Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study

Heerspink, Hiddo J L; Karasik, Avraham; Thuresson, Marcus; Cohen, Cheli Melzer; Chodick, Gabriel; Khunti, Kamlesh; Wilding, John; Rodrı́guez, Luis A. Garcı́a; Soriano, Lucía Cea; Kohsaka, Shun; Nicolucci, Antonio; Lucisano, Giuseppe; Lin, Fang; Wang, Chih‐Yuan; Wittbrodt, Eric; Fenici, Peter; Kosiborod, Mikhail

doi:10.1016/s2213-8587(19)30384-5

Cited by 251 publications

(302 citation statements)

References 22 publications

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“…Prevention of eGFR decline may indeed protect from MACE not only directly but also indirectly by decreasing progressive decline of renal function. Accordingly, the recent results of CVD-REAL 3 study in over 70,000 diabetic patients, i.e., the first realworld data analysis on the effects of SGLT-2 inhibitors on renal outcomes, are of great interest [22]. Investigators demonstrated that initiation of SGLT-2 inhibitors allowed 51% reduction of the composite outcome of a 50% decline in eGFR or ESKD (3.0 vs 6.3 events per 10,000 patient-years).…”

Section: Sglt-2 Inhibition As Anti-mace Therapy In Diabetic Kidney DImentioning

confidence: 99%

Preventing major adverse cardiovascular events by SGLT-2 inhibition in patients with type 2 diabetes: the role of kidney

Giugliano

Nicola

Maiorino

et al. 2020

Cardiovasc Diabetol

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Cardiovascular outcome trials (CVOTs) have demonstrated a significant reduction of major adverse cardiovascular events (MACE) in patients with type 2 diabetes (T2D) treated by SGLT-2 inhibitors. This holds true in the presence of background therapy with statins in most patients. Noteworthy, this SGLT-2 inhibitors effect is unique because, at variance with other components of cardiorenal protection, MACE prevention does not appear to be a class effect. Here, we present meta-analysis of the four key CVOTs indicating a major role of renal function in determining the extent of MACE prevention, with the benefit increasing in more severe kidney disease, that is, a high-risk condition where effectiveness of the traditional approach with statins is reduced.

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Section: Sglt-2 Inhibition As Anti-mace Therapy In Diabetic Kidney DImentioning

confidence: 99%

Preventing major adverse cardiovascular events by SGLT-2 inhibition in patients with type 2 diabetes: the role of kidney

Giugliano

Nicola

Maiorino

et al. 2020

Cardiovasc Diabetol

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“…52%) were in patients with preserved kidney function (eGFR > 90 ml/min/1.73 m 2 ) and ca. 38% of treatment initiation episodes in patients with an eGFR of 60 to < 90 ml/ min/1.73 m 2 , thus making the study relevant to primary care [41]. Overall, CVD-REAL 3 demonstrated significantly less renal events in the SGLT-2i treatment group across the spectrum of assessed renal outcomes (e.g.…”

Section: Primary Care In Diabetes Managementmentioning

confidence: 94%

“…composite of 50% eGFR decline or ESKD (HR 0.49 [95% CI 0.35-0.67]; p < 0.0001), or ESKD alone (HR 0.33 [95% CI 0.16-0.68]; p = 0.0024), with consistent results across pre-specified subgroups, like concomitant use of ACEis or ARBs. HHF (HR 0.60 [95% CI 0.47-0.76]; p < 0.0001) and all-cause mortality (HR 0.55 [95% CI 0.48-0.64]; p < 0.0001) were decreased compared to other glucoselowering drugs [41].…”

Section: Primary Care In Diabetes Managementmentioning

confidence: 97%

“…DECLARE-TIMI 58 investigated the effect of dapagliflozin in a trial population of which 59.5% (10,186 patients) had no established CVD and demonstrated a 16% risk reduction of 3P-MACE (non-significant) in the multiple risk factors population [11]. In terms of primary prevention of kidney disease, results of SGLT-2 inhibitor CVOTs are backed up by the real-world data of CVD-REAL 3 [41]. The study investigated renal and CV outcomes of SGLT-2is in a total of 71,122 treatment initiation episodes from 65,231 individual subjects in 5 different countries (Israel, U.K., Italy, Taiwan, and Japan), compared to other glucose-lowering drugs.…”

Section: Primary Care In Diabetes Managementmentioning

confidence: 99%

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Report from the 5th cardiovascular outcome trial (CVOT) summit

Schnell¹,

Standl²,

Cos³

et al. 2020

Cardiovasc Diabetol

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The 5th Cardiovascular Outcome Trial (CVOT) Summit was held in Munich on October 24th-25th, 2019. As in previous years, this summit served as a reference meeting for in-depth discussions on the topic of recently completed and presented CVOTs. This year, focus was placed on the CVOTs CAROLINA, CREDENCE, DAPA-HF, REWIND, and PIONEER-6. Trial implications for diabetes management and the impact on new treatment algorithms were highlighted for diabetologists, cardiologists, endocrinologists, nephrologists, and general practitioners. Discussions evolved from CVOTs to additional therapy options for heart failure (ARNI), knowledge gained for the treatment and prevention of heart failure and diabetic kidney disease in populations with and without diabetes, particularly using SGLT-2 inhibitors and GLP-1 receptor agonists. Furthermore, the ever increasing impact of CVOTs and substances tested for primary prevention and primary care was discussed. The 6th Cardiovascular Outcome Trial Summit will be held in Munich on October 29th-30th, 2020 (https ://www.cvot.org).

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“…A post-hoc analysis from recent published trial revealed the risk of AKI may be lower under SGLT2 inhibition [7]. In another study of patients with diabetes, initiation of SGLT2 inhibitor therapy has been shown to be associated with a slower rate of kidney function decline and lower risk of major kidney events compared with initiation of other glucose-lowering drugs [8]. Although current evidence supports their safety, additional efforts are needed to elucidate the long-term impact of these compounds on chronic kidney disease, mineral metabolism, and bone health.…”

Section: Introductionmentioning

confidence: 99%

No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro

Baer

Koch

Freitag

et al. 2020

IJMS

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Gliflozins are inhibitors of the renal proximal tubular sodium-glucose co-transporter-2 (SGLT-2), that inhibit reabsorption of urinary glucose and they are able to reduce hyperglycemia in patients with type 2 diabetes. A renoprotective function of gliflozins has been proven in diabetic nephropathy, but harmful side effects on the kidney have also been described. In the current project, primary highly purified human renal proximal tubular epithelial cells (PTCs) have been shown to express functional SGLT-2, and were used as an in vitro model to study possible cellular damage induced by two therapeutically used gliflozins: empagliflozin and dapagliflozin. Cell viability, proliferation, and cytotoxicity assays revealed that neither empagliflozin nor dapagliflozin induce effects in PTCs cultured in a hyperglycemic environment, or in co-medication with ramipril or hydro-chloro-thiazide. Oxidative stress was significantly lowered by dapagliflozin but not by empagliflozin. No effect of either inhibitor could be detected on mRNA and protein expression of the pro-inflammatory cytokine interleukin-6 and the renal injury markers KIM-1 and NGAL. In conclusion, empa- and dapagliflozin in therapeutic concentrations were shown to induce no direct cell injury in cultured primary renal PTCs in hyperglycemic conditions.

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Kidney outcomes associated with use of SGLT2 inhibitors in real-world clinical practice (CVD-REAL 3): a multinational observational cohort study

Cited by 251 publications

References 22 publications

Preventing major adverse cardiovascular events by SGLT-2 inhibition in patients with type 2 diabetes: the role of kidney

Preventing major adverse cardiovascular events by SGLT-2 inhibition in patients with type 2 diabetes: the role of kidney

Report from the 5th cardiovascular outcome trial (CVOT) summit

No Cytotoxic and Inflammatory Effects of Empagliflozin and Dapagliflozin on Primary Renal Proximal Tubular Epithelial Cells under Diabetic Conditions In Vitro

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