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September 3, 2026International Journal of General MedicineOpen Access

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

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Why the study?

Hypertension often features metabolic abnormalities increasing cardiovascular risk, and the comparative effect of different antihypertensive combinations on the triglyceride-glucose index remained unclear.

Does a RAAS blocker plus thiazide/thiazide-like diuretic increase the triglyceride-glucose index compared to a RAAS blocker plus calcium channel blocker in hypertensive patients?

Population

157 hypertensive patients meeting eligibility criteria

Comparison

RAAS blockers plus thiazide/thiazide-like diuretics vs RAAS blockers plus CCBs

Design

Retrospective observational study

Key result

RAAS blocker plus thiazide/thiazide-like diuretic therapy was associated with a significantly higher TyG index compared to RAAS blocker plus CCB therapy (β=0.385) in hypertensive patients.

Authors

SESertaş ErarslanAAAycan AcetOKOsman Nurullah Karagoz

Discussion

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Overview

Thiazide addition to RAAS blockade was associated with higher TyG index; hypothesis-generating for metabolic effects and requires prospective confirmation.

Key Points

  • To compare triglyceride-glucose (TyG) index values and related metabolic parameters between hypertensive patients receiving RAAS blockers combined with either thiazide diuretics or calcium channel blockers.
  • Conducted a retrospective observational study of 157 hypertensive patients prescribed a RAAS blocker plus a thiazide/thiazide-like diuretic (n=95) or a RAAS blocker plus a calcium channel blocker (n=62).
  • Adjusted for clinical confounders using multivariable linear regression and inverse probability of treatment weighting (IPTW), alongside dose-stratified diuretic analyses.
  • 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 levels (186.00 vs 142.35 mg/dL; p < 0.001) and uric acid levels (5.70 vs 5.00 mg/dL; p = 0.004).
  • The treatment effect remained significant in IPTW-weighted regression (β = 0.385, p = 0.0003), with a significant interaction observed for diabetes mellitus (p = 0.042) and a dose-dependent increase in TyG index with higher hydrochlorothiazide and indapamide doses.

Study Design

Type

Observational (n=157)

Multicenter

No

Structured PICO

Does a RAAS blocker plus thiazide/thiazide-like diuretic increase the triglyceride-glucose index compared to a RAAS blocker plus calcium channel blocker in hypertensive patients?

P
Population
157 adults with essential hypertension receiving dual antihypertensive therapy (RAAS blocker plus either a thiazide diuretic or CCB) for at least 6 months.
E
Exposure
RAAS blocker (ACE inhibitor or ARB) plus thiazide/thiazide-like diuretic (hydrochlorothiazide 12.5-25 mg/day or indapamide 1.25-2.5 mg/day) for at least 6 months.
C
Comparator
RAAS blocker (ACE inhibitor or ARB) plus calcium channel blocker (amlodipine 5-10 mg/day) for at least 6 months.
O
Outcome
Triglyceride-glucose (TyG) indexsurrogate

Main Result

Mean Difference: 0.385 (95% CI 0.181–0.589)

Absolute Event Rate: 9.21% vs 8.95%

p-value: p=0.0003

In hypertensive patients, combining a RAAS blocker with a thiazide diuretic is associated with a higher triglyceride-glucose index and worse metabolic profile compared to a CCB combination.

Limitations

  • Retrospective observational design precludes causal inference
  • Absence of pre-treatment metabolic baselines
  • Data on statin/lipid-lowering therapy, antidiabetic medications, diabetes duration, and urinary protein excretion/albuminuria were unavailable
  • Limited number of male participants
  • Single-center setting and relatively small sample size
  • Retrospective nature
  • Exact treatment durations not systematically recorded
  • Data on statin use and antidiabetic medications unavailable
  • Small sample size for indapamide subgroup

Cite This Study

Erarslan et al. (2026) conducted an observational in Essential hypertension (n=157). RAAS blocker plus thiazide/thiazide-like diuretic vs. RAAS blocker plus calcium channel blocker was evaluated on Triglyceride-glucose (TyG) index (β=0.385, 95% CI 0.181-0.589, p=0.0003). RAAS blocker plus thiazide/thiazide-like diuretic therapy was associated with a significantly higher TyG index compared to RAAS blocker plus CCB therapy (β=0.385) in hypertensive patients.

synapsesocial.com/papers/6a993576636c6408cfa7db1dhttps://doi.org/10.2147/ijgm.s640405
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