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Renal and cardiovascular effects of SGLT2 inhibitors among hypertensive patients with chronic kidney disease: A systematic review and meta-analysis.


ABSTRACT:

Background

Chronic kidney disease (CKD) is frequently complicated by hypertension, a dual contributor to disease progression and cardiovascular risk. Despite standard therapy with renin-angiotensin-aldosterone system inhibitors, residual risk remains high. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a novel therapy with proven renal and cardiovascular benefits, but their effects in hypertensive CKD patients remain less well defined.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated SGLT2 inhibitors in CKD patients with baseline systolic blood pressure ≥140 mmHg or renovascular disease. PubMed, Embase, and Cochrane Library were searched from inception to August 2024. Eligible RCTs compared an SGLT2 inhibitor versus placebo and reported outcomes in hypertensive subgroups. Primary outcome was a composite of kidney failure, sustained decline in estimated glomerular filtration rate (eGFR ≥40-50 %), or cardiovascular death. Secondary outcomes included kidney-specific endpoints, cardiovascular composite outcomes, and serious adverse events (SAEs). Pooled odds ratios (ORs) were calculated using random-effects models.

Results

Three RCTs were included: CREDENCE (canagliflozin), DAPA-CKD (dapagliflozin), and EMPA-KIDNEY (empagliflozin), encompassing 5436 hypertensive participants. For the primary outcome, SGLT2 inhibitors reduced risk compared with placebo (OR 0.76, 95 % CI 0.65-0.88). Kidney outcomes showed consistent benefit (OR 0.70, 95 % CI 0.58-0.85). Cardiovascular events were modestly reduced (OR 0.79, 95 % CI 0.64-0.97). SAEs were slightly lower with SGLT2 inhibitors (OR 0.85, 95 % CI 0.74-0.96). Overall certainty of evidence was graded as moderate.

Conclusions

Among hypertensive patients with CKD, SGLT2 inhibitors significantly reduce renal disease progression and cardiovascular events while maintaining favorable safety. These findings support their integration into standard therapy for this high-risk population.

SUBMITTER: Javier RM 

PROVIDER: S-EPMC12907684 | biostudies-literature | 2026 Jun

REPOSITORIES: biostudies-literature

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Renal and cardiovascular effects of SGLT2 inhibitors among hypertensive patients with chronic kidney disease: A systematic review and meta-analysis.

Javier R Mohamad RM   Faizin Iqbal I   Andiani   Samudra Dian D   Puspitasari Renny Anggraeni RA   Dharma Ahmad Surya AS   Nurpradika Brianka Yudha BY   Amalia Fauqi F   Danny Siska Suridanda SS   Kuncoro Brm Ario Suryo BAS   Pintaningrum Yusra Y   Firasghani Muhammad Almy MA   Fiohana Puput P   Kosen Yosua Darmadi YD   Kurniawan Kristian K  

International journal of cardiology. Cardiovascular risk and prevention 20260129


<h4>Background</h4>Chronic kidney disease (CKD) is frequently complicated by hypertension, a dual contributor to disease progression and cardiovascular risk. Despite standard therapy with renin-angiotensin-aldosterone system inhibitors, residual risk remains high. Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as a novel therapy with proven renal and cardiovascular benefits, but their effects in hypertensive CKD patients remain less well defined.<h4>Methods</h4>We conducted a sys  ...[more]

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