROSE1),2), and Ryuzo KAWAMORI1),2) Angiotensin II type-1 receptor blockers (ARBs) are regarded as first-line treatments for type-2 diabetes with hypertension. Despite the availability of various types of ARBs, there are no comparative studies of their effects on patients with diabetes. In this open-label prospective crossover study, we compared the effects of olmesartan (20 mg/day) and telmisartan (40 mg/day). Twenty Japanese early-stage type-2 diabetes patients with hypertension treated with valsartan (80 mg/day) for at least 8 weeks were recruited to this study. At study entry, valsartan was changed to olmesartan (20 mg/day) or telmisartan (40 mg/day) and administered for 8 weeks. The drugs were then switched and treatment was continued for another 8 weeks. We analyzed the blood pressure lowering effects of each drug by 24-h ambulatory blood pressure monitoring at 0, 8, and 16 weeks. Simultaneously, we measured metabolic parameters and inflammation markers. Olmesartan lowered mean systolic and diastolic blood pressure more significantly than did telmisartan. While there were no differences between the groups in metabolic parameters, including HbA1c and adiponectin, the decreases in serum interleukin-6 and highly sensitive C-reactive protein were more significant by olmesartan treatment. Our results indicate that olmesartan has more potent arterial blood pressure lowering and anti-inflammatory effects than telmisartan. (Hypertens Res 2008; 31: 7–13) Key Words: angiotensin, hypertension, type-2 diabetes, inflammation, peroxisome proliferation–activated receptor γ Introduction Patients with type-2 diabetes are at high risk for developing cardiovascular diseases, which are also the most common cause of death in these patients. In type-2 diabetes, the prevalence of hypertension is higher than in the general population (1). Hypertension complicated with diabetes increases the incidence of cardiovascular disease (2). Thus, to reduce car- diovascular events in patients with type-2 diabetes, treatment of hypertension in addition to glycemic control is important (2, 3). The importance of strict blood pressure control in patients with type-2 diabetes was emphasized in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) (4). The report recommends a blood pressure target of < 140/90 mmHg for most patients with uncomplicated hypertension. On the other hand, the report and the Japanese Soci- From the 1)Department of Medicine, Metabolism, and Endocrinology and 2)Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo, Japan. Address for Reprints: Hirotaka Watada, M.D., Department of Medicine, Metabolism, and Endocrinology, Juntendo University School of Medicine, 2–1– 1 Hongo, Bunkyo-ku, Tokyo 113–8421, Japan. E-mail: Received March 23, 2007; Accepted in revised form July 25, 2007. 8 Hypertens Res Vol. 31, No. 1 (2008) -8 W 0W 16 W 8W Run-in period Treatment period Olmesartan (20 mg/day) Telmisartan (40 mg/day) Telmisartan (40 mg/day) Olmesartan (20 mg/day) Valsartan (80 mg/day) ABPM ABPM ABPM Blood sample Blood sample Blood sample Fig. 1. Study protocol. The study protocol is shown in this schematic diagram. Blood sampling and ABPM were performed at week 0 for basal data. Blood samples obtained at week 8 or week 16 were used for evaluation of each drug. W, week. ety of Hypertension (5) also recommends < 130/80 mmHg for hypertensive patients with diabetes mellitus. Angiotensin II type-1 receptor blockers (ARB) are widely used for the treatment of hypertension (6). They also have beneficial effects on hypertension-related cardiovascular endorgan damage, at least in part through a reduction of oxidative stress and inflammation (7, 8). In addition, they substantially lower the risk of type-2 diabetes compared with other antihypertensive therapies, probably by regulating insulin sensitivity (9, 10). Among the several ARBs available in the clinical setting, olmesartan is thought to have a significantly stronger blood pressure lowering effect than losartan or valsartan with their respective starting doses (11, 12). In addition, recent data demonstrated that olmesartan more adequately achieved ambulatory blood pressure monitoring (ABPM) goals during the early morning surge period than did candesartan (13). Considering the importance of strict blood pressure control (14), olmesartan offers certain advantages in clinical use. With regard to its metabolic effect, telmisartan has the unique property of selective peroxisome proliferation–activated receptor γ (PPARγ)–modulating activity, at least in vitro (15–17). Thus, telmisartan might have clinical effects similar to those of PPARγ agonists, such as improving insulin resistance and increasing serum adiponectin levels. In fact, a recent study demonstrated that replacement of valsartan with telmisartan reduced serum highly sensitive C-reactive protein (hs-CRP) and increased serum adiponectin (18). Another study revealed that telmisartan has superior effects on metabolic parameters compared to losartan in hypertensive patients with metabolic syndrome (19). In addition, telmisar- tan’s blood pressure lowering effect is reported to last longer than valsartan’s (20). To gain insight into the respective properties of ARB for type-2 diabetic patients with hypertension, an open-label crossover trial was conducted to compare the efficacy of the starting doses of olmesartan and telmisartan on blood pressure, metabolic parameters, and inflammatory parameters. Methods Subjects All patients with type-2 diabetes mellitus who visited Juntendo University Hospital (Tokyo, Japan) or Secomedic Hospital (Funabashi, Japan) from March 2006 to August 2006 were asked to participate in the study. The inclusion criteria were patients with type-2 diabetes mellitus and hypertension who were being treated with valsartan 80 mg once daily for at least 8 weeks. Patients with HbA1c exceeding 7.0% and/or patients treated with insulin or more than a minimal dose of sulfonylurea agents were excluded from the study. In addition, patients with diabetic microangiopathy, severe renal or hepatic disease, overt cardiovascular disease, or malignancy were excluded. A total of 20 Japanese subjects were recruited for this study. The hospital ethics committee approved this study protocol, and informed consent was obtained from each subject. Study Design An open-label crossover design was used. After completion Nakayama et al: Comparison of Olmesartan and Telmisartan Table 1. Baseline Characteristi (...truncated)