Thiazide diuretics and risk of diabetes mellitus

• in the ALLHAT study, the first-line use of a thiazide diuretic, an angiotensin-converting enzyme (ACE) inhibitor, or a calcium-channel blocker (CCB) for hypertension was similarly effective in reducing the risk of major cardiovascular (CV) events
  • CCBs were less effective in preventing heart failure than thiazide diuretics, whereas development of diabetes (defined as fasting blood glucose levels [FGs] above 6.9mmol/l) was more frequent with thiazide diuretics than with CCBs
  • a post-hoc subgroup analysis considered non-diabetic patients in ALLHAT who were randomised to initially receive chlortalidone (n=8,419), amlodipine (n=4,958), or lisinopril (n=5,034) (2)
    • after two years, mean FGs were raised in all groups — by 0.47mmol/l, 0.31mmol/l and 0.19mmol/l, respectively
    • more cases of incident diabetes, when defined by a 6.9mmol/l FG threshold, were detected in the chlortalidone group - however, absolute differences between groups in incident diabetes were small (chlortalidone 9.3%, amlodipine 7.2%, lisinopril 5.6%)
      • risk of developing diabetes was lower for lisinopril (odds ratio [OR] 0.55, 95%CI 0.43 to 0.70, P<0.001) or amlodipine (OR 0.73, 95%CI 0.58 to 0.91, P=0.008) compared with chlortalidone
      • was no significant association between FG changes at two years and any of the study endpoints (death, CV disease or end-stage renal disease), whether analysed for all treatments combined or for chortalidone alone
    • findings support the results from the 14-year follow-up of SHEP (3) and suggest that, even if diabetes does occur during the treatment of hypertension with thiazide diuretics, this does not create any greater cardiovascular risk
      • possible that that the raised FGs that occur with thiazide diuretics arise from mechanisms that are different from those associated with diabetes in other circumstances (4)

Thiazide diuretics or CCBs are considered by NICE as equal first-line choices for people who are black (i.e. of African or Caribbean descent, not mixed race, Asian or Chinese) or aged 55 years or older (5):

• NICE suggests that the choice between thiazide diuretics and CCBs should be made by the clinician and patient, using careful clinical judgement about the patient’s risk of adverse effects and consideration of the patient’s preference

Reference:

1. The ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic. JAMA 2002;288:2981–97
2. Barzilay JI et al.. ALLHAT Collaborative Research Group. Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment. Arch Intern Med 2006;166:2191–201.
3. Kostis JB et al. Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes. Am J Cardiol 2005;95:29–35.
4. MeReC Extra March 2007.
5. MeReC Bulletin 2006;17:1–20.