Risk of New-Onset Diabetes with Thiazide Diuretics in Hypertensive patients: A Systematic Review and Meta-Analysis

Abstract

Background: thiazide diuretics are often recommended as the initial treatment of choice for hypertension. Due to their effectiveness and cardiovascular benefits. However, concerns regarding metabolic adverse effects, and particularly new-onset diabetes mellitus (NODM), remain and may deny any long-term advantage. This review and meta-analysis compared the risk of NODM and other classified outcomes using thiazide and thiazide-like diuretics versus not using thiazide diuretics.
Methods: Following the PRISMA 2020 guidelines, a systematic search of PubMed, Scopus, and EMBASE from January 2005 to 2025 was conducted for cohort and randomized controlled trials that reported outcomes of NODM. Extracted data included patient population, type of treatment, blood pressure, cardiovascular events, and adverse events. Combined odds ratios (ORs) were estimated using a random effects model.
Results: Five studies were included in this review (four randomized trials and one cohort; >22,000 patients). There was no significant association in NODM with thiazide treatment, compared with patients not treated with thiazide (OR 1.21, 95%CI 0.91-1.59, p=0.19; I²=48%) A subgroup analysis showed mixed results, with one study demonstrating an increase in the incidence of diabetes while other studies showed no increase. Thiazide use did appear to confer an increase in risk of hypokalemia (OR 6.58, 95% CI 5.49-7.89, p<0.00001).
Conclusion: Thiazide diuretics remain safe and effective in the treatment of hypertension. Although we found risk of hypokalemia and a possible risk of NODM, these risks did not translate into increased cardiovascular morbidity or mortality. Glucose and potassium should be monitored in high-risk patients; however, thiazide will remain a foundation in hypertension therapy.