Association of Thiazide Diuretics With Diabetes Progression, Kidney Disease Progression, Cardiovascular Outcomes, and Death Among Patients With Diabetes Who Initiate Statins.

Statins have been associated with diabetes mellitus (DM) progression but their cardiovascular benefit in patients with DM outweigh the harm. However, the effects of concurrent use of other medications that similarly increase blood glucose level, such as thiazide diuretics, are not well studied. This study aimed to evaluate the association of concurrent use of thiazide diuretics and statins on DM progression, cardiovascular and renal outcomes, and death in patients with DM. This is a retrospective cohort study of Veterans with DM who initiated statins between 2003 and 2015. The cohort comprised thiazide users (concomitantly used thiazides and statins for ≥6 months) and active comparators (concomitantly used calciun channel blockers [CCB] but not thiazides and statins for ≥6 months). We excluded patients who were <18 years old, with chronic kidney disease stage 4 or worse, or used loop diuretics. We propensity-score-matched comparison groups on 99 baseline characteristics including demographics, healthcare utilization, co-morbidities, cardiovascular and co-morbidity scores, vital signs, laboratory data, and medication class usage. Outcomes were: (1) DM progression (new insulin initiation, increase in the number of glucose-lowering medication classes, and hyperglycemic episodes); (2) kidney disease progression (doubling of serum creatinine, incidence of chronic kidney disease stage 5, initiation of renal replacement therapy, and incidence of diabetic nephropathy); (3) cardiovascular outcomes (acute myocardial infarction, stroke, cardiac arrest); and (4) total mortality. From 297,967 statin users (228,509 Thiazide-statin users and 69,458 active comparators), we successfully matched 67,614 pairs. In comparison to active comparators, thiazide-statin users had increased risk of DM progression (65.6% in CCB group vs 68.1% in thiazide group; odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.09 to 1.15), decreased risk of kidney progression (16.9% in CCB group vs 16.5 in thiazide group; OR: 0.97, 95% CI: 0.94 to 0.99), decreased risk of cardiovascular outcomes (15.7% in CCB group vs 14.6% in thiazide group; OR: 0.92, 95% CI: 0.89 to 0.95), and similar risk of total mortality (19.7% in each group; OR: 1.00, 95% CI: 0.98 to 1.03). This study attempted to answer an important clinical question whether thiazide diuretics should be discontinued or substituted upon statin initiation. Our results showed that concurrent use of statin and thiazides in patients with DM was associated with DM progression but with less kidney progression and cardiovascular outcomes and no difference in mortality. Clinicians should closely monitor DM control when thiazides and statins are used concurrently.
Competing Interests: Declaration of Competing Interest Ishak Mansi was supported by Orlando VA Healthcare System. Dr. Alvarez was supported by NIH grant (UL1TR003163). Dr. Alvarez has received research funding from Merck, Boehringer Ingelheim, and Bristol Myers Squibb not related to this project. The other authors have no conflicts of interest to declare. The views expressed herein are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, Veterans Affairs Administration, or the United States Government, Hospital Corporation of America Healthcare, or any of its affiliated entities. Some of the authors are employees of the United States government. This work was prepared as part of their official duties and, as such, there is no copyright to be transferred. This research was supported in part by HCA Healthcare and/or an HCA Healthcare affiliated entity. The views expressed in this publication represent those of the author(s) and do not necessarily represent the official views of HCA Healthcare or any of its affiliated entities.
(Published by Elsevier Inc.)