Antihypertensive Medications and the Risk of Incident Type 2 Diabetes: Response to Taylor et al.

Taylor et al. (1) reported that antihypertensive regimens containing either β-blockers or thiazide diuretics confer a greater risk of new diabetes when compared with ACE inhibitors or calcium channel blockers (CCBs). However, we feel that the interpretation of data provided by the authors warrants further discussion. It is unclear what medication classes were included in the “other” category for each cohort. The Nurse’s Health Study (NHS) I (2) suggests a protective effect for ACE inhibitors, since the risk of diabetes is higher for patients on thiazides, β-blockers, “other” antihypertensives, and CCBs. In NHS II (2), for which more limited information was collected (only thiazides and “other”), the relative risk of new diabetes in the “other” group was significant and comparable to thiazides. In the all-male Health Professionals Follow-up Study (3), when information on CCBs and β-blockers was collected, the relative risk for “other” antihypertensives was no longer significant. Hence, we speculate that the “other” medications in NHS I and II may have been diabetogenic, and men on “other” medications in Health Professionals Follow-Up Study were protected from new diabetes by the addition of ACE inhibitors or CCBs or by other unknown mechanisms. Did male/female differences contribute to the incidence of new diabetes in these three studies instead of medications alone?

It is still debated whether thiazides and β-blockers promote diabetes and whether ACE inhibitors and CCBs are antidiabetogenic (4). The lack of prospective clinical trials evaluating the incidence of diabetes as a primary end point and the absence of placebo-controlled studies leaves physicians wondering whether a particular antihypertensive medication causes or prevents diabetes. However, Taylor et al. (1) have opened a new avenue in clinical research, providing preliminary evidence for the increased risk of new diabetes with the use of thiazides and β-blockers in men but not in women. This study also raises the possibility of male/female differences in relation to the effects of ACE inhibitors and CCBs in the prevention of new diabetes.