SGLT2 inhibitors and finerenone in non-diabetic CKD: a step into the (near) future?
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SUBMITTER: Theodorakopoulou MP
PROVIDER: S-EPMC10768750 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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SGLT2 inhibitors and finerenone in non-diabetic CKD: a step into the (near) future?
Theodorakopoulou Marieta P MP Sarafidis Pantelis P
Clinical kidney journal 20231023 1
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Project description:Results from recent randomized controlled trials on inhibitors of the sodium-glucose cotransporter 2 (SGLT2) have determined a paradigm shift in the treatment of patients with type 2 diabetes mellitus. These agents have been shown not only to ameliorate metabolic control, but also to independently protect from cardiovascular events and to reduce the progression of chronic kidney disease (CKD) in these patients. The magnitude of the nephroprotective effect observed in these studies is likely to make SGLT2 inhibitors the most impactful drug class for the treatment of diabetic patients with CKD since the discovery of renin-angiotensin system inhibitors. Even more surprisingly, SGLT2 inhibitors have also been shown to slow CKD progression in non-diabetic individuals with varying degrees of proteinuria, suggesting that activation of SGLT2 is involved in the pathogenesis of CKD independent of its etiology. As indications continue to expand, it is still unclear whether the observed benefits of SGLT2 inhibitors may extend to CKD patients at lower risk of progression and if their association with other agents may confer additional protection.
| S-EPMC9953060 | biostudies-literature
Project description:BackgroundDapagliflozin and finerenone reduce albuminuria and slow CKD progression, but additive effects remain unstudied. We compared their individual and combined efficacy and safety in patients with non-diabetic CKD.MethodsIn an open-label, randomized clinical trial, we included patients aged 18-80 on maximal tolerated ACE inhibitor or angiotensin receptor blocker with eGFR 25-45 mL/min/1,73 m2 and albuminuria 150-2000 mg/g. Participants received either finerenone 20 mg/day or dapagliflozin 10 mg/day for four weeks, followed by combination therapy for four weeks. Data were collected at baseline, 4 and 8 weeks.ResultsTwenty patients (10 per group) with a mean mGFR of 34 mL/min/1,73 m2 and a mean urine albumin creatinine ratio (UACR) of 469 mg/g were included. Finerenone alone or in addition to dapagliflozin resulted in -24% (95% CI, -36% to -11%) and -34% (95% CI, -47% to -18%) change in UACR, respectively. Dapagliflozin alone or in addition to finerenone resulted in -8% (95% CI, -22 to 9%) and -10% (95% CI, -28% to 12%) change in UACR, respectively. Overall, UACR change after 8 weeks was -36% (95% CI, -46% to -24%). After 8 weeks, systolic blood pressure and mGFR were reduced by 10 mmHg (95% CI, 6-13 mmHg) and 7 mL/min/1,73 m2 (95% CI, 5-8 mL/min/1,73 m2). Adverse effects were minimal.ConclusionsThe combination of finerenone and dapagliflozin was safe and significantly reduced albuminuria. The effect of combination therapy was at least equal to the calculated, combined effect of each of the drugs, suggesting an additive effect on albuminuria. Larger studies assessing long-term effects and safety are warranted.
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Project description:The goal of this study was to compare Next Generation mRNA (RNA-seq) data obtained from whole kidney tissue from WT and untreated, Ramipril treated, and Ramipril/Empagliflozin treated, and Ramipril/Empagliflozin/Finerenone treated Col4a3-/- mice in the 129/SvJ background.
2023-09-01 | GSE226353 | GEO
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| S-EPMC5198295 | biostudies-literature
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| S-EPMC9751670 | biostudies-literature
Project description:SGLT2 inhibitors have emerged as a key disease-modifying therapy to prevent the progression of chronic kidney disease (CKD). These agents prevent decline in kidney function through reduction in glomerular hypertension mediated through tubuloglomerular feedback independent of their effect on glycemic control. The proliferation of clinical trials on SGLT2 inhibitors has rapidly expanded the approved clinical indications for these agents beyond patients with diabetes mellitus (DM). We review the current indications for SGLT2 inhibitors in patients with and without diabetic kidney disease, including new evidence for use in patients with heart failure with or without reduced ejection fraction, stage 4 CKD, and chronic glomerulonephritis. The EMPA-KIDNEY trial was recently stopped early for efficacy suggesting that SGLT2 inhibitors may soon be indicated for patients with CKD without albuminuria. We review practical considerations for prescription of SGLT2 inhibitors, including the anticipated acute decline in estimated glomerular filtration rate (eGFR) on initiation, initiating the lowest dosage used in clinical trials, volume status considerations, and adverse event mitigation. Combination therapy in patients with DM may be considered with agents, including glucagon-like peptide-1 receptor agonists (GLP-1-RAs), novel mineralocorticoid receptor antagonists, and selective endothelin receptor antagonists to reduce residual albuminuria and cardiovascular risk.
| S-EPMC9263228 | biostudies-literature
Project description:Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) worldwide. Glycemic and blood pressure (BP) control are important but not sufficient to attenuate the incidence and progression of DN. Sodium-glucose cotransporter (SGLT) 2 inhibitors are a new class of glucose-lowering agent suggested to exert renoprotective effects in glucose lowering-dependent and independent fashions. Experimental studies have shown that SGLT2 inhibitors attenuate DN in animal models of both type 1 diabetes (T1D) and type 2 diabetes (T2D), indicating a potential renoprotective effect beyond glucose reduction. Renoprotection by SGLT2 inhibitors has been demonstrated in T2D patients with a high cardiovascular risk in randomized controlled trials (RCTs). These favorable effects of SGLT2 inhibitors are explained by several potential mechanisms, including the attenuation of glomerular hyperfiltration, inflammation and oxidative stress. In this review article, we discuss the renoprotective effects of SGLT2 inhibitors by integrating experimental findings with the available clinical data.
| S-EPMC5454992 | biostudies-literature
Project description:BackgroundRandomized controlled trials have demonstrated the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in people with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). However, real-world data on CKD progression and the development of end-stage kidney disease (ESKD) remains scarce. Our aim was to study renal outcomes of people with diabetic kidney disease (DKD) using SGLT2is in a highly prevalent DKD population.MethodsBetween 2016 and 2019 we recruited T2DM patients in the renal and diabetic clinics in a regional hospital in Singapore. Patients prescribed SGLT2is were compared with those on standard anti-diabetic and renoprotective treatment. The outcome measures were CKD progression [a ≥25% decrease from baseline and worsening of estimated glomerular filtration rate (eGFR) categories according to the Kidney Disease: Improving Global Outcomes guidelines] and ESKD (eGFR <15 mL/min/1.73 m2).ResultsWe analysed a total of 4446 subjects; 1598 were on SGLT2is. There was a significant reduction in CKD progression {hazard ratio [HR] 0.60 [95% confidence interval (CI) 0.49-0.74]} with SGLT2is. The HR for eGFR ≥45 mL/min/1.73 m2 and 15-44 mL/min/1.73 m2 was 0.60 (95% CI 0.47-0.76) and 0.43 (95% CI 0.23-0.66), respectively. There was also a reduction in risk for developing ESKD for the entire cohort [HR 0.33 (95% CI 0.17-0.65)] and eGFR 15-44 mL/min/1.73 m2 [HR 0.24 (95% CI 0.09-0.66)]. Compared with canagliflozin and dapagliflozin, empagliflozin showed a sustained risk reduction of renal outcomes across CKD stages 1-4.ConclusionsThis real-world study demonstrates the benefits of SGLT2is on CKD progression and ESKD. The effect is more pronounced in moderate to advanced CKD patients.
| S-EPMC9217649 | biostudies-literature
Project description:ImportanceSodium-glucose cotransporter 2 (SGLT2) inhibitors are associated with lower anemia risk, based on findings from post hoc analyses of the CREDENCE and DAPA-CKD trials; however, the effectiveness of SGLT2 inhibitors in a more generalizable type 2 diabetes (T2D) and chronic kidney disease (CKD) population, with active comparisons pertinent to current practice, is unknown.ObjectiveTo evaluate and compare anemia incidence between SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) among patients with T2D and CKD stages 1 to 3.Design, setting, and participantsThis retrospective cohort study used target trial emulation of an expanded CREDENCE and DAPA-CKD study framework. The study was conducted among adults with T2D and CKD initiating SGLT2 inhibitors or GLP-1 RAs between January 1, 2016, and December 31, 2021, with follow-up until December 31, 2022. The study was conducted at the Chang Gung Medical Foundation, the largest multi-institutional hospital system in Taiwan.ExposuresInitiation of SGLT2 inhibitors or GLP-1 RAs.Main outcomes and measuresThe primary outcome was a composite of anemia outcomes, including anemia event occurrence (hemoglobin level <12-13 g/dL or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification diagnosis codes) or anemia treatment initiation. Changes in hematological parameters, including hemoglobin level, hematocrit level, and red blood cell count, were evaluated during the follow-up period for as long as 3 years.ResultsThe cohort included a total of 13 799 patients with T2D and CKD, initiating SGLT2 inhibitors (12 331 patients; mean [SD] age, 62.4 [12.3] years; 7548 [61.2%] male) or GLP-1 RAs (1468 patients; mean [SD] age, 61.5 [13.3] years; 900 [61.3%] male). After the median follow-up period of 2.5 years, patients receiving SGLT2 inhibitors had lower incidence of composite anemia outcomes (hazard ratio [HR], 0.81; 95% CI, 0.73-0.90) compared with those receiving GLP-1 RAs. SGLT2 inhibitors were associated with a lower incidence of anemia events (HR, 0.79; 95% CI, 0.71-0.87) but not with a lower rate of anemia treatment initiation (HR, 0.99; 95% CI, 0.83-1.19). Changes in hematological parameters for SGLT2 inhibitors and GLP-1 RAs throughout the 3-year follow-up period supported the primary analyses.Conclusions and relevanceIn this multi-institutional cohort study with target trial emulation, SGLT2 inhibitors were associated with a decreased risk of composite anemia outcomes, especially anemia event occurrences. SGLT2 inhibitors may be considered as an adjunct therapy to reduce anemia incidence in patients with T2D and CKD.
| S-EPMC10912959 | biostudies-literature