Effect of SGLT2 inhibitor on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

Feng, Chaojie; Minxiang, Wu; Zheng-yue, Chen; Yu, Xiaoyan; Nie, Zhenyu; Zhao, Yu; Bao, Bin

doi:10.1007/s11255-019-02112-6

Cited by 11 publications

(7 citation statements)

References 86 publications

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“…Sodium glucose co-transporter2 (SGLT2) inhibitors are unique anti-diabetic drugs, since their mechanism of action involves excretion of excessive blood glucose into urine [4]. In the early period after their introduction, there was considerable concern regarding harmful effects on the kidney, since the estimated glomerular filtration rate (eGFR) is temporally reduced soon after the initiation of SGLT2 inhibitor administration [5]. However, to date, many clinical studies have shown SGLT2 inhibitors to block the progression of diabetic nephropathy in the long-term [6–10].…”

Section: Introductionmentioning

confidence: 99%

Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice

Inoue¹,

Matsunaga

Nakatsu³

et al. 2019

Diabetol Metab Syndr

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Background Recently, clinical studies have shown the protective effects of sodium glucose co-transporter2 (SGLT2) inhibitors against progression of diabetic nephropathy, but the underlying molecular mechanisms remain unclear. Methods Diabetic mice were prepared by injecting nicotinamide and streptozotocin, followed by high-sucrose diet feeding (NA/STZ/Suc mice). The SGLT2 inhibitor canagliflozin was administered as a 0.03% (w/w) mixture in the diet for 4 weeks. Then, various parameters and effects of canagliflozin on diabetic nephropathy were investigated. Results Canagliflozin administration to NA/STZ/Suc mice normalized hyperglycemia as well as elevated renal mRNA of collagen 1a1, 1a2, CTGF, TNFα and MCP-1. Microscopic observation revealed reduced fibrotic deposition in the kidneys of canagliflozin-treated NA/STZ/Suc mice. Interestingly, the protein level of Pin1, reportedly involved in the inflammation and fibrosis affecting several tissues, was markedly increased in the NA/STZ/Suc mouse kidney, but this was normalized with canagliflozin treatment. The cells showing increased Pin1 expression in the kidney were mainly mesangial cells, along with podocytes, based on immunohistochemical analysis. Furthermore, it was revealed that canagliflozin induced AMP-activated kinase (AMPK) activation concentration-dependently in CRL1927 mesangial as well as THP-1 macrophage cell lines. AMPK activation was speculated to suppress mesangial cell proliferation and exert anti-inflammatory effects in hematopoietic cells. Conclusion Therefore, we can reasonably suggest that normalized Pin1 expression and AMPK activation contribute to the molecular mechanisms underlying SGLT2 inhibitor-induced suppression of diabetic nephropathy, possibly at least in part by reducing inflammation and fibrotic change.

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Section: Introductionmentioning

confidence: 99%

Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice

Inoue¹,

Matsunaga

Nakatsu³

et al. 2019

Diabetol Metab Syndr

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“…All four reviews that assessed progression of albuminuria presented high quality of evidence (Table 2). Dorsey‐Treviño et al 17 and Chen et al 46 reported RRs of 0.69 (0.66 to 0.73) and 0.71 (0.66 to 0.76), respectively, and Feng et al 48 showed a reduction in SMD of −0.11 (−0.17 to −0.05) in urine albumin/creatinine ratio. Because of methodological differences, Seidu et al 49 did not produce a meta‐analysis in summarizing the results relating to progression of albuminuria.…”

Section: Resultsmentioning

confidence: 99%

Sodium‐glucose cotransporter‐2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews

Augusto

Cassola

Dualib

et al. 2021

Diabetes Obesity Metabolism

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Aims To summarize the evidence from systematic reviews (SRs) of randomized controlled trials (RCTs) evaluating the efficacy and safety of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors versus placebo or active comparators for type 2 diabetes mellitus. Materials and Methods We searched six databases between 2014 and 2021. We assessed the quality of evidence using Assessment of Multiple Systematic Reviews (AMSTAR 2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) and summarized the main outcome results according to their evidence of benefit (PROSPERO ID: CRD42019132431). Results We included 46 SRs, comprising 175 RCTs and 136 096 participants. The results showed “clear evidence of benefit” in relation to: myocardial infarction (odds ratio [OR]/hazard ratio [HR] 0.85 to 0.91); cardiovascular mortality (OR/HR 0.67 to 0.86); heart failure (OR/HR 0.64 to 0.69); albuminuria progression and composite renal outcome (relative risk [RR]/HR 0.55 to 0.63); glycated haemoglobin (HbA1c) versus placebo (mean difference [MD] −0.49% to −0.77% [5.4 to 8.4 mmol/mol]); and weight versus placebo (MD −1.09 kg to −2.99 kg). “Possible benefit” was observed in relation to major adverse cardiovascular events (OR/HR 0.80 to 0.89), all‐cause mortality and nonalcoholic fatty liver disease. SGLT2 inhibitors showed “clear evidence of no effect or equivalence” in relation to stroke and fractures. “Clear evidence of harm” was observed in relation to genital infections (RR/OR 2.06 to 5.25) and ketoacidosis (HR/OR 1.36 to 2.20). Regarding amputation risk and urinary tract infections, we found “no conclusions possible due to lack of evidence”. Conclusions Our results showed that SGLT2 inhibitors have beneficial effects in relation to renal and cardiovascular outcomes (except for stroke), HbA1c and weight. Further studies are needed to assess urinary infections and amputation risk.

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“…Patients treated with empagliflozin are more likely to experience continuous improvement from micro-albuminuria to normal albuminuria or from macro-albuminuria to micro-albuminuria or normal albuminuria but are less likely to experience continuous deterioration from normal albuminuria to micro-albuminuria or macro-albuminuria [20] . A large number of studies have shown that SGLT2i can reduce the level of albuminuria in patients with type 2 diabetes and reduce the risk of progression or deterioration of albuminuria, especially in patients with massive albuminuria [21][22][23][24][25][26][27] . Empagliflozin and canagliflozin have been shown to reduce UACR in patients with type 2 diabetes mellitus complicated with cardiovascular disease.…”

Section: Discussionmentioning

confidence: 99%

Relationship between dapagliflozin and urinary albumin-to-creatinine ratio in patients with diabetes mellitus and cardiovascular disease: an observational study

Wu,

He,

Xia

et al. 2023

Cardiology Plus

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Background and purpose: The potential impact of dapagliflozin on the urinary albumin-to-creatinine ratio (UACR) in patients with type 2 diabetes and cardiovascular disease remained inconclusive. We aimed to investigate the potential impact of dapagliflozin on the UACR in patients with diabetes mellitus complicated with cardiovascular disease. Methods: This is a single-center prospective observation study. Diabetic patients with cardiovascular disease were recruited at authors’ center (both outpatients and inpatients) during a period from June 2019 to November 2020. The study subjects were grouped into a dapagliflozin group (receiving dapagliflozin for at least 6 consecutive months) and a non-sodium-glucose cotransporter 2 inhibitors (SGLT2i) group (not receiving dapagliflozin or any other SGLT2i). LgUACR change at 6 months from the baseline were compared between the two groups. Results: A total of 57 patients were enrolled during a period from June 2019 to November 2020: 35 in the dapagliflozin group versus 22 in the non-SGLT2i group. LgUACR change from the baseline was −0.07 in the dapagliflozin group, and 0.17 in the non-SGLT2i group (P = 0.021). Dapagliflozin was associated with a decrease in UACR in the univariate regression analysis but not in the analysis of covariance. Conclusions: Dapagliflozin may be associated with a decrease in the UACR in patients with diabetes mellitus and cardiovascular disease. In view of the limited sample size, further investigation is needed to verify these findings.

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Effect of SGLT2 inhibitor on renal function in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials

Cited by 11 publications

References 86 publications

Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice

Possible involvement of normalized Pin1 expression level and AMPK activation in the molecular mechanisms underlying renal protective effects of SGLT2 inhibitors in mice

Sodium‐glucose cotransporter‐2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews

Relationship between dapagliflozin and urinary albumin-to-creatinine ratio in patients with diabetes mellitus and cardiovascular disease: an observational study

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