Recent clinical evidence continues to expand the therapeutic potential of sodium-glucose cotransporter-2 (SGLT2) inhibitors beyond their original development for glycemic control in type 2 diabetes. New research presented at the National Kidney Foundation Spring Clinical Meeting and published in the Journal of Clinical Pharmacy and Therapeutics highlights significant renal benefits in patients with heart failure (HF) and chronic kidney disease (CKD).
Empagliflozin Demonstrates Renoprotection in Heart Failure
A comprehensive meta-analysis investigating the renal benefits of empagliflozin (Jardiance) in heart failure patients has revealed promising results. The study analyzed data from four randomized controlled trials encompassing 10,340 participants, with 5,171 receiving empagliflozin and 5,169 receiving placebo.
The findings showed empagliflozin was associated with a statistically significant 30% reduction in the risk of acute kidney injury (risk ratio [RR] 0.70; 95% CI, 0.56-0.87; P = .002) and a remarkable 63% reduction in renal failure risk (RR 0.37; 95% CI, 0.37-0.86; P = .007). Both results demonstrated no observed interstudy heterogeneity (I²=0%).
While there was a trend toward increased estimated glomerular filtration rate (eGFR) in the empagliflozin group, this effect did not reach statistical significance (standard mean difference [SMD] 5.90; 95% CI, −0.03 to 11.83; P = .05). Similarly, the slightly higher risk of urinary tract infections in the empagliflozin group was not statistically significant (RR 1.35; 95% CI, 0.89-2.04; P = .15).
SGLT2 Inhibitors Improve Anemia Markers in CKD
A separate systematic review and meta-analysis published in the Journal of Clinical Pharmacy and Therapeutics found that SGLT2 inhibitors significantly improved anemia markers in patients with CKD. The analysis included multiple SGLT2 inhibitors: empagliflozin, dapagliflozin (Farxiga), and canagliflozin (Invokana).
The meta-analysis examined five studies focusing on hemoglobin (Hb) levels, comprising 3,326 participants treated with SGLT2 inhibitors and 2,798 controls. Three studies focused on hematocrit (Hct) levels with 1,339 participants receiving SGLT2 inhibitors and 785 controls.
Results demonstrated that SGLT2 inhibitors significantly increased Hb levels (standard difference in means [SE], −0.350; 95% CI, −0.401 to −0.299) and Hct levels (SE, −0.453; 95% CI, −0.829 to 0.077) compared with controls.
The researchers noted that the anemia-correcting benefits can be achieved with relatively low doses, minimizing potential toxicity. Treatment duration and dosage appeared to influence outcomes, with dapagliflozin showing a gradual increase in Hct levels over four months, while canagliflozin at 100 mg daily demonstrated sustained increases in Hb and Hct levels over 26 to 52 weeks.
Addressing the Implementation Gap
Despite robust evidence supporting the cardiorenal benefits of SGLT2 inhibitors, prescribing remains suboptimal, particularly in primary care settings. Diabetic kidney disease accounts for approximately half of all dialysis initiations in the United States, highlighting the urgent need for early and effective treatment strategies.
To address this gap, a collaborative initiative between primary care, nephrology, and pharmacy professionals has developed a novel prescription algorithm and decision tree to guide clinicians in initiating SGLT2 inhibitors. The tool was made widely accessible through a pharmacy website and supported by twice-monthly educational sessions led by a nephrology nurse practitioner and pharmacist.
Mechanisms of Benefit
SGLT2 inhibitors appear to provide renal protection through multiple mechanisms. In CKD, these agents have shown strong benefits in reducing proteinuria and slowing disease progression by lowering intraglomerular pressure and renin activity.
The improvement in anemia markers may be attributed to enhanced tissue oxygen delivery, diuretic effects reducing plasma volume, and stimulation of erythropoietin secretion. These mechanisms align with the established renal and cardiovascular protective effects of SGLT2 inhibitors.
Clinical Implications
The 2024 KDIGO updated guideline reflects the growing evidence supporting SGLT2 inhibitors, with recommendation 3.7.1 strongly supporting their use in patients with type 2 diabetes, CKD, and an estimated glomerular filtration rate (eGFR) of at least 20 ml/min per 1.73 m².
The dual findings of renoprotection in heart failure and anemia improvement in CKD underscore the multifaceted therapeutic value of SGLT2 inhibitors in nephrology care. These agents now demonstrate potential benefits across the spectrum of cardiorenal disease, from slowing CKD progression to reducing cardiovascular risk and addressing common complications like anemia.
Moving forward, combined efforts—clinical validation paired with implementation strategies—are critical to realizing the full potential of SGLT2 inhibitors and improving long-term outcomes for patients with cardiorenal comorbidities. Future studies should prioritize addressing heterogeneity in study protocols and include broader participant comorbidities to enhance understanding of SGLT2 inhibitors' efficacy across different patient populations.
