Thiazide Diuretics Are Associated with a Higher Triglyceride-Glucose Index Than Calcium Channel Blockers in Hypertensive Patients

Background: Hypertension is frequently accompanied by metabolic abnormalities that increase cardiovascular risk. The triglyceride–glucose (TyG) index is a practical surrogate marker of insulin resistance. This study aimed to compare TyG index values and related metabolic parameters between patients receiving RAAS blockers plus thiazide/thiazide-like diuretics and those receiving RAAS blockers plus calcium channel blockers (CCBs) as antihypertensive regimens. Methods: In this retrospective observational study, 157 of 189 screened patients met eligibility criteria and were included (RAAS blocker plus thiazide/thiazide-like diuretic, n=95; RAAS blocker plus CCB, n=62). Multivariable linear regression models and inverse probability of treatment weighting (IPTW) analyses were performed to assess the independence of findings from clinical confounders. Results: The TyG index was significantly higher in the diuretic group than in the CCB group [9.21 (9.01– 9.73) vs 8.95 (8.66– 9.40); p< 0.001], as were triglyceride [186.00 vs 142.35 mg/dL; p< 0.001] and uric acid levels [5.70 vs 5.00 mg/dL; p=0.004]. Blood pressure control rates were similar. The treatment group effect remained significant across all adjusted models, including IPTW-weighted regression (β=0.385, p=0.0003). A significant treatment group × diabetes mellitus interaction was observed (p=0.042), suggesting a stronger association in diabetic patients. A dose-stratified analysis within the diuretic group showed a significant dose-response relationship: higher hydrochlorothiazide (25 vs 12.5 mg/day) and indapamide (2.5 vs 1.25 mg/day) doses were both associated with significantly higher TyG index, fasting glucose, and uric acid levels. In an exploratory diuretic subgroup analysis, urea and BUN levels were higher with hydrochlorothiazide than indapamide; however, this analysis was underpowered (indapamide n=24) and should be interpreted with caution. Conclusions: RAAS blocker plus thiazide/thiazide-like diuretic regimens were associated with a significantly higher TyG index and a less favorable metabolic profile than RAAS blocker plus CCB regimens, independent of multiple clinical confounders. Metabolic risk profiles should be considered when selecting antihypertensive combination therapy; prospective studies are needed to establish causality. Keywords: hypertension, triglyceride–glucose index, insulin resistance, thiazide diuretics, calcium channel blockers