Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomised trial

Mosenzon, Ofri; Wiviott, Stephen D.; Cahn, Avivit; Rozenberg, Aliza; Yanuv, Ilan; Goodrich, Erica L.; Murphy, Sabina A.; Heerspink, Hiddo J.L.; Zelniker, Thomas A; Dwyer, Jamie P.; Bhatt, Deepak L.; Leiter, Lawrence A.; McGuire, Darren K.; Wilding, John; Kato, Eri; Gause‐Nilsson, Ingrid; Fredriksson, Martin; Johansson, Peter; Langkilde, Anna Maria; Sabatine, Marc S.

doi:10.1016/s2213-8587(19)30180-9

Cited by 548 publications

(558 citation statements)

References 28 publications

Supporting

Mentioning

475

Contrasting

Unclassified

Order By: Relevance

“…In the SGLT‐2i population included in the EMPA‐REG OUTCOME, CANVAS and DECLARE trials, characterized by a low renal risk (mean eGFR, 60‐90 mL/min/1.73 m 2 ; median UACR, ˂30 mg/mmol), the major renal benefits are obtained in T2D diabetic patients with still preserved renal function at baseline. This finding is supported by a recent analysis of renal outcomes in the large subgroup of the DECLARE population with normal or only mildly impaired eGFR, and with normal albuminuria (70% of patients), showing that dapagliflozin reduced by almost 50% the risk of ESKD and eGFR decline in these patients and, thus, suggesting a major role of SGLT‐2i in the early prevention of DKD. On the other hand, the CREDENCE trial demonstrated that, in DKD patients (eGFR, 30 to <90 mL/min/1.73 m 2 and UACR, >33.9 to 565 mg/mmol), the relative risk of the primary renal outcome (ESKD, a doubling of serum creatinine level, or death from renal or cardiovascular causes) is 30% lower in the canagliflozin group than in the placebo group.…”

Section: Cardiorenal Outcomes From Cardiovascular Outcome Trialssupporting

confidence: 54%

Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Giugliano

Ceriello

Nicola

et al. 2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

We are observing a resurgence of major diabetic vascular complications after a period of dramatic decrease during the period 1990 to 2010. The classical division of cardiovascular prevention into primary (with an event) and secondary (without an event) is largely used to describe cardiovascular risk in type 2 diabetes (T2D); however, there is evidence that the cardiovascular risk in diabetes may range from highest in patients who experienced a previous cardiovascular event to mild in patients with the main risk factors at target. Herein, we present details of the 14 cardiovascular outcome trials (CVOTs) published to date, including the total population investigated, and their separation into primary (T2D + multiple risk factors) and secondary prevention (T2D + established cardiovascular disease [CVD]) populations as detailed within the trials. We also summarize evidence for the effects of dipeptidyl peptidase‐4 inhibitors (DPP‐4i), glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) and sodium glucose co‐transporter‐2 inhibitors (SGLT‐2i) versus placebo on the risk of major cardiovascular events (MACE), heart failure (HF) and diabetic kidney disease (DKD). In primary prevention, SGLT‐2i reduce both the risk of hospitalization for HF and progression of DKD; in secondary prevention, SGLT‐2i are effective on the three endpoints, DPP‐4i are neutral, while GLP1‐RA show mixed results.

show abstract

Section: Cardiorenal Outcomes From Cardiovascular Outcome Trialssupporting

confidence: 54%

Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Giugliano

Ceriello

Nicola

et al. 2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

show abstract

“…Canagliflozin significantly reduced the risk of the primary composite efficacy outcome for the composite of ESRD, doubling of serum creatinine or death from renal or CV causes by 30% ( P = .00001) . In the DECLARE–TIMI 58 trial, dapagliflozin was associated with a 24% reduction in the risk of the composite of at least a 40% decrease in eGFR to less than 60 mL/min/1.73 m, ESRD or death from renal or CV causes, with a 47% reduction in the risk of the composite of at least a 40% decrease in eGFR to less than 60 mL/min/1.73 m, ESRD or death from renal causes, with a 46% reduction in the risk of a sustained decrease in eGFR of at least 40% to less than 60 mL/min/1.73 m, and with a 59% reduction in the risk of ESRD or death from renal causes compared with placebo . The renoprotective benefits of dapagliflozin were observed among patients with a relatively high level of renal function at baseline (mean eGFR, 85 mL/min/1.73 m), indicating a potential role for dapagliflozin in the early prevention of CKD in patients with T2D .…”

Section: Renal Outcomes With Sglt‐2 Inhibitorsmentioning

confidence: 99%

“…Dapagliflozin was associated with a significant reduction in the risk of the composite end point of CV death or hospitalization for heart failure (HF) in patients with T2D and established CVD or CV risk, while significant reductions in the risk of the composite end point of CV death, nonfatal myocardial infarction (MI) or nonfatal stroke were observed with empagliflozin in patients with T2D and established CVD, and with canagliflozin in patients with T2D and established CVD or multiple CV risk factors . Empagliflozin, canagliflozin and dapagliflozin were also associated with a reduction in the risk of hospitalization for HF, as well as a reduction in the risk of kidney disease progression . The American Diabetes Association (ADA) 2019 Standards of Medical Care in Diabetes, the ADA and European Association for the Study of Diabetes 2018 consensus report and the American Association of Clinical Endocrinologists/American College of Endocrinology 2019 consensus report have taken into consideration the CV and renal complications of T2D when providing a revised treatment strategy for T2D, recommending SGLT‐2i therapy with proven CV or renal benefit in patients with established CVD or chronic kidney disease (CKD) with or without CVD .…”

Section: Introductionmentioning

confidence: 99%

Effects of sodium‐glucose cotransporter‐2 inhibitors on the cardiovascular and renal complications of type 2 diabetes

Chilton

2019

Diabetes Obesity Metabolism

View full text Add to dashboard Cite

Sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2is) have been shown to mitigate the risks of cardiovascular (CV) and renal complications in patients with type 2 diabetes (T2D) and CV risk factors or CV disease (CVD). In CV outcomes trials (CVOTs) of patients with T2D and established CVD or multiple CV risk factors, empagliflozin and canagliflozin were associated with significant reductions in the risks of major adverse CV events (MACE), hospitalization for heart failure (HF) and kidney disease progression. In the DECLARE–TIMI 58 study, in which the majority of patients did not have established CVD, dapagliflozin was associated with significant reductions in the composite end point of CV death or hospitalization for HF and was noninferior to placebo with regard to MACE; although patients had relatively good renal function, dapagliflozin also showed renal benefits similar to those seen with empagliflozin and canagliflozin. This article reviews the increased risk of CVD and renal disease in patients with T2D and discusses the potential mechanisms of the cardioprotective and renoprotective effects of SGLT‐2i therapy. The observed improvements in CV and renal outcomes with SGLT‐2is in CVOTs suggest a class effect in this patient population and have influenced treatment guidelines for the way add‐on therapy to metformin is initiated in patients with T2D and high CV risk. The overall cardioprotective and renoprotective effects of SGLT‐2is in patients with T2D and high CV risk are most likely attributable to multiple mechanisms, including cardiac, haemodynamic, metabolic, anti‐inflammatory and renal effects.

show abstract

“…In addition, Dr Ofri Mosenzon (Hadassah Hebrew University Hospital, Jerusalem, Israel) presented cardiorenal outcome results from the Dapagliflozin Effect on Cardiovascular Events (DECLARE) trial (N = 17 160) for SGLT‐2 inhibitor dapagliflozin (10 mg) . In comparison to placebo, dapagliflozin conferred (a) greater improvements in urine albumin‐to‐creatinine ratio (UACR) and (b) lower rates of UACR deterioration vs placebo.…”

Section: American Diabetes Association 79th Scientific Session Diabetmentioning

confidence: 99%

Diabetes news

Biba

Teng

Kurian

et al. 2019

Journal of Diabetes

View full text Add to dashboard Cite

Ursula Biba, Rhea W. Teng, Martin J. Kurian, Ann M. Carracher, and Kelly L. Close are of Close Concerns (http://www.closeconcerns.com), a healthcare information company focused exclusively on diabetes and obesity care. Close Concerns publishes Closer Look, a periodical that brings together news and insights in these areas. Each month, the Journal of Diabetes includes this News feature, in which Biba, Teng, Kurian, Carracher, and Close review the latest developments relevant to researchers and clinicians.

show abstract

Effects of dapagliflozin on development and progression of kidney disease in patients with type 2 diabetes: an analysis from the DECLARE–TIMI 58 randomised trial

Cited by 548 publications

References 28 publications

Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Primary versus secondary cardiorenal prevention in type 2 diabetes: Which newer anti‐hyperglycaemic drug matters?

Effects of sodium‐glucose cotransporter‐2 inhibitors on the cardiovascular and renal complications of type 2 diabetes

Diabetes news

Contact Info

Product

Resources

About