Kidney Week

Abstract: SA-PO0414

Comparative Effectiveness of GLP-1 Receptor Agonists vs. Mineralocorticoid Receptor Antagonists as Fourth-line Therapy in Patients with Resistant Hypertension and Overweight or Obesity

Session Information

• CKM: Clinical - Epidemiology and Outcomes
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Cardiovascular-Kidney-Metabolic Health

• 602 Cardiovascular-Kidney-Metabolic Health: Clinical

Authors

• Tian, Zhejia, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Zhejia Tian

• Willerding, Jonas Michael, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Jonas Michael Willerding

• Schmidt-Ott, Kai M., Medizinische Hochschule Hannover, Hanover, NDS, Germany

Kai M. Schmidt-Ott, MD, FASN

• Melk, Anette, Medizinische Hochschule Hannover, Hanover, NDS, Germany

Anette Melk, MD, PhD

• Schmidt, Bernhard M.W., Medizinische Hochschule Hannover, Hanover, NDS, Germany

Bernhard M.W. Schmidt, MD, MS

Background

Resistant hypertension (RH) accelerates hypertension-mediated organ damage and is associated with increased cardiovascular risk and mortality. RH is more prevalent among overweight and obese individuals. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been shown to reduce cardiovascular and renal outcomes and lower blood pressure, indicating that GLP-1RAs may represent a promising therapeutic option in this population. This study compares the effectiveness of GLP-1RAs (semaglutide and tirzepatide) and MRAs (spironolactone and eplerenone) as fourth-line therapy on cardiovascular outcomes in patients with RH over 2-year follow-up.

Methods

This multicenter retrospective cohort study included overweight or obese adults with RH identified from the TriNetX database who initiated treatment for RH between June 1, 2017, and March 31, 2025. The primary outcome was the incidence of major adverse cardiovascular events (MACE). Secondary outcomes included mortality, cardiovascular events and renal outcomes. Propensity score matching was employed to construct comparable cohorts of GLP-1RA and MRA users for Kaplan-Meier analysis and Cox proportional hazard model. Blood pressure changes were also evaluated.

Results

Of the 679,866 eligible patients, 22,694 were treated with GLP-1RAs and 5673 with MRAs. After propensity score matching, 4153 GLP-1RA users and matched MRA users were included in the analysis. During a median follow-up of 1.4 years, GLP-1RA therapy was associated with a significantly reduced risk 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. Furthermore, GLP-1RAs exhibited a substantial antihypertensive effect, achieving a systolic blood pressure reduction of -5.7mmHg (95% CI -7.4 to -4.0) at week 12 compared to -6.3mmHg (95%CI -8.0 to -4.7) with MRAs.

Conclusion

GLP-1RA therapy significantly reduced cardiovascular and renal events compared with MRAs, underscoring the importance of treating obesity in patients with resistant hypertension by incorporating GLP-1 RAs into the standard regimen for obese patients with resistant hypertension.