Diuretics, Beta-Blockers, and Statins and Risk of Diabetes
Diuretics, Beta-Blockers, and Statins and Risk of Diabetes
Objective To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes.
Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.
Setting NAVIGATOR trial.
Participants Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5,640), diuretics (n=6,346), statins (n=6,146), and calcium channel blockers (n=6,294). Use of calcium channel blocker was used as a metabolically neutral control.
Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment.
Results During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1,353 (22.0%), and calcium channel blockers in 1,171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively).
Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant.
Trial registration ClinicalTrials.gov NCT00097786.
Use of β blockers, diuretics, and statins has been established to reduce cardiovascular morbidity and mortality in a variety of diseases. However, although statins reduce cardiovascular events and mortality in patients with coronary artery disease or equivalent risk factors, debate continues about their role in primary prevention in lower risk populations.
Despite the overwhelming benefits of these drugs on cardiovascular outcomes, recent evidence suggests that long term use may increase the risk of diabetes. Large trials examining cardiovascular outcomes and mortalities suggested an increased incidence of new onset diabetes with long term use of diuretics. Likewise, other studies have reported an increased incidence of diabetes in people treated with statins, prompting the US Food and Drug Administration to release a safety label change in 2012. Furthermore, β blockers have been implicated in impaired glucose metabolism, especially with diuretics.
Large scale studies with serial glucose measurements examining the association between these drugs and new onset diabetes in patients with impaired glucose tolerance are limited. We reanalysed data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study to examine the relation between risk of new onset diabetes and use of β blockers, thiazide diuretics, or statins in treatment naïve patients.
Abstract and Introduction
Abstract
Objective To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes.
Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial.
Setting NAVIGATOR trial.
Participants Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5,640), diuretics (n=6,346), statins (n=6,146), and calcium channel blockers (n=6,294). Use of calcium channel blocker was used as a metabolically neutral control.
Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment.
Results During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1,353 (22.0%), and calcium channel blockers in 1,171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively).
Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant.
Trial registration ClinicalTrials.gov NCT00097786.
Introduction
Use of β blockers, diuretics, and statins has been established to reduce cardiovascular morbidity and mortality in a variety of diseases. However, although statins reduce cardiovascular events and mortality in patients with coronary artery disease or equivalent risk factors, debate continues about their role in primary prevention in lower risk populations.
Despite the overwhelming benefits of these drugs on cardiovascular outcomes, recent evidence suggests that long term use may increase the risk of diabetes. Large trials examining cardiovascular outcomes and mortalities suggested an increased incidence of new onset diabetes with long term use of diuretics. Likewise, other studies have reported an increased incidence of diabetes in people treated with statins, prompting the US Food and Drug Administration to release a safety label change in 2012. Furthermore, β blockers have been implicated in impaired glucose metabolism, especially with diuretics.
Large scale studies with serial glucose measurements examining the association between these drugs and new onset diabetes in patients with impaired glucose tolerance are limited. We reanalysed data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study to examine the relation between risk of new onset diabetes and use of β blockers, thiazide diuretics, or statins in treatment naïve patients.
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