Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease: a systematic review and meta-analysis

Shiau, Chu-Hsuan; Tsau, Li-Yun; Kao, Chih-Chin; Peng, Yu-Ching; Bai, Chyi-Huey; Wu, Jeng‑Cheng; Hou, Wen-Hsuan

doi:10.1007/s11255-023-03789-6

Cited by 2 publications

(7 citation statements)

References 80 publications

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“…Renal concentrations of antioxidants, IL-10, and adiponectin increased, whilst the oxidative stress markers, proinflammatory cytokines, leptin, resistin, TGF-β, iNOS, NGAL, and KIM-1 declined with both monotherapies compared to the PC animals. Our findings are aligned with many reports that have underscored the beneficial nephroprotective effects of SGLT2i [15,[20][21][22] and Pcal [24,[27][28][29] that could include glycaemic control with inhibition of renal lipotoxicity, oxidative stress, and inflammation.…”

Section: Discussionsupporting

confidence: 90%

“…Renal SGLT2 and GLUT2 protein expression was also markedly lower in the SGLT2i than the Pcal group. Our results denote more efficient renoprotective actions for SGLT2i against DN, which could be related to its dual glycosuric and natriuretic actions that may provide better controls of blood glucose levels and renal haemodynamics [20][21][22]. Another explanation could be that SGLT2i has stronger modulatory effects than Pcal on renal adipokines and lipogenic pathways.…”

Section: Discussionmentioning

confidence: 66%

“…Others have also shown that SGLT2i increased β-cell mass and insulin production by simultaneously inducing proliferation and inhibiting apoptosis in the pancreas of diabetic animals [47,48]. In clinical settings, SGLT2i also reduced albuminuria, modulated the levels of adipokines, and slowed the progression of chronic kidney disease [15,[20][21][22]. On the other hand, the synthetic analogue of active VD 3 , Pcal, also exerted antidiabetic actions by increasing insulin production following impedance of oxidative stress and inflammation of pancreatic β-cells in rats injected with STZ [49].…”

Section: Discussionmentioning

confidence: 96%

“…Many studies have reported renoprotective effects for the new anti-diabetic drugs, SGLT2i, that counteract hyperglycaemia by simultaneously promoting glucosuria and natriuresis [20][21][22]. In detail, treating diabetic mice with SGLT2i attenuated hyperglycaemia, dyslipidaemia, renal lipotoxicity, glomerular damage, and albuminuria, as well as increased renal PPARα and PPARγ with concurrent decreases in several inflammatory and oxidative stress markers [41][42][43][44].…”

Section: Discussionmentioning

confidence: 99%

“…The inhibitors of SGLT2 (SGLT2i) are novel antidiabetic agents that reduce blood glucose levels by simultaneously promoting glucosuria and natriuresis [19]. More recently, numerous experimental and clinical studies have reported that different analogues of SGLT2i delayed the onset and progression of DN, mainly by reducing oxidative stress and inflammation, whilst improving glomerular filtration [20][21][22][23]. Similarly, the synthetic analogue of active vitamin D (VD3), paricalcitol (Pcal; 19-nor-1α-25-2(OH) D2), is mainly used to treat hyperparathyroidism associated with chronic kidney disease.…”

Section: Of 17mentioning

confidence: 99%

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Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus

Mujalli,

Farrash,

Obaid

et al. 2023

IJMS

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Herein, we measured the antidiabetic and nephroprotective effects of the sodium–glucose cotransporter-2 inhibitor (empagliflozin; SGLT2i) and synthetic active vitamin D (paricalcitol; Pcal) mono- and co-therapy against diabetic nephropathy (DN). Fifty mice were assigned into negative (NC) and positive (PC) control, SGLT2i, Pcal, and SGLT2i+Pcal groups. Following establishment of DN, SGLT2i (5.1 mg/kg/day) and/or Pcal (0.5 µg/kg/day) were used in the designated groups (5 times/week/day). DN was affirmed in the PC group by hyperglycaemia, dyslipidaemia, polyuria, proteinuria, elevated urine protein/creatinine ratio, and abnormal renal biochemical parameters. Renal SREBP-1 lipogenic molecule, adipokines (leptin/resistin), pro-oxidant (MDA/H2O2), pro-inflammatory (IL1β/IL6/TNF-α), tissue damage (iNOS/TGF-β1/NGAL/KIM-1), and apoptosis (TUNEL/Caspase-3) markers also increased in the PC group. In contrast, renal lipolytic (PPARα/PPARγ), adiponectin, antioxidant (GSH/GPx1/SOD1/CAT), and anti-inflammatory (IL10) molecules decreased in the PC group. Both monotherapies increased insulin levels and mitigated hyperglycaemia, dyslipidaemia, renal and urine biochemical profiles alongside renal lipid regulatory molecules, inflammation, and oxidative stress. While SGLT2i monotherapy showed superior effects to Pcal, their combination demonstrated enhanced remedial actions related to metabolic control alongside renal oxidative stress, inflammation, and apoptosis. In conclusion, SGLT2i was better than Pcal monotherapy against DN, and their combination revealed better nephroprotection, plausibly by enhanced glycaemic control with boosted renal antioxidative and anti-inflammatory mechanisms.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Of 17mentioning

confidence: 99%

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Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus

Mujalli,

Farrash,

Obaid

et al. 2023

IJMS

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Effects of Sodium–Glucose Cotransporter 2 Inhibitors in Diabetic and Non-Diabetic Patients with Advanced Chronic Kidney Disease in Peritoneal Dialysis on Residual Kidney Function: In Real-World Data

Moral Berrio,

De La Flor,

Arambarri Segura

et al. 2024

Medicina

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Background and Objectives: Peritoneal dialysis (PD) is a renal replacement therapy modality in which the dialysis dose can be individually adapted according to the patients’ residual kidney function (RKF). RKF is a crucial factor for technique and patient survival. Pharmacological strategies aimed at slowing the loss of RKF in patients on PD are limited. Therefore, we aimed to assess the potential effects and safety of sodium–glucose cotransporter 2 (SGLT-2) inhibitors on the preservation of RKF in patients with and without type 2 diabetes mellitus (T2DM) on PD during an average follow-up of 6 months. Materials and Methods: In this retrospective observational, single-center study on real-world data, we included patients from the Peritoneal Dialysis Unit of the Hospital General Universitario de Ciudad Real, who started treatment with SGLT-2 inhibitors during the period from December 2022 to December 2023. Data on analytical and clinical parameters, RKF, and peritoneal membrane transport function were retrospectively collected at months 0, 3, and 6. Results: Out of 31 patients in our unit, 16 prevalent patients initiated treatment with SGLT-2 inhibitors (13 empagliflozin and 3 dapagliflozin). A total of 62.5% were male and the mean age was 67.3 years. The baseline peritoneal ultrafiltration was higher in the non-diabetic patient (NDMP) group than in the diabetic patient (DMP) group. However, the residual diuresis volume, 24 h residual renal clearance rate of urea in urine, and 24 h proteinuria were higher in the DMP group than in the NDMP group. At the sixth month, patients in both groups preserved RKF and diuresis, with a trend towards a non-significant reduction in proteinuria and blood pressure. Only two patients of the DMP group presented adverse effects. Conclusions: The use of SGLT-2 inhibitors in our sample of patients with and without T2DM on PD appears to be safe and effective to preserve RKF.

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Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients with chronic kidney disease: a systematic review and meta-analysis

Cited by 2 publications

References 80 publications

Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus

Improved Glycaemic Control and Nephroprotective Effects of Empagliflozin and Paricalcitol Co-Therapy in Mice with Type 2 Diabetes Mellitus

Effects of Sodium–Glucose Cotransporter 2 Inhibitors in Diabetic and Non-Diabetic Patients with Advanced Chronic Kidney Disease in Peritoneal Dialysis on Residual Kidney Function: In Real-World Data

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