USA: Concurrent Use of Statin and Thiazides in Patients with Diabetes Mellitus

Concurrent use of statin and thiazides in patients with diabetes mellitus (DM) was associated with DM progression, but with less kidney progression and cardiovascular (CV) outcomes and no difference in mortality, a recent study published in The American Journal of Cardiology has found.

"When thiazides and statins are used concurrently, clinicians should closely monitor diabetes mellitus control," Hesham Afify, University of Louisville Medical Center, Louisville, Kentucky, and colleagues wrote in their study.

Previous studies have shown statins to be associated with diabetes progression but their CV benefit in DM patients outweigh the harm. However, there has been no clear understanding of the effects of concurrent use of other medications that similarly raise blood glucose levels, such as thiazide diuretics.

To clarify the same, Afify and the team aimed to evaluate the association of concurrent use of thiazide diuretics and statins on the progression of diabetes mellitus, renal and cardiovascular outcomes, and death in patients with DM.

For this purpose, they conducted a retrospective cohort study of Veterans with DM with statins initiation between 2003 and 2015. The cohort consisted of thiazide users who concomitantly used thiazides and statins for ≥6 months and active comparators (who concomitantly used calcium channel blockers [CCB] but not thiazides and statins for ≥6 months). Those who were less than 18 years old, with CKD (chronic kidney disease) stage 4 or worse, or who used loop diuretics were excluded.

The team propensity-score-matched comparison groups on 99 baseline characteristics including healthcare utilization, demographics, cardiovascular and co-morbidity scores, co-morbidities, laboratory data, vital signs, and medication class usage.

Outcomes

• DM progression (increase in the number of glucose-lowering medication classes, new insulin initiation, and hyperglycemic episodes)
• Kidney disease progression (incidence of diabetic nephropathy, initiation of renal replacement therapy, incidence of CKD, and doubling of serum creatinine)
• Cardiovascular outcomes (cardiac arrest, stroke, acute myocardial infarction)
• Total mortality

Study Findings

The study revealed the following findings:

• 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 an increased risk of DM progression (65.6% in the CCB group versus 68.1% in the thiazide group; odds ratio [OR]: 1.12), decreased risk of kidney progression (16.9% in CCB group versus 16.5 in thiazide group; OR: 0.97), decreased risk of cardiovascular outcomes (15.7% in CCB group versus 14.6% in thiazide group; OR: 0.92), and similar risk of total mortality (19.7% in each group; OR: 1.00).

"Our study attempted to answer a critical clinical question of whether thiazide diuretics should be discontinued or substituted upon statin initiation," the researchers wrote.

"Clinicians should closely monitor diabetes mellitus control when thiazides and statins are used concurrently," they concluded.

Reference

Afify H, Gonzalez-Morales U, Asmar A, Alvarez CA, Mansi IA. Association of Thiazide Diuretics With Diabetes Progression, Kidney Disease Progression, Cardiovascular Outcomes, and Death Among Patients With Diabetes Who Initiate Statins. Am J Cardiol. 2023 Jul 27;203:274-284. doi: 10.1016/j.amjcard.2023.07.057. Epub ahead of print. PMID: 37516035.