Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

Lan Shen, Bimal R Shah, Eric M Reyes, Laine Thomas, Daniel Wojdyla, Peter Diem, Lawrence A Leiter, Bernard Charbonnel, Viacheslav Mareev, Edward S Horton, Steven M Haffner, Vladimir Soska, Rury Holman, M Angelyn Bethel, Frank Schaper, Jie-Lena Sun, John J V McMurray, Robert M Califf, Henry Krum, Lan Shen, Bimal R Shah, Eric M Reyes, Laine Thomas, Daniel Wojdyla, Peter Diem, Lawrence A Leiter, Bernard Charbonnel, Viacheslav Mareev, Edward S Horton, Steven M Haffner, Vladimir Soska, Rury Holman, M Angelyn Bethel, Frank Schaper, Jie-Lena Sun, John J V McMurray, Robert M Califf, Henry Krum

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=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). 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 1353 (22.0%), and calcium channel blockers in 1171 (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.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: BRS served as a consultant for Cardinal Health and Castlight Health. PD received consulting fees, honoraria and research support from Novartis. LAL received honorariums or research support from Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, Merck, Novartis, Novo Nordisk, Sanofi, Servier, and Takeda. BC received fees for consultancy, speaking, travel, or accommodation from AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim, GlaxoSmithKline, Janssen, Eli Lilly, Merck-Sharp & Dohme, Novartis, Novo Nordisk, Roche, Sanofi-Aventis, and Takeda. ESH received honorariums from Novartis for service on committees and advisory boards, including the design and conduct of the NAVIGATOR trial and the NAVIGATOR trial publications committee. SMH served on the executive committee for the NAVIGATOR trial (received honorariums from Novartis). RH received research funding from Novartis. MAB received research support from Novartis and Bayer. Her department has received research funding from Merck, Amylin, Eli Lilly, and Bristol-Myers Squibb. All disclosures for RMC are available at www.dcri.org/about-us/conflict-of-interest/Califf-COI_2012.pdf. HK was a member of the NAVIGATOR Steering Committee.

Figures

https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4793423/bin/shel011154.f1_default.jpg
Patients enrolled in NAVIGATOR trial and their use of drugs of interest at baseline. CCB=calcium channel blocker. Cohorts are not mutually exclusive but may receive other drugs

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Source: PubMed

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