Essential hypertension ( DIME ) study diuretics : Diuretics In the Management of hypertensive patients receiving thiazide evaluation of risk for type 2 diabetes in A randomised controlled trial for the for the DIME Investigators

Correspondence to Dr Shinichiro Ueda; blessyou@med.u-ryukyu.ac.jp ABSTRACT Objectives: Thiazide diuretics are one of the first choice antihypertensives but not optimally utilised because of concerns regarding their adverse effects on glucose metabolism. The Diuretics In the Management of Essential hypertension (DIME) study was designed, for the first time, to assess the risk for type 2 diabetes mellitus in patients with essential hypertension during antihypertensive treatment with low-dose thiazide diuretics compared to those not treated with diuretics. Design: Multicentre, unblinded, pragmatic, randomised, controlled trial with blinded assessment of end points and intention-to-treat analysis that was started in 2004 and finished in 2012. Setting: Hypertension clinics at 106 sites in Japan, including general practitioners’ offices and teaching hospitals. Participants: Non-diabetic patients with essential hypertension. Interventions: Antihypertensive treatment with lowdose thiazide diuretics at 12.5 mg/day of hydrochlorothiazide or equivalent (Diuretics group) or that without thiazide diuretics (No-diuretics group). Main outcome: The primary outcome was new onset of type 2 diabetes diagnosed according to WHO criteria and the criteria of Japanese Society of Diabetes. Results: 1130 patients were allocated to Diuretics (n=544) or No-diuretics group (n=586). Complete end point information was collected for 1049 participants after a median follow-up of 4.4 years. Diabetes developed in 25 (4.6%) participants in the Diuretics group, as compared with 29 (4.9%) in the No-diuretics group (HR 0.93; 95% CI 0.55 to 1.58; p=0.800). Conclusions: Antihypertensive treatment with thiazide diuretics at low doses may not be associated with an increased risk for new onset of type 2 diabetes. This result might suggest safety of use of low doses of thiazide diuretics. Trial registration number: ClinicalTrials.gov NCT00131846. INTRODUCTION Antihypertensive treatment with thiazide diuretics effectively reduces cardiovascular risk in hypertensive patients and there has been evidence to suggest no inferiority when compared to ‘newer’ antihypertensive drugs. However, concern remains regarding adverse effects of diuretics on glucose metabolism and the prognostic implications of such effects on cardiovascular events. 7 The diabetogenic effect of diuretics seems to be taken for granted. In fact, in addition to results from a large cohort study, a recent network meta-analysis conclusively showed a higher risk for new onset of type 2 diabetes in patients receiving thiazide diuretics than in those receiving calcium antagonists, ACE inhibitors, angiotensin receptor blockers (ARB) or placebo. It is of note, however, that relatively high doses of thiazide diuretics (25 mg of hydrochlorothiazide equivalent or more) were used mainly with β-blockers in most studies included in this meta-analysis. Antihypertensive treatment with diuretics in this way is no longer relevant to current antihypertensive therapeutic practice. Thiazide Strengths and limitations of this study