Assessing early tubular protective effects of SGLT2 inhibitor empagliflozin against type 2 diabetes mellitus using functional magnetic resonance imaging.

Publisher: Springer Verlag Country of Publication: Germany NLM ID: 9200299 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-5233 (Electronic) Linking ISSN: 09405429 NLM ISO Abbreviation: Acta Diabetol Subsets: MEDLINE

Publication: Berlin : Springer Verlag
Original Publication: Berlin : Springer International, c1991-

Diabetes Mellitus, Type 2*/complications ; Diabetes Mellitus, Type 2*/drug therapy ; Sodium-Glucose Transporter 2 Inhibitors*/therapeutic use ; Glucosides*; Humans ; Benzhydryl Compounds/therapeutic use ; Magnetic Resonance Imaging

Aims: To observe the alterations in functional magnetic resonance imaging parameters in normoalbuminuric type 2 diabetic patients undergoing SGLT2 inhibitor empagliflozin treatment and investigate the early tubular protective effects of the inhibitor.
Methods: This study was performed in normoalbuminuric type 2 diabetes mellitus patients (UACR < 30 mg/g, eGFR ≥ 60 ml/min/1.73 m ² ). The patients were divided into the intervention group (empagliflozin) and the control group (27 cases each). The intervention group was treated with 10 mg/day empagliflozin tablets orally, while the control group had adjustments to their basic treatment stage. The patients were treated for 6 weeks.
Results: The baseline clinical data of the two groups were comparable (P˃0.05). The intervention group exhibited better improvements in blood lipid profiles and more significant reductions in blood uric acid levels compared to the control group (P < 0.05). The two groups had No significant difference in blood pressure changes (P˃0.05). Notably, the intervention group demonstrated a greater reduction in UACR and a more substantial decline in eGFR than the control group (P < 0.05). Regarding functional magnetic resonance imaging parameters, the MD value of the renal medulla region in the intervention group increased after treatment, while the MR2* value of the renal medulla region decreased (P < 0.05).
Conclusions: SGLT2 inhibitor empagliflozin can reduce UACR and eGFR levels in early type 2 diabetic patients with normal proteinuria. Moreover, empagliflozin therapy led to an increase in the MD value and a decrease in the MR2* value of the renal medulla, evidencing the early tubular protective effects of this therapy.
(© 2023. Springer-Verlag Italia S.r.l., part of Springer Nature.)

Levin A et al (2013) Kidney disease: improving global outcomes (KDIGO) CKD work group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 3(1):1–150.
McQueen RB et al (2017) Economic burden of comorbid chronic kidney disease and diabetes. J Med Econ 20(6):585–591. (PMID: 10.1080/13696998.2017.128812728128669)
Sun H et al (2022) IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabetes Res Clin Pract 183:109119. (PMID: 10.1016/j.diabres.2021.10911934879977)
Hoogeveen EK (2022) The epidemiology of diabetic kidney disease. Kidney Dial 2(3):433–442. (PMID: 10.3390/kidneydial2030038)
Duan J et al (2019) Prevalence and risk factors of chronic kidney disease and diabetic kidney disease in Chinese rural residents: a cross-sectional survey. Sci Rep 9(1):10408. (PMID: 10.1038/s41598-019-46857-7313206836639314)
Yang C et al (2020) CKD in China: evolving spectrum and public health implications. Am J Kidney Dis 76(2):258–264. (PMID: 10.1053/j.ajkd.2019.05.03231492486)
Gao B et al (2014) Chinese cohort study of chronic kidney disease: design and methods. Chin Med J 127(11):2180–2185. (PMID: 10.3760/cma.j.issn.0366-6999.2013290624902678)
Yu X, Yang X (2015) Peritoneal dialysis in China: meeting the challenge of chronic kidney failure. Am J Kidney Dis 65(1):147–151. (PMID: 10.1053/j.ajkd.2014.08.02325446022)
Bennett WL et al (2011) Comparative effectiveness and safety of medications for type 2 diabetes: an update including new drugs and 2-drug combinations. Ann Intern Med 154(9):602–613. (PMID: 10.7326/0003-4819-154-9-201105030-00336214030543733115)
Gnudi L, Coward RJ, Long DA (2016) Diabetic nephropathy: perspective on novel molecular mechanisms. Trends Endocrinol Metab 27(11):820–830. (PMID: 10.1016/j.tem.2016.07.00227470431)
Tsimihodimos V et al (2017) Antidiabetic drugs and the kidney. Curr Pharm Des 23(41):6310–6320. (PMID: 10.2174/138161282366617030710322228270062)
Yang W et al (2017) Efficacy and safety of dapagliflozin in Asian patients: a pooled analysis. J Diabet 9(8):787–799. (PMID: 10.1111/1753-0407.12484)
Wanner C et al (2016) Empagliflozin and progression of kidney disease in type 2 diabetes. N Engl J Med 375(4):323–334. (PMID: 10.1056/NEJMoa151592027299675)
Wiviott SD et al (2019) Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med 380(4):347–357. (PMID: 10.1056/NEJMoa181238930415602)
Neal B, Perkovic V, Matthews DR (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 377(21):2099. (PMID: 29166232)
Perkovic V et al (2019) Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med 380(24):2295–2306. (PMID: 10.1056/NEJMoa181174430990260)
Hegde NC et al (2023) Dose-dependent renoprotection efficacy of sglt2 inhibitors in type 2 diabetes: systematic review and network meta-analysis. Acta Diabetol 60(10):1311–1331. (PMID: 10.1007/s00592-023-02126-837322184)
Gilbert RE (2017) Proximal tubulopathy: prime mover and key therapeutic target in diabetic kidney disease. Diabetes 66(4):791–800. (PMID: 10.2337/db16-079628325740)
Feng YZ et al (2018) Intravoxel incoherent motion (IVIM) at 3.0 T: evaluation of early renal function changes in type 2 diabetic patients. Abdom Radiol (NY) 43(10):2764–2773. (PMID: 10.1007/s00261-018-1555-729525883)
Feng YZ et al (2020) Non-invasive assessment of early stage diabetic nephropathy by DTI and BOLD MRI. Br J Radiol 93(1105):20190562. (PMID: 10.1259/bjr.20190562316033476948087)
[Clinical guidelines for prevention and treatment of type 2 diabetes mellitus in the elderly in China (2022 edition)]. Zhonghua Nei Ke Za Zhi, 61(1): 12–50.
Górriz JL et al (2015) Nephroprotection by hypoglycemic agents: do we have supporting data? J Clin Med 4(10):1866–1889. (PMID: 10.3390/jcm4101866265127034626660)
Zhang F et al (2022) Expert consensus on personalized initiation of glucose-lowering therapy in adults with newly diagnosed type 2 diabetes without clinical cardiovascular disease or chronic kidney disease. J Evid Based Med 15(2):168–179. (PMID: 10.1111/jebm.1247435715995)
Ma YC et al (2006) Modified glomerular filtration rate estimating equation for Chinese patients with chronic kidney disease. J Am Soc Nephrol 17(10):2937–2944. (PMID: 10.1681/ASN.200604036816988059)
Wei X et al (2022) Alterations of renal function in patients with diabetic kidney disease: a bold and DTI study. Comput Intell Neurosci 2022:6844102. (PMID: 10.1155/2022/6844102362109989546653)
Zhang Z et al (2023) The value of functional magnetic resonance imaging in the evaluation of diabetic kidney disease: a systematic review and meta-analysis. Front Endocrinol (Lausanne) 14:1226830. (PMID: 10.3389/fendo.2023.122683037484949)
Heerspink HJ et al (2017) Canagliflozin slows progression of renal function decline independently of glycemic effects. J Am Soc Nephrol 28(1):368–375. (PMID: 10.1681/ASN.201603027827539604)
Fine LG, Norman JT (2008) Chronic hypoxia as a mechanism of progression of chronic kidney diseases: from hypothesis to novel therapeutics. Kidney Int 74(7):867–872. (PMID: 10.1038/ki.2008.35018633339)
Ndibalema AR et al (2020) Empagliflozin protects against proximal renal tubular cell injury induced by high glucose via regulation of hypoxia-inducible factor 1-alpha. Diabet Metab Syndr Obes 13:1953–1967. (PMID: 10.2147/DMSO.S243170)
Laursen JC et al. (2021) Acute effects of dapagliflozin on renal oxygenation and perfusion in type 1 diabetes with albuminuria: a randomised, double-blind, placebo-controlled crossover trial. eClinicalMedicine 37.

Keywords: Functional magnetic resonance imaging; Lipids; SGLT2 inhibitor; Treatment; Type 2 diabetes

0 (Sodium-Glucose Transporter 2 Inhibitors)
HDC1R2M35U (empagliflozin)
0 (Benzhydryl Compounds)
0 (Glucosides)

Date Created: 20231220 Date Completed: 20240327 Latest Revision: 20240327

20240327

10.1007/s00592-023-02220-x

38117325