Comparative effectiveness of GLP-1 receptor agonists versus mineralocorticoid receptor antagonists as fourth-line pharmacological therapy in patients with resistant hypertension and overweight or obesity: a retrospective multicenter cohort study in the USA
- Design
- Retrospective cohort · 4153 participants · Mixed outcome
- Match to healthy normal-weight adults aged 55–75
- Different population[Auto] Participants had obesity/overweight (age/BMI not reported in abstract).
- Could weight loss explain it?
- Possibly[Auto] Participants had obesity and/or type 2 diabetes and the abstract does not separate direct drug effects from weight loss or glycaemic improvement.
- Study tier
- Study tier 3[Auto] Observational design; confounding by indication and healthy-user effects cannot be excluded (auto-provisional).
- Assessment
- Version 1 · automatic, not yet reviewed by a person · Sep 13, 2026
Study facts come from the paper. Population match, weight-loss explanation and study tier are our judgments, made against the reference group of healthy normal-weight adults aged 55–75.
[Auto, unreviewed; quoted from abstract conclusions] In our retrospective study, among adults with resistant hypertension and overweight or obesity, GLP-1RA was associated with lower cardiovascular and kidney risk compared with MRAs despite smaller blood pressure reductions. GLP-1RAs may represent a potential alternative or complementary therapeutic option in this population. Prospective studies are needed to determine whether GLP-1RAs should be incorporated into treatment strategies for resistant hypertension in patients with overweight or obesity.
01Findings
What the study reported
- Drugs
- Semaglutide, Tirzepatide
- Comparator
- MRAs
- Primary outcome
- Not extracted
- Effect
- Not extracted
- 95% confidence interval
- Not extracted
- Follow-up
- 1.4 years
- Adverse events
- Not extracted
- Limitations
- Auto-classified from abstract only; effect estimates, adverse events and limitations not extracted. Requires manual review.
Who was studied
- Obesity status
- obesity/overweight present (all or most)
- Sample size
- 4153
Study quality details
- Study design
- Retrospective cohort
- Sample size
- 4153
- Randomization
- no
- Blinding
- not stated
- Comparator
- not stated
- Follow up duration
- 1.4 years
- Outcome type
- mixed
- Replication
- not assessed (auto)
- Consistency with other evidence
- not assessed (auto)
- Population applicability
- INDIRECT
- Statistical precision
- CI reported: 95% CI 0
- Risk of bias
- not assessed (auto)
- Funding conflicts
- unclear
- Peer review status
- yes
02Funding
Funding and conflicts
- Funding
- None
- Industry funded
- Unclear
- Manufacturer
- AstraZeneca, Sanofi, Boehringer Ingelheim, Amgen, Roche
- Sponsor role
- not reported in abstract
- Author conflicts
- ZT and JMW declare no competing interests. KMSO reports receiving research funding, honoraria or consultancy fees and travel support from German Research Foundation, Urological Research Foundation Berlin, ERA PerMed, COVID-19-Forschungsnetzwerk Niedersachsen, Acadeny2GmbH, Alexion, Alentis, Alnylam, Apellis, Astellas, AstraZeneca, Bayer, BioPorto Diagnostics, Boehringer Ingelheim, Chiesi, CSL Behring, FAST BioMedical, GSK, Novartis, Quark Pharmaceuticals, REATA, Roche, Sanofi, Sobi, Stadapharm, StreamedUp, Vifor Pharma, not related to this article. AM reports receiving lecture fees and honoraria from Daiichi Sankyo and Meta X, not related to this article. BMWS reports receiving lecture fees and honoraria from ADVITOS, Amgen, AstraZeneca, Bayer Vital, Berlin Chemie-Menarini, Boehringer Ingelheim, CytoSorbents, Daichii Sankyo, Miltenyi, Novartis, Pocard, Vifor, not related to this article.
- Independent replication
- unknown
Funding is shown on every study and never used to score it.
04Source
The source, as retrieved
Abstract
[BACKGROUND] Mineralocorticoid receptor antagonists (MRAs) are the guideline-recommended therapy for resistant hypertension. Resistant hypertension is particularly common in individuals with overweight or obesity. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) induce substantial weight loss and reduce cardiovascular and renal events, with modest reductions in blood pressure. Whether GLP-1RAs provide benefit as an alternative therapeutic strategy in patients with resistant hypertension and overweight or obesity is unknown. We compared the effectiveness of GLP-1RAs and MRAs as fourth-line pharmacologic therapy in this population. [METHODS] In this retrospective multicenter cohort study using the TriNetX US Collaborative Network including 67 healthcare organizations, female and male adults with overweight or obesity and resistant hypertension (uncontrolled blood pressure despite ACE-inhibitors/angiotensin receptor blockers, calcium antagonists and diuretics) initiating a fourth-line pharmacological therapy between 01 June 2017 and 31 March 2025 were identified and included. Patients initiating GLP-1RAs (semaglutide or tirzepatide) were compared with those initiating MRAs (spironolactone or eplerenone). The primary outcome was major adverse cardiovascular events (MACE) during 2-year follow-up. Secondary outcomes included all-cause mortality, cardiovascular events, kidney outcomes, and blood pressure changes. Propensity score matching balanced baseline characteristics. Outcomes were analyzed using Kaplan-Meier estimates and Cox proportional hazards models. [FINDINGS] Among 213,309 eligible patients, 22,694 initiated GLP-1RAs and 5673 initiated MRAs. After propensity score matching, 4153 patients remained in each group. During a median follow-up of 1.4 years, GLP-1RA therapy was associated with lower risks of MACE (HR 0.63, 95% CI 0.52-0.78), all-cause mortality (HR 0.34, 95% CI 0.21-0.55), cardiovascular events (HR 0.74, 95% CI 0.59-0.92), major adverse kidney events (HR 0.64, 95% CI 0.46-0.88), and acute kidney injury (HR 0.62, 95% CI 0.46-0.83) compared with MRAs. Systolic blood pressure reductions at 12 weeks were similar (-5.7 [95% CI -4.0 to -7.4] mmHg versus -6.3 [95% CI -4.7 to -8.0] mmHg). [INTERPRETATION] In our retrospective study, among adults with resistant hypertension and overweight or obesity, GLP-1RA was associated with lower cardiovascular and kidney risk compared with MRAs despite smaller blood pressure reductions. GLP-1RAs may represent a potential alternative or complementary therapeutic option in this population. Prospective studies are needed to determine whether GLP-1RAs should be incorporated into treatment strategies for resistant hypertension in patients with overweight or obesity. [FUNDING] None.