Antihypertensive Therapy and Incidence of Type 2 Diabetes

A systematic review

  1. Raj Padwal, MD, FRCP1 and
  2. Andreas Laupacis, MD, FRCP234
  1. 1Division of General Internal Medicine, University of Alberta, Edmonton, Alberta, Canada
  2. 2The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
  3. 3Faculty of Medicine and Department of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
  4. 4Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada
  1. Address correspondence and reprint requests to Raj Padwal, Division of General Internal Medicine, University of Alberta Hospital, 2E3 Walter C. Mackenzie Health Sciences Center, Edmonton, AB, Canada T6G 2B7. E-mail: rpadwal{at}


OBJECTIVE—To systematically review the available evidence examining the effects of the major antihypertensive drug classes on the incidence of type 2 diabetes.

RESEARCH DESIGN AND METHODS—The Cochrane Controlled Trials Register, Medline, and Embase were searched for English-language case-control, cohort, and randomized controlled trials involving the major antihypertensive classes and reporting type 2 diabetes as an end point. Reference lists of original studies and narrative reviews were also hand searched. One reviewer (R.P.) performed the electronic searches. Both reviewers independently extracted data and assessed all potentially relevant studies for inclusion and methodological quality. Abstracts were not included, and unpublished studies were not sought.

RESULTS—One case-control study, 8 cohort studies, and 14 randomized controlled trials met inclusion criteria. No study examined diabetes incidence as a primary end point. Poor methodological quality limits the conclusions that can be drawn from most nonrandomized trials. Evidence from randomized studies is also potentially limited by several sources of bias, including treatment contamination and bias inherent in post hoc analyses. Data from the highest-quality studies suggest that diabetes incidence is unchanged or increased by thiazide diuretics and β-blockers and unchanged or decreased by ACE inhibitors, calcium channel blockers, and angiotensin receptor blockers.

CONCLUSIONS—The major antihypertensive classes may exert differential effects on diabetes incidence, although current data are far from conclusive. Ongoing placebo-controlled randomized trials involving potentially beneficial drug classes and examining diabetes incidence as a primary end point should provide more definitive evidence.


  • A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    • Accepted September 22, 2003.
    • Received July 2, 2003.
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