Telmisartan in modern cardiovascular and metabolic pharmacotherapy: An integrated review of AT1-receptor antagonism, PPAR-γ activation, molecular mechanisms, cardiovascular–renal protection, metabolic regulation, neuroprotective effects, pharmacokinetics, clinical evidence, safety, and advanced drug-delivery approaches

Telmisartan is a widely used angiotensin II type 1 (AT1) receptor antagonist with established antihypertensive efficacy and potential pleiotropic effects involving metabolic regulation, inflammation, oxidative stress, and tissue protection. This review provides an integrated overview of telmisartan’s pharmacological properties, molecular mechanisms, pharmacokinetics, cardiovascular and renal protective effects, metabolic and neuroprotective potential, clinical evidence, safety profile, and emerging drug-delivery strategies. Telmisartan inhibits AT1-receptor-mediated actions of angiotensin II, thereby reducing vasoconstriction, aldosterone-related effects, and blood pressure. Its partial peroxisome proliferator-activated receptor-gamma (PPAR-γ) activity has also attracted research interest because of possible effects on insulin sensitivity, glucose metabolism, inflammation, and lipid regulation. Clinical evidence supports its role in hypertension and cardiovascular risk reduction in selected high-risk patients, while studies investigating renal protection, metabolic benefits, and neuroprotection indicate varying degrees of benefit depending on the population and study design. Its long duration of action supports once-daily administration; however, poor aqueous solubility presents a formulation challenge. Emerging approaches, including nanocrystals, polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carriers, liposomes, and transdermal vesicular systems, have demonstrated promising formulation and preclinical pharmacokinetic results. Nevertheless, improvements observed in experimental studies should not be interpreted as established clinical benefits without appropriate human trials. Safety considerations include hypotension, hyperkalemia, renal-function changes, drug interactions, and fetal toxicity during pregnancy. Overall, telmisartan remains an important therapeutic agent in cardiovascular pharmacotherapy, while its additional metabolic and neuroprotective applications and advanced delivery systems require further clinical validation. Future research should prioritize well-designed clinical studies, long-term safety assessment, formulation stability, reproducible manufacturing, and evidence of meaningful improvements in patient outcomes.