Journal of Human Hypertension (2011) 25, 346–353 & 2011 Macmillan Publishers Limited All rights reserved 0950-9240/11 www.nature.com/jhh ORIGINAL ARTICLE Olmesartan/amlodipine vs olmesartan/ hydrochlorothiazide in hypertensive patients with metabolic syndrome: the OLAS study FJ Martinez-Martin1, H Rodriguez-Rosas2, I Peiro-Martinez3, P Soriano-Perera4, P Pedrianes-Martin2 and C Comi-Diaz2 1Outpatient Hypertension Clinic, Hospital Universitario Dr. Negrin, Barranco de la Ballena, Las Palmas de Gran Canaria, Spain; 2Endocrinology and Nutrition Department, Hospital Universitario Dr. Negrin, Barranco de la Ballena, Las Palmas de Gran Canaria, Spain; 3Servei d’Endocrinologia i Nutricio´, Hospital Universitari de Bellvitge, Fexia Long sn, Barcelona, Spain and 4Endocrinology Department, Hospital Universitario de Canarias Carretera Cuesta Taco, San Cristobal De La Laguna (Tenerife), Spain We studied the effects of treatment with olmesartan/ amlodipine and olmesartan/hydrochlorothiazide on inflammatory and metabolic parameters (including new-onset diabetes as a secondary endpoint) in non- diabetic hypertensive patients with metabolic syndrome (MetS). A total of 120 patients with MetS and stage I and II hypertension were randomized to olmesartan 20 mg/amlodipine 5 mg or olmesartan 20 mg/hydrochlor- othiazide 12.5 mg. If target systolic blood pressure (o140 mm Hg) was not reached, doses were doubled after 13 weeks; doxazosin 4 mg was added after 26 weeks, and doubled after 39 weeks; follow-up ended at 78 weeks. At each visit, blood pressure (BP), fasting plasma glucose, insulin, adiponectin, tumour necrosis factor-a, C-reactive protein (CRP), intercellular adhesion molecule-1, vascular cell adhesion molecule-1, interleu- kins-1b, -6 and -8, and albuminuria were measured; BP was similarly reduced in both groups; 80% of patients reached target BP. Reductions in albuminuria were also similar (50%). Only olmesartan/amlodipine reduced the insulin resistance index (24%, Po0.01), increased plasma adiponectin (16%, Po0.05) and significantly reduced all of the inflammation markers studied, except CRP, which showed a similar reduction in each group. The risk of new-onset diabetes was signi- ficantly lower with olmesartan/amlodipine (P ¼ 0.02). Both olmesartan-based combinations were effective, but the amlodipine combination resulted in metabolic and anti-inflammatory effects that may have advantages over the hydrochlorothiazide combination. Journal of Human Hypertension (2011) 25, 346–353; doi:10.1038/jhh.2010.104; published online 25 November 2010 Keywords: metabolic syndrome; olmesartan; amlodipine; hydrochlorothiazide; type 2 diabetes mellitus Introduction The prevalence of metabolic syndrome (MetS) in patients with essential hypertension is very high, and has been estimated as being close to 50%.1 Hypertensive patients with MetS have a much higher cardiovascular (CV) risk than their counter- parts without MetS,2 and also have a particularly high risk of developing type 2 diabetes mellitus (T2DM).3 In addition, the choice of antihypertensive therapy can have a large impact on the risk of development of T2DM.4 Renin–angiotensin system Correspondence: Dr FJ Martinez-Martin, Outpatient Hypertension Clinic, Hospital Universitario Dr. Negrin, Barranco de la Ballena, Las Palmas de Gran Canaria 35020, Spain. E-mail: dr.j.martinez@gmail.com Received 24 April 2010; revised 28 September 2010; accepted 25 October 2010; published online 25 November 2010 blockers, that is, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ARBs), improve insulin sensitivity and reduce the risk of developing T2DM compared with placebo, whereas calcium channel blockers (CCBs) have a neutral effect. Thiazide diuretics and b-blockers decrease insulin sensitivity and increase the incidence of T2DM.4 Therefore, the combination of an ARB and a CCB might be particularly beneficial in patients with high metabolic risk.5 The present European Guidelines for the Manage- ment of Hypertension acknowledge that most high- risk hypertensive patients require a combination of antihypertensive drugs.6 For patients with MetS, the recommended combinations are renin–angiotensin system blockers combined with low-dose thiazide diuretics or CCBs.6 In spite of the well-known effect of antihypertensive treatment on glucose and lipid metabolism, few studies have been conducted