This study investigated the adverse metabolic effects (AMEs) of atenolol and hydrochlorothiazide (HCTZ) among hypertensive patients with and without abdominal obesity in the Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR) Study. From this randomized, open-label study, 395 patients without a history of heart disease or diabetes mellitus were included. The investigators found that the AMEs associated with both drugs were observed within 9 weeks of initiation and were more pronounced in patients with abdominal obesity with longer duration of exposure to HCTZ. Participants with abdominal obesity (58% of the study population) presented higher baseline values for glucose, insulin, triglycerides, lower HDL values, and a greater prevalence of metabolic syndrome compared to patients without abdominal obesity. Moreover, hypertensive patients with abdominal obesity, exposed to HCTZ alone or in combination with atenolol, had a significantly increased glucose, insulin, HOMA-IR and triglyceride levels as well as increased frequency of impaired glucose tolerance during follow-up. New onset-diabetes mellitus occurred in 13 patients (6%) with and in 4 patients (2%) without abdominal obesity. These findings reinforce the recommendation to prescribe these medications with caution for patients with abdominal obesity who are at risk of developing metabolic syndrome and diabetes mellitus. In their comment, Manrique C et al. describe very well the mechanisms by which HCTZ and β-blockers may impair glucose metabolism in hypertensive patients with abdominal obesity. Moreover, they report studies of new vasodilating β-blockers which do not appear to cause negative metabolic effects.
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