Retrospective analysis of effects of sodium-glucose co-transporter 2 inhibitor in Japanese type 2 diabetes mellitus patients with chronic kidney disease

Kobayashi, Kazuo; Toyoda, Masao; Kimura, Moritsugu; Hatori, Nobuo; Furuki, Takayuki; Sakai, Hiroyuki; Takihata, Masahiro; Umezono, Tomoya; Ito, Shun; Suzuki, Daisuke; Takeda, Hiroshi; Kanamori, Akira; Degawa, Hisakazu; Yamamoto, Hareaki; Machimura, Hideo; Mokubo, Atsuko; Chin, Keiichi; Obana, Mitsuo; Hishiki, Toshimasa; Aoyama, Kouta; Nakajima, Sachiko; Umezawa, Shinichi; Shimura, Hidetoshi; Aoyama, Togo; Sato, Kazuyoshi; Miyakawa, Masaaki

doi:10.1177/1479164118802759

Cited by 14 publications

(19 citation statements)

References 11 publications

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“…Compared to baseline, the proportion of patients with microalbuminuria decreased by 5.9% with SGLT2 inhibition. In another similar study by Kobayashi et al using the Kanagawa Physicians Association registry, 786 T2D participants with CKD treated with SGLT2 inhibition for a median period of 13 months demonstrated a significant decline in median UACR from 47.1 mg/g creatinine to 41.1 mg/g creatinine . Finally, DARWIN‐T2D was a large real‐world retrospective study conducted in 46 Italian outpatient clinics .…”

Section: Kidney Protection In Cvotsmentioning

confidence: 95%

What have we learned about renal protection from the cardiovascular outcome trials and observational analyses with SGLT2 inhibitors?

Sridhar

Rahman

Cherney

2020

Diabetes Obesity Metabolism

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Over the past 5 years, sodium-glucose cotransport 2 (SGLT2) inhibitors have been increasingly regarded as glycaemic agents with cardiovascular (CV) and renal protective effects. The CV benefits of SGLT2 inhibitors have been well established in patients with type 2 diabetes (T2D) and a range of CV comorbidities at baseline. Subsequently, the renal benefits of SGLT2 inhibitors were established in the CREDENCE trial, a dedicated renal outcome trial where canagliflozin reduced the primary composite renal outcome by 30%. In light of these trials, clinical practice guidelines have rapidly evolved, recommending the use of SGLT2 inhibitors as renal and cardioprotective agents in appropriate patient populations. Accordingly, it is important to have an in-depth understanding of the evidence underlying the use of SGLT2 inhibitors in patients with T2D based on published clinical trials and real-world evidence (RWE) studies, as well as information related to potential safety concerns. To accomplish this, we reviewed the evidence for renal protection and safety with SGLT2 inhibitors in the EMPA-REG OUTCOME, CANVAS Program and DECLARE-TIMI 58 CV safety trials, and in the growing body of evidence emerging from real-world studies. This body of work has shown that SGLT2 inhibitors reduce the risk of surrogate renal endpoints such as albuminuria and mitigate the risk of hard renal endpoints including doubling of serum creatinine and end-stage kidney disease in patients with T2D. K E Y W O R D S diabetic nephropathy, SGLT2 inhibitor 1 | INTRODUCTION Sodium-glucose cotransport-2 (SGLT2) inhibitors have been in clinical use for >5 years and were originally developed and prescribed to achieve additional glucose lowering by inducing glycosuria. As part of Food and Drug Administration (FDA) mandated requirements put in place in 2008, as a novel glucose lowering therapy, SGLT2 inhibitors underwent extensive safety evaluation in cardiovascular outcome trials (CVOTs). Accordingly, over the past 5 years, a large body of evidence has emerged from these CVOTs, and from observational realworld evidence (RWE) studies, as discussed and reviewed elsewhere. 1In stark contrast with other anti-hyperglycaemic agents assessed in CVOTs up to that time, SGLT2 inhibitors were shown to have substantial cardiovascular (CV) and renal protective effects across each medication in the class, and across all subgroups analysed to date.These CVOT results have transformed the way that SGLT2 inhibitors are thought about as therapies for patients with type 2 diabetes (T2D). In perhaps, the same way that ACE inhibitors and ARBs were Vikas S. Sridhar and Habib U. Rahman are the co-first authors.

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Section: Kidney Protection In Cvotsmentioning

confidence: 95%

What have we learned about renal protection from the cardiovascular outcome trials and observational analyses with SGLT2 inhibitors?

Sridhar

Rahman

Cherney

2020

Diabetes Obesity Metabolism

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“…In our previous study, we confirmed the beneficial renal effects of SGLT2 inhibitors in Japanese patients with type 2 DM and CKD. 5,6 In a Japanese prospective study, dapagliflozin significantly improved albuminuria levels and the home BP profile in T2DM and diabetic nephropathy patients, and the improved morning home systolic BP was associated with an albuminuria reduction. 7 From these studies, SGLT2Is are thought to be suitable for the treatment of diabetic patients with CKD.…”

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confidence: 99%

The influence of long‐term administration of SGLT2 inhibitors on blood pressure at the office and at home in patients with type 2 diabetes mellitus and chronic kidney disease

Furuki

Kobayashi

Toyoda

et al. 2020

J of Clinical Hypertension

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Sodium-glucose cotransporter 2 inhibitors (SGLT2Is) are novel oral hypoglycemic agents that increase the urinary excretion of glucose by the inhibition of SGLT2 in the renal proximal tubules. The loss of calories in the form of urinary glucose excretion results in the loss of body weight (BW) and in pleiotropic effects, such as a decrease in blood pressure (BP) and improvements in dyslipidemia or liver function. 1 These pleiotropic effects of SGLT2Is are drawing attention for the treatment of diabetes mellitus (DM) patients. Some large-scale trials, such as the EMPA-REG OUTCOME trial, 2 CANVAS/CANVAS-R program, 3 and DECLARE-TIMI58, 4 that investigated the effects of SGLT2Is on cardiovascular outcomes revealed significant improvements in cardiovascular events and even in diabetic nephropathy in

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“…We reported recently the renoprotective effect of SGLT2i in Japanese T2DM patients with CKD [3]. The multiregression analysis applied in that study demonstrated the importance of a decrease in BP as an independent factor for the improvement of ACR.…”

Section: Discussionmentioning

confidence: 99%

“…The results of several large-scale cardiovascular outcome clinical trials on SGLT2i, such as the EMPA-REG OUTCOME trial [1] and CANVAS/CANVAS-R program [2], showed significant improvement in cardiovascular events and even diabetic nephropathy in T2DM patients. Our group also reported previously that SGLT2i reduce the urinary albumin-creatinine ratio (ACR; mg/gCr) in Japanese T2DM patients with chronic kidney disease (CKD) [3]. This mechanism of this effect was not completely understood and presumed to be indirectly related to a decrease in BP.…”

Section: Introductionmentioning

confidence: 98%

Relation between Blood Pressure Management and Renal Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic Patients with Chronic Kidney Disease

Kobayashi

Toyoda

Kaneyama

et al. 2019

Journal of Diabetes Research

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Aim The renoprotective effect of sodium-glucose cotransporter 2 inhibitors is thought to be due, at least in part, to a decrease in blood pressure. The aim of this study was to determine the renal effects of these inhibitors in low blood pressure patients and the dependence of such effect on blood pressure management status. Methods The subjects of this retrospective study were 740 patients with type 2 diabetes mellitus and chronic kidney disease who had been managed at the clinical facilities of the Kanagawa Physicians Association. Data on blood pressure management status and urinary albumin-creatinine ratio were analyzed before and after treatment. Results Changes in the logarithmic value of urinary albumin-creatinine ratio in 327 patients with blood pressure < 130/80 mmHg at the initiation of treatment and in 413 patients with BP above 130/80 mmHg were −0.13 ± 1.05 and −0.24 ± 0.97, respectively. However, there was no significant difference between the two groups by analysis of covariance models after adjustment of the logarithmic value of urinary albumin-creatinine ratio at initiation of treatment. Changes in the logarithmic value of urinary albumin-creatinine ratio in patients with mean blood pressure of <102 mmHg (n = 537) and those with ≥102 mmHg (n = 203) at the time of the survey were −0.25 ± 1.02 and −0.03 ± 0.97, respectively, and the difference was significant in analysis of covariance models even after adjustment for the logarithmic value of urinary albumin-creatinine ratio at initiation of treatment (p < 0.001). Conclusion Our results confirmed that blood pressure management status after treatment with SGLT2 inhibitors influences the extent of change in urinary albumin-creatinine ratio. Stricter blood pressure management is needed to allow the renoprotective effects of sodium-glucose cotransporter 2 inhibitors.

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Retrospective analysis of effects of sodium-glucose co-transporter 2 inhibitor in Japanese type 2 diabetes mellitus patients with chronic kidney disease

Cited by 14 publications

References 11 publications

What have we learned about renal protection from the cardiovascular outcome trials and observational analyses with SGLT2 inhibitors?

What have we learned about renal protection from the cardiovascular outcome trials and observational analyses with SGLT2 inhibitors?

The influence of long‐term administration of SGLT2 inhibitors on blood pressure at the office and at home in patients with type 2 diabetes mellitus and chronic kidney disease

Relation between Blood Pressure Management and Renal Effects of Sodium-Glucose Cotransporter 2 Inhibitors in Diabetic Patients with Chronic Kidney Disease

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