Diuretics in Hypertension Management: Mechanistic Insights and Clinical Implications for Modern Therapeutics

Diuretics remain a cornerstone in the management of hypertension and various fluid overload conditions, including heart failure, nephrotic syndrome, and liver cirrhosis. This review examines their pharmacological mechanisms, therapeutic applications, and evolving clinical positioning across a range of disease. Over the decades, hypertension guidelines have shifted in their preference for diuretics versus newer antihypertensive agents, often driven by concerns about metabolic side effects and evidence from landmark clinical trials. Despite these fluctuations, thiazide diuretics—especially chlorthalidone and indapamide—have consistently demonstrated strong efficacy in reducing cardiovascular morbidity and mortality, provided that optimal dosing is used to minimize adverse metabolic effects such as hypokalemia, dyslipidemia, and impaired glucose tolerance. The utility of diuretics extends to key patient populations, including those with type 2 diabetes mellitus, a history of stroke or transient ischemic attack, salt-sensitive hypertension, and low-renin states. In these contexts, diuretics often play a central role either as monotherapy or as part of rational combination regimens alongside renin-angiotensin system inhibitors or calcium channel blockers. While diuretic resistance, electrolyte disturbances, and individual variability pose therapeutic challenges, these can often be managed through careful patient selection and monitoring. This review reaffirms the integral role of diuretics in modern antihypertensive strategies and advocates for their personalized application based on patient-specific risk profiles and comorbidities.