Abstract Body: Background:
Blood pressure (BP) control is essential to slowing chronic kidney disease (CKD) progression and reducing cardiovascular risk. While sodium-glucose cotransporter 2 inhibitors (SGLT2i), mineralocorticoid receptor antagonists (MRAs), and GLP-1 receptor agonists (GLP-1 RAs) provide cardiorenal benefits, their relative antihypertensive efficacy in CKD remains unclear.
Methods:
We conducted a network meta-analysis of randomized controlled trials and high-quality observational studies (2015–2025) involving adults with CKD (eGFR <90 mL/min/1.73 m2) that reported BP outcomes with SGLT2i, MRAs (including finerenone), or GLP-1 RAs. The primary outcome was mean change in systolic BP (SBP); secondary outcomes included diastolic BP (DBP) change and hypotension incidence. Subgroup analyses compared early (majority with eGFR ≥45) versus advanced CKD (majority with eGFR <45). Random-effects models were used unless heterogeneity (I2) was negligible. Evidence certainty was graded via GRADE. Funnel plots assessed publication bias, for SGLT2i.
Results:
Seventeen studies were included. SGLT2 inhibitors produced the greatest SBP reduction (–4.66 mmHg; 95% CI: –5.22 to –4.11; I2 = 0.4%), followed by MRAs (–4.12 mmHg; 95% CI: –5.81 to –2.43; I2 = 0.8%). GLP-1 RAs had a non-significant SBP reduction (–0.70 mmHg; 95% CI: –2.33 to 0.93; I2 = 0.8%). Diastolic BP reductions followed a similar trend: SGLT2i (–2.39 mmHg; 95% CI: –2.88 to –1.89, I2 = 0.1%), MRAs (–4.3 mmHg; 95% CI: –3.56 to 0.66, I2 = 0.0%). DBP trend could not be performed for GLP-1 RAs. Subgroup analysis confirmed significant SBP reductions with SGLT2i in both early (–3.61 mmHg; 95% CI: –5.19 to –2.02) and advanced CKD (–2.95 mmHg; 95% CI: –4.10 to –1.79). Hypotension was least frequent with SGLT2i (4.4%) versus MRAs (14.6%); GLP-1 RA trials inconsistently reported hypotension. Visual inspection of funnel plots for SGLT2i suggested minimal publication bias.
Conclusions:
SGLT2i provided the most consistent and clinically meaningful BP reductions in CKD, with high-certainty evidence and the lowest hypotension risk. Their effect may reflect broader populations, volume-mediated mechanisms, and longer follow-up. MRAs also reduced BP but had more hypotension, possibly limiting dosing. GLP-1 RAs offered minimal BP benefit, with low certainty and variable reporting. SGLT2i appear preferable for BP control in CKD, though limited direct comparisons call for further study.