In the age of biologics, kinase inhibitors, and personalized oncology, it may seem counterintuitive that a generic antihypertensive agent first approved in 1995 is reemerging as a topic of active translational research. Yet losartan, the prototypical angiotensin II receptor blocker (ARB), continues to gain momentum in diverse investigational domains. Originally designed for selective blockade of the AT₁ receptor within the renin angiotensin aldosterone system (RAAS), losartan has proven to be more than a vasodilator. It has quietly become a pharmacologic platform a molecule capable of modulating fibrosis, inflammation, uric acid handling, and even neural signaling.
Its enduring appeal stems not only from its well-characterized safety profile and affordability, but from its mechanistic versatility. Over the past two decades, losartan has demonstrated consistent benefit in hypertension, diabetic nephropathy, and heart failure, especially in ACE inhibitor intolerant populations. However, recent years have seen a shift from conventional cardiovascular outcomes toward repurposing efforts that leverage its pleiotropic actions.
The 2024 2025 research cycle has brought a particularly eclectic set of findings: a crossover RCT in pediatric CKD revealing losartan’s uricosuric effects; a head-to-head trial showing superiority of losartan chlorthalidone over HCTZ combinations in blood pressure control; a phase 3 oncology trial evaluating losartan’s stromal remodeling role in pancreatic cancer; and emerging studies probing central AT₁ receptor involvement in emotion regulation and cognition. Each study, while distinct in focus, contributes to a growing narrative that losartan may serve purposes far beyond blood pressure control. The therapeutic reexamination of well-characterized, off-patent agents is both scientifically and pragmatically attractive. This article synthesizes key losartan-focused studies from the past year, highlighting both clinical implications and areas requiring further mechanistic and long-term investigation.
Why Revisit Losartan Data Every Year?
For a drug first approved in the 1990s, losartan continues to surprise researchers and clinicians alike. Originally developed as the first angiotensin II receptor blocker (ARB) for hypertension, its pharmacologic profile RAAS inhibition without bradykinin accumulation has made it a staple of cardiology, nephrology, and internal medicine. But what keeps losartan in the research spotlight today is not just its tolerability or affordability. It’s the expanding scope of potential indications, supported by new randomized trials across specialties.
From pediatric nephrology to oncology and even neurocognitive research, the 2024 2025 publication cycle reveals that losartan is far from a legacy drug. Instead, it is being repurposed and refined, not only to manage blood pressure but to influence fibrosis, inflammation, uric acid metabolism, and neural processing.
This review highlights key randomized trials and exploratory studies from the past year, offering a concise update for clinicians and investigators seeking to understand where losartan is headed next and why we should still be paying close attention.
Uricosuric Benefits in Pediatric CKD Crossover RCT
Elevated serum uric acid is a common finding in children with chronic kidney disease (CKD) and has been linked to faster progression and cardiovascular risk. Until recently, treatment options for hyperuricemia in pediatric CKD were limited and largely extrapolated from adult data. In 2025, a crossover randomized controlled trial by Beaudoin et al., published in Pediatric Nephrology, offers compelling new evidence for losartan’s uricosuric potential in this population (PubMed 40571828). The study enrolled 42 children with CKD stages 2 4 and hyperuricemia. Each participant received losartan 0.75 mg/kg or placebo in alternating 4-week blocks, with a washout in between. Compared to placebo, losartan significantly lowered serum uric acid by a mean of 1.6 mg/dL and showed no decline in GFR or adverse hemodynamic effects. Blood pressure remained stable, and the intervention was well tolerated overall.
Mechanistically, losartan is known to inhibit URAT1, a renal urate transporter, in addition to its RAAS effects. This dual action may position losartan as a particularly attractive option in pediatric nephrology, where treatment goals include not only blood pressure control but long-term nephroprotection.
These findings may shift practice by encouraging early, dual-purpose use of losartan in children with CKD and mild hyperuricemia—an approach now supported by pediatric-level evidence.
Losartan + Chlorthalidone vs Losartan + HCTZ BP Superiority Trial
Thiazide diuretics are frequently combined with ARBs for initial hypertension management, but not all thiazides are pharmacologically equal. In a 2025 randomized trial published by Rucker Joerg et al. in Cardiology and Therapy, researchers directly compared losartan chlorthalidone versus the more common losartan hydrochlorothiazide (HCTZ) combination in patients with stage 1 2 hypertension (SpringerLink). Over 12 weeks, 172 patients were randomized to either combination at equivalent diuretic doses. The chlorthalidone arm produced a greater reduction in 24-hour systolic BP, with a mean decrease of 18.7 mmHg versus 13.2 mmHg for the HCTZ group (p < 0.01). Ambulatory BP monitoring confirmed sustained nighttime control with chlorthalidone, a known advantage due to its longer half-life and duration of action.
However, chlorthalidone was also associated with slightly more hypokalemia and metabolic alkalosis, requiring closer electrolyte monitoring. No significant differences in adherence, renal function, or tolerability were observed. These findings revive an ongoing conversation in hypertension management: should losartan chlorthalidone replace losartan HCTZ as the preferred fixed-dose combination? While HCTZ remains more widely prescribed due to familiarity and availability, this trial strengthens the argument for rethinking diuretic pairing, especially in patients needing tighter BP control.
Oncology: Losartan + Modified FOLFIRINOX in Pancreatic Cancer
A surprising spotlight for losartan in 2025 came not from cardiology or nephrology, but oncology. A phase 3 trial published in Cancer explored its use alongside modified FOLFIRINOX chemotherapy in patients with borderline resectable pancreatic cancer—a notoriously aggressive and treatment-resistant disease (Cancer 2025).
The thing is that losartan remodels tumor stroma. In dense, fibrotic tumors like pancreatic adenocarcinoma, stroma restricts blood flow, limiting chemotherapy penetration. By inhibiting angiotensin II mediated TGF-β signaling, losartan reduces interstitial pressure, opening the way for drugs to reach their target more effectively.
In the trial, 286 patients received neoadjuvant mFOLFIRINOX, with half also receiving 50 mg of losartan daily. The results were compelling: R0 resection rates improved (71% vs 58%), and progression-free survival extended by nearly 3 months. Radiologic tumor shrinkage was also greater in the losartan arm.
Crucially, safety wasn’t sacrificed. Despite being layered onto a potent chemotherapy regimen, losartan did not increase toxicity.
Though still investigational, this trial supports a growing view that RAAS modulation may help overcome chemoresistance: not through cytotoxicity, but by changing the tumor’s physical architecture. It’s an elegant pivot: using a long-standing antihypertensive to improve drug delivery in solid tumors.
CNS Exploration Losartan and Acute Cognitive Effects
Losartan’s potential in neuropsychiatric research may seem unexpected, but it isn’t entirely new. The brain expresses angiotensin II receptors, particularly AT₁, which is involved in stress, emotion, and cognitive modulation. Blocking this receptor may influence not just blood pressure, but social behavior and affective regulation.
In 2025, a small placebo-controlled study examined the acute cognitive and emotional effects of a single 50 mg dose of losartan in healthy adults. Functional MRI and behavioral tasks were used to assess responses to social feedback, reward cues, and ambiguous emotional expressions. Participants who received losartan showed reduced amygdala reactivity to social threat and enhanced prefrontal engagement during emotion regulation tasks. Subjectively, they reported less social anxiety and improved emotional clarity, which are subtle, but intriguing effects.
While the study was limited by small sample size and single-dose design, it reinforces growing interest in renin angiotensin modulation in psychiatric and cognitive disorders. Anxiety, PTSD, and even autism spectrum conditions are being explored in early-phase trials.
If further studies replicate these findings, losartan—or other ARBs—could represent a novel neuropharmacologic strategy, leveraging central AT₁ receptor blockade to modulate emotion and cognition without sedating or addictive properties.
Translational Gaps & Next Research Questions
The recent wave of randomized and exploratory trials involving losartan underscores its pharmacodynamic breadth, when a drug initially developed for vascular modulation is now implicated in fields as diverse as pediatric nephrology, oncology, and neurocognitive science. Yet despite these promising developments, a number of critical translational barriers must be addressed before such findings can meaningfully reshape clinical practice.
Perhaps most notably, the durability of benefit across these emerging indications remains uncertain. In pediatric CKD, the uricosuric effects demonstrated by Beaudoin et al. are compelling, but the trial’s short duration precludes any meaningful assessment of renal preservation or cardiovascular protection over time. Similarly, the encouraging results from the pancreatic cancer trial notably improvements in resectability and progression-free survival require confirmation through overall survival data and external validation before integration into standard oncologic pathways.
From a regulatory standpoint, the path to formal indication expansion for an off-patent agent like losartan is inherently challenging. Many of the newer uses being studied, particularly in oncology and psychiatry, are considered off-label and may struggle to secure large-scale funding or industry support. This reality emphasizes the need for public or cooperative trial funding models if repurposing of generics is to succeed in high-impact areas.
There are also unresolved mechanistic questions, particularly in CNS applications. While preclinical and early-phase human data suggest that central AT₁ receptor blockade may alter stress-reactive neural circuitry, the extent of losartan’s blood brain barrier permeability, its receptor selectivity in neural tissue, and the reproducibility of acute psychocognitive effects in clinical populations remain open areas for investigation.
What emerges from this research cycle is a molecule with multisystem potential, operating at the interface of hemodynamics, metabolism, fibrosis, and neuroregulation. Whether losartan evolves beyond its current role depends not only on trial design and translational science, but on the broader willingness of academic and clinical communities to reconsider the therapeutic value of legacy compounds not as relics, but as rediscovered tools in precision pharmacology.
