scholarly journals The dapagliflozin and prevention of adverse outcomes in chronic kidney disease: results of the DAPA-CKD study

2021 ◽  
Vol 93 (6) ◽  
pp. 713-723
Author(s):  
Mikhail M. Batyushin
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Controlled Trial ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Double Blind ◽  
Stage Renal Disease ◽  
End Stage

Aim. The article presents the main results of a randomized, double-blind, parallel, placebo controlled trial of DAPA-CKD. Materials and methods. The study included patients with chronic kidney disease (CKD) and the possibility of using dapagliflozin at a dose of 10 mg once a day compared with placebo. The study involved 386 centers from 21 countries. A total of 4304 patients were included in the study, the average age was 61.8 years, men predominated, 2906 (67.5%) patients had an initial diagnosis of type 2 diabetes. Patients with diabetic and non-diabetic CKD were included with an estimated glomerular filtration rate (eGFR) of 25 to 75 ml/min/1.73 m2 and a urinary albumin/creatinine ratio of 200 to 5000 mg/g. Results. The primary composite endpoint (time to eGFR reduction of 50% or more compared to baseline, time to end-stage renal disease defined as eGFR15 ml/min/1.73 m2, need for chronic dialysis or kidney transplantation, time to renal or cardiovascular death) was shown to occur in 9.2% of patients treated with dapagliflozin and in 14.5% of patients treated with placebo. Also, dapagliflozin therapy was less likely to have a secondary endpoint, such as a combination of a decrease in eGFR by 50% or more, end-stage kidney disease, or renal death. Less frequently, the dapagliflozin group experienced cardiovascular death or hospitalization for heart failure, as well as death from any cause. Conclusion. Thus, dapagliflozin demonstrated the ability, in comparison with placebo, to reduce the primary composite point and a number of secondary composite points in patients with both diabetic and non-diabetic CKD.

scholarly journals Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease

2021 ◽  
pp. ASN.2021020167
Author(s):  
Glenn Chertow ◽  
Priya Vart ◽  
Niels Jongs ◽  
Robert Toto ◽  
Jose Luis Gorriz ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Adverse Events ◽  
Controlled Trial ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Adverse Outcomes ◽  
Serious Adverse Events ◽  
Stage 4 ◽  
Cardiovascular Endpoint

Background In the Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in CKD patients with or without type 2 diabetes. Methods In this prespecified analysis of dapagliflozin's effects in patients with stage 4 CKD (eGFR<30 mL/min per 1.73m2) at baseline, we randomized adults with eGFR of 25-75 mL/min per 1.73m2 and urinary albumin-to-creatinine ratio of 200-5000 mg/g to receive dapagliflozin 10 mg/day or placebo. The primary outcome was a composite of time to ≥50% sustained decline in eGFR, end-stage kidney disease, or kidney or cardiovascular death. Secondary outcomes were a kidney composite (same as the primary endpoint but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death. Results A total of 293 participants received dapagliflozin and 331 received placebo. Relative to placebo, dapagliflozin was associated with reductions in the primary composite endpoint (hazard ratio [HR], 0.73; 95% confidence interval [95% CI], 0.53 to 1.0), the kidney endpoint (HR, 0.71; 95% CI, 0.49 to 1.02), the cardiovascular endpoint (HR, 0.83; 95% CI, 0.45 to 1.53), and the mortality endpoint (HR, 0.68; 95% CI, 0.39 to 1.21). The eGFR slope declined by 2.15 and 3.38 mL/min per 1.73m2 per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. Conclusions Among patients with stage 4 CKD and albuminuria, dapagliflozin's benefits were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.

scholarly journals Rationale and protocol of the Dapagliflozin And Prevention of Adverse outcomes in Chronic Kidney Disease (DAPA-CKD) randomized controlled trial

2020 ◽  
Vol 35 (2) ◽  
pp. 274-282 ◽  
Author(s):  
Hiddo J L Heerspink ◽  
Bergur V Stefansson ◽  
Glenn M Chertow ◽  
Ricardo Correa-Rotter ◽  
Tom Greene ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiovascular Events ◽  
Controlled Trial ◽  
Sglt2 Inhibitor ◽  
Maximum Tolerated Dose ◽  
Adverse Outcomes ◽  
Double Blind

Abstract Background Recent cardiovascular outcome trials have shown that sodium–glucose co-transporter 2 (SGLT2) inhibitors slow the progression of chronic kidney disease (CKD) in patients with type 2 diabetes at high cardiovascular risk. Whether these benefits extend to CKD patients without type 2 diabetes or cardiovascular disease is unknown. The Dapagliflozin and Prevention of Adverse Outcomes in CKD (DAPA-CKD) trial (NCT03036150) will assess the effect of the SGLT2 inhibitor dapagliflozin on renal and cardiovascular events in a broad range of patients with CKD with and without diabetes. Methods DAPA-CKD is a randomized, double-blind, placebo-controlled, trial in which ∼4300 patients with CKD Stages 2–4 and elevated urinary albumin excretion will be enrolled. The vast majority will be receiving a maximum tolerated dose of a renin–angiotensin system inhibitor at enrolment. Results After a screening assessment, eligible patients with a urinary albumin:creatinine ratio ≥200 mg/g and estimated glomerular filtration rate (eGFR) between 25 and 75 mL/min/1.73 m2 are randomly assigned to placebo or dapagliflozin 10 mg/day. Enrolment is monitored to ensure that at least 30% of patients do not have diabetes and that no more than 10% have an eGFR &gt;60 mL/min/1.73 m2. The primary endpoint is a composite of a sustained decline in eGFR of ≥50%, end-stage renal disease, renal death or cardiovascular death. The trial will conclude when 681 primary renal events have occurred, providing 90% power to detect a 22% relative risk reduction (α level of 0.05). Conclusion DAPA-CKD will determine whether the SGLT2 inhibitor dapagliflozin, added to guideline-recommended therapies, safely reduces the rate of renal and cardiovascular events in patients across multiple CKD stages with and without diabetes.

scholarly journals Efficacy and Safety of Dapagliflozin by Baseline Glycemic Status: A Prespecified Analysis From the DAPA-CKD Trial

2021 ◽  
Author(s):  
Frederik Persson ◽  
Peter Rossing ◽  
Priya Vart ◽  
Glenn M. Chertow ◽  
Fan Fan Hou ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Primary Outcome ◽  
Composite Endpoint ◽  
Cardiovascular Death ◽  
Glycemic Status ◽  
End Stage ◽  
Design And Methods ◽  
Egfr Decline

<b>Objective </b> <p>DAPA-CKD demonstrated risk reduction for kidney and cardiovascular outcomes with dapagliflozin versus placebo in participants with chronic kidney disease (CKD) with and without diabetes. We compared outcomes according to baseline glycemic status. </p> <p><b>Research Design and Methods </b></p> <p>We enrolled participants with CKD, estimated glomerular filtration rate (eGFR) <br> 25–75ml/min/1.73m<sup>2 </sup>and urinary albumin-to-creatinine ratio 200–5000mg/g. The primary composite endpoint was sustained eGFR decline ≥50%, end-stage kidney disease, or kidney or cardiovascular death. </p> <p><b>Results </b></p> <p>Of 4304 participants, 738 had normoglycemia, 660 pre-diabetes, and 2906 type 2 diabetes. The effect of dapagliflozin on the primary outcome was consistent (p-interaction=0.19) in normoglycemia (HR [95%CI] 0.62 [0.39–1.01]), pre-diabetes (HR 0.37 [0.21–0.66]) and type 2 diabetes (HR 0.64 [0.52–0.79]). We found no evidence for effect modification on any outcome. Adverse events were similar, with no major hypoglycemia or ketoacidosis in participants with normoglycemia or pre-diabetes. </p> <p><b>Conclusions</b></p> <p>Dapagliflozin safely reduced kidney and cardiovascular events independent of baseline glycemic status. </p>

scholarly journals Metformin: From Immediate Release to Extended Release Formula, Effectiveness, And Safety in Patients With Chronic Kidney Disease

EMJ Diabetes ◽  
2020 ◽  
pp. 70-78
Author(s):  
Giuseppe Derosa ◽  
Rodolfo Rivera ◽  
Angela D'Angelo ◽  
Pamela Maffioli
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Immediate Release ◽  
The World ◽  
Stage Renal Disease ◽  
End Stage

Type 2 diabetes mellitus is currently the main cause of chronic kidney disease, leading to end-stage renal disease in most countries around the world. Metformin is the most commonly prescribed oral antihyperglycaemic in the world and after approval by the U.S. Food and Drug Administration (FDA) in 1994, it is currently recommended as the first-line pharmacological agent for newly diagnosed Type 2 diabetes mellitus by many professional diabetes associations. In this review, the authors analysed efficacy and safety of metformin in patients with chronic kidney disease.

scholarly journals The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) Study Rationale, Design, and Baseline Characteristics

2017 ◽  
Vol 46 (6) ◽  
pp. 462-472 ◽  
Author(s):  
Meg J. Jardine ◽  
Kenneth W. Mahaffey ◽  
Bruce Neal ◽  
Rajiv Agarwal ◽  
George L. Bakris ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Kidney Disease ◽  
Clinical Evaluation ◽  
Cardiovascular Events ◽  
Controlled Trial ◽  
Cardiovascular Death ◽  
Cardiovascular Outcomes ◽  
Double Blind ◽  
Urinary Glucose

Background: People with diabetes and kidney disease have a high risk of cardiovascular events and progression of kidney disease. Sodium glucose co-transporter 2 inhibitors lower plasma glucose by reducing the uptake of filtered glucose in the kidney tubule, leading to increased urinary glucose excretion. They have been repeatedly shown to induce modest natriuresis and reduce HbA1c, blood pressure, weight, and albuminuria in patients with type 2 diabetes. However, the effects of these agents on kidney and cardiovascular events have not been extensively studied in patients with type 2 diabetes and established kidney disease. Methods: The Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) trial aims to compare the efficacy and safety of canagliflozin ­versus placebo at preventing clinically important kidney and cardiovascular outcomes in patients with diabetes and established kidney disease. CREDENCE is a randomized, double-blind, event-driven, placebo-controlled trial set in in 34 countries with a projected duration of ∼5.5 years and enrolling 4,401 adults with type 2 diabetes, estimated glomerular filtration rate ≥30 to <90 mL/min/1.73 m2, and albuminuria (urinary albumin:creatinine ratio >300 to ≤5,000 mg/g). The study has 90% power to detect a 20% reduction in the risk of the primary outcome (α = 0.05), the composite of end-stage kidney disease, doubling of serum creatinine, and renal or cardiovascular death. Conclusion: CREDENCE will provide definitive evidence about the effects of canagliflozin on renal (and cardiovascular) outcomes in patients with type 2 diabetes and established kidney disease. Trial Registration: EudraCT number: 2013-004494-28; ClinicalTrials.gov identifier: NCT02065791.

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