Article type
Year
Abstract
Background: Concern has arisen from recent trials that combining beta-blockers
and thiazide-type diuretics to treat hypertension may lead to an increased incidence of diabetes mellitus. Pharmacologically this is plausible since beta-blockers increase insulin resistance and thiazide diuretics reduce insulin secretion.
Objective: To test the null hypothesis than a combination of a thiazide-type diuretic and beta blocker does not increase the risk of new-onset diabetes by secondary analysis of published RCTs.
Methods: Hypertension treatment trials were included in the analysis that: i) featured an arm beginning with a thiazide diuretic or beta-blocker and subsequently added the other drug when necessary; ii) assessed cardiovascular outcomes; iii) reported new-onset diabetes; and, iv) featured at least one-year duration. Two reviewers independently selected studies and abstracted data from medical database and published review searches. Patients with diabetes at enrolment were excluded from trial denominators.
Results: Seven trials met the inclusion criteria including nearly 77,000 patients and over 340,000 patient years of follow-up. Meta-analysis of available trials suggests that patients exposed to treatment regimens combining thiazide (or thiazide-like) diuretics and beta-blockers are at greater risk of developing diabetes than regimens avoiding this combination (risk ratio for alternative therapy: 0.81, 95%CI: 0.77 to 0.86; Q; p=0.17). This amounts to one additional case of diabetes per 500 patients treated per year with this combination. The nature of the analysis supports the interpretation that the combination rather than the individual drugs may be the problem. The findings are vulnerable to confounding and reporting bias although the analysis appears robust and pharmacologically plausible.
Conclusions: The balance of benefit and harm suggests that the routine combined use of a thiazide diuretic with a beta-blocker may need to be avoided in the early management of hypertension. Authorities developing national guidelines may wish to respond to this data by issuing guidance to clinicians to manage change. Secondary, patient level meta analysis of trials in hypertension that have involved thiazide diuretics and beta-blockers would more reliably inform this issue.
Acknowledgements: The work was funded as part of ongoing work for the National Institute for Clinical Excellence (NICE).
and thiazide-type diuretics to treat hypertension may lead to an increased incidence of diabetes mellitus. Pharmacologically this is plausible since beta-blockers increase insulin resistance and thiazide diuretics reduce insulin secretion.
Objective: To test the null hypothesis than a combination of a thiazide-type diuretic and beta blocker does not increase the risk of new-onset diabetes by secondary analysis of published RCTs.
Methods: Hypertension treatment trials were included in the analysis that: i) featured an arm beginning with a thiazide diuretic or beta-blocker and subsequently added the other drug when necessary; ii) assessed cardiovascular outcomes; iii) reported new-onset diabetes; and, iv) featured at least one-year duration. Two reviewers independently selected studies and abstracted data from medical database and published review searches. Patients with diabetes at enrolment were excluded from trial denominators.
Results: Seven trials met the inclusion criteria including nearly 77,000 patients and over 340,000 patient years of follow-up. Meta-analysis of available trials suggests that patients exposed to treatment regimens combining thiazide (or thiazide-like) diuretics and beta-blockers are at greater risk of developing diabetes than regimens avoiding this combination (risk ratio for alternative therapy: 0.81, 95%CI: 0.77 to 0.86; Q; p=0.17). This amounts to one additional case of diabetes per 500 patients treated per year with this combination. The nature of the analysis supports the interpretation that the combination rather than the individual drugs may be the problem. The findings are vulnerable to confounding and reporting bias although the analysis appears robust and pharmacologically plausible.
Conclusions: The balance of benefit and harm suggests that the routine combined use of a thiazide diuretic with a beta-blocker may need to be avoided in the early management of hypertension. Authorities developing national guidelines may wish to respond to this data by issuing guidance to clinicians to manage change. Secondary, patient level meta analysis of trials in hypertension that have involved thiazide diuretics and beta-blockers would more reliably inform this issue.
Acknowledgements: The work was funded as part of ongoing work for the National Institute for Clinical Excellence (NICE).