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losartan + HCTZ (Gizaar / Hyzaar / Cozaar plus)

✓ Approved

Merck & Co. · AGTR1 · Small Molecule

What is losartan + HCTZ?

losartan + HCTZ is a small molecule developed by Merck & Co.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesGizaar, Hyzaar, Cozaar plus
CompanyMerck & Co.
Drug ClassSmall Molecule
Molecular TargetAGTR1, SLC12A3
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Merck & Co.

Mechanism of Action

Molecular Targets

losartan + HCTZ acts on 2 molecular targets:

AGTR1angiotensin II receptor type 1 (HAT1R, AT1)
SLC12A3solute carrier family 12 member 3 (NCCT, NCC)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

losartan + HCTZ is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Vascular disordersHypertension✓ Approved

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Comparison of angioplasty, stents and conventional medical therapy for symptomatic intracranial atherosclerosis: a network meta-analysis.

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Medical treatment and endovascular therapy are widely employed in the management of symptomatic intracranial atherosclerotic stenosis, however, the comparative effectiveness of these treatment modalities remains uncertain. We searched major Chinese and English databases to identify randomized controlled trials (RCTs) comparing four different endovascular modalities against other comparable non-endovascular therapies for patients with symptomatic intracranial atherosclerotic stenosis (sICAS). Eligible participants were individuals who had experienced a transient ischemic attack (TIA) or non-disabling stroke within the preceding 12 months. The literature search cutoff date was 11 January 2026. For safety outcomes, the SUCRA ranking was as follows: medical treatment (MT) (SUCRA 90.1%) > drug-coated balloons (DCB) (SUCRA 52.8%) > balloon dilatation angioplasty (BDA) (SUCRA 40.7%) > bare metal stents (BMS) (SUCRA 35.4%) > drug-eluting stents (DES) (SUCRA 31.0%). MT exhibited a superior safety profile compared with BMS, with a statistically significant difference (RR = 0.47; 95% CI: 0.31 to 0.72). For long-term outcomes, exploratory SUCRA probability rankings were as follows: BDA (SUCRA 86.7%) > DES (SUCRA 77.4%) > MT (SUCRA 23.8%) > BMS (SUCRA 12.1%), and between-treatment differences were not statistically significant across all interventions. In terms of short-term safety, BMS treatment strategies were significantly inferior to medical treatment (MT), while no statistically significant differences in safety were observed among the various endovascular treatment modalities. In terms of adverse events during long-term follow-up, between-treatment differences were not statistically significant. Despite relatively high SUCRA values for BDA and DES for long-term outcomes, these rankings should be interpreted cautiously given the lack of statistically significant inter-group differences. Further research is required to verify the performance of each endovascular treatment strategy about restenosis. https://www.crd.york.ac.uk/PROSPERO/, CRD420251146704.

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Adipose tissue has a central role in systemic energy balance and the pathogenesis of obesity and its sequelae1,2. In contrast to white adipose tissue, brown adipose tissue (BAT) uses energy to produce heat3. Detectable BAT in humans is associated with decreased prevalence of cardiometabolic diseases4. However, the complete spectrum of health conditions associated with BAT remains unknown, and high-throughput methods to quantify BAT activity in humans are lacking5,6. Here we leveraged big data and artificial intelligence to systematically define the clinical impact of BAT in a cohort of 101,243 patients from a large cancer centre. Our unbiased analyses revealed that, across all diagnoses, cardiovascular and psychiatric diseases were less prevalent in people with BAT. Using a machine learning approach, we semi-automatically quantified BAT activity in approximately 8,700 patients and demonstrated that higher BAT activity, especially in the axillary depot, is associated with lower odds of cardiometabolic diseases and healthier white fat distribution. People with BAT also exhibited more favourable glycaemic parameters, lipid profiles, inflammatory markers and echocardiographic indices. Analysis of medication usage demonstrated that angiotensin receptor blocker use was positively associated with BAT presence. As proof of concept, we showed that the angiotensin receptor blocker losartan increased brown adipocyte activity and whole-body energy expenditure. Altogether, our studies harnessing artificial intelligence and big data identify new clinical phenotypes linked to BAT and serve as a platform for drug repurposing to activate this tissue in humans.

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Pragmatic clinical trials leveraging real-world data, such as the Diuretic Comparison Project (DCP), present unique challenges in measuring treatment adherence compared to traditional randomized controlled trials. In DCP, medications were managed through routine VA care and monitored via pharmacy claims, requiring tailored methods to assess adherence beyond standard measures like medication possession ratio (MPR). To develop a data-driven approach to define protocol treatment adherence for pragmatic comparative effectiveness trials. Structured EHR pharmacy dispense records guided categorization of treatment changes for two diuretics - chlorthalidone (CTD) and hydrochlorothiazide (HCTZ). We examined fill intervals, total drug supply, filling patterns among others to identify prescribing characteristics informing medication adherence definitions and time censoring for per-protocol analysis. Nonadherence was defined as having a gap (>90-days pause in assigned treatment), switch (receiving the other study medication), or discontinuation (without CTD/HCTZ for >90-days). 5,476 patients met nonadherence criteria - 2,851 (52 %) in CTD and 2,625 (48 %) in HCTZ. Switching occurred earlier in CTD patients, gaps were more common in HCTZ, but discontinuation was similar between groups. Defining adherence requires complex decision-making hybrid framework entailing both clinical and statistical expertise. Pragmatic studies should allow flexibility to generate data-driven, clinically-sensitive measures that appropriately describe trial compliance.

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