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Antihypertensive Therapy and Incidence of Type 2 Diabetes

A systematic review

¹ Division of General Internal Medicine, University of Alberta, Edmonton, Alberta, Canada
² The Institute for Clinical Evaluative Sciences, Toronto, Ontario, Canada
³ Faculty of Medicine and Department of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
⁴ Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada

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}ualberta.ca

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 Abstracts were not included, and unpublished studies were not sought.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 ß-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.

Abbreviations: ALLHAT, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial • ALPINE, Antihypertensive Treatment and Lipid Profile in a North of Sweden Efficacy Evaluation • CAPPP, Captopril Prevention Project • CHARM, Candesartan in Heart Failure Assessment of Reduction in Mortality and Morbidity • EWPHE, European Working Party on High Blood Pressure in the Elderly • HAPPHY, Heart Attack Primary Prevention in Hypertension • HOPE, Heart Outcomes Prevention Evaluation Trial • IFG, impaired fasting glucose • IGT, impaired glucose tolerance • INSIGHT, Intervention as a Goal in Hypertension • NORDIL, Nordic Diltiazem • SCOPE, Study on Cognition and Prognosis in the Elderly • SHEP, Systolic Hypertension in the Elderly Program

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