Insights from CREDENCE trial indicate an acute drop in estimated glomerular filtration rate during treatment with canagliflozin with implications for clinical practice

Oda, Megumi; Jardine, Meg; Agarwal, Rajiv; Bakris, George L.; Cannon, Christopher P.; Charytan, David M.; Zeeuw, Dick de; Edwards, Robert; Greene, Tom; Levin, Adeera; Lim, Soo Kun; Mahaffey, Kenneth W.; Neal, Bruce; Pollock, Carol; Rosenthal, Norman; Wheeler, David C.; Zhang, Hong; Zinman, Bernard; Perkovic, Vlado; Heerspink, Hiddo J L

doi:10.1016/j.kint.2020.10.042

Cited by 117 publications

(170 citation statements)

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“…These beneficial effects are attributed to decreased sodium resorption in the proximal tubule and normalization of tubuloglomerular feedback, resulting in reduced intraglomerular pressure. Clinically this is manifested by an acute reversible dip in glomerular filtration rate (GFR) 4,5 . However, although effective at a population level, the albuminuric response to SGLT2 inhibitors varies markedly between individual patients, leaving a proportion of patients at high risk of kidney and cardiovascular outcomes 6–9 .…”

Section: Introductionmentioning

confidence: 99%

Renal haemodynamic response to sodium‐glucose cotransporter‐2 inhibition does not depend on protein intake: An analysis of three randomized controlled trials

Beek

Cherney

Laverman

et al. 2021

Diabetes Obesity Metabolism

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High protein intake may increase intraglomerular pressure through dilation of the afferent arteriole. Sodium-glucose cotransporter-2 (SGLT2) inhibitors may reduce intraglomerular pressure through activation of tubuloglomerular feedback. Given these opposing effects, we assessed whether the effect of dapagliflozin on glomerular filtration rate (GFR) and urinary albumin-to-creatinine ratio (UACR) was modified by estimated dietary protein intake using data from three separate randomized controlled trials (DELIGHT, IMPROVE and DIAMOND). The median protein intake was 58.4, 63.6 and 90.0 g/d, respectively. In the DELIGHT trial (n = 233), dapagliflozin compared to placebo caused an acute and reversible dip in GFR of 2.1 and 2.2 mL/min/1.73 m 2 , and reduced UACR by 20.5% and 28.4% in participants with high and low protein intake, respectively. Similarly, in IMPROVE (n = 30) and DIAMOND (n = 53), the effect of dapagliflozin on GFR and UACR was comparable in participants with high and low protein intake (all P for interaction > 0.40). This post hoc, exploratory analysis of three clinical trials suggests that dietary protein intake does not modify the individual response of clinical kidney variables to dapagliflozin.

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Section: Introductionmentioning

confidence: 99%

Renal haemodynamic response to sodium‐glucose cotransporter‐2 inhibition does not depend on protein intake: An analysis of three randomized controlled trials

Beek

Cherney

Laverman

et al. 2021

Diabetes Obesity Metabolism

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“…Findings from previous phase III studies of canagliflozin in patients with T2DM suggested that a reduction in eGFR occurs during the early phase of treatment with canagliflozin (the first 4–6 weeks) ( Bode et al, 2013 ; Cefalu et al, 2013 ; Leiter et al, 2015 ). Moreover, insights from CREDENCE trial indicated that a drop in eGFR of up to 30% was not an indication to stop canagliflozin as it did not map on to an increase risk of adverse events ( Oshima et al, 2021 ). In the present analysis, we have shown that there is a small decrease in eGFR in patients who are treated with 300 mg/ day canagliflozin follow-up durations more than 13 weeks, but there was a great deal of heterogeneity among the included trials.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have also shown that Canaglifozin increases the risk of adverse renal events and acute kidney injury in patients with predisposing factors such as hypoglycemia, chronic kidney disease (CKD), heart failure, and potentially nephrotoxic drugs ( Vasilakou et al, 2013 ; Tang et al, 2017 ). Therefore, concern has been raised in terms of the effect of canagliflozin on renal function ( Oshima et al, 2021 ). Moreover, whether the effects of canagliflozin on renal function are dose-dependent remains uncertain.…”

Section: Introductionmentioning

confidence: 99%

Canagliflozin for Prevention of Cardiovascular and Renal Outcomes in type2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

et al. 2021

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Objective: We aimed to evaluate the efficacy of canagliflozin for the treatment of specific cardiovascular and renal outcomes in Type 2 diabetes mellitus (T2DM) patients by means of a systematic review and meta-analysis.Methods: We performed comprehensive searches of PubMed, the Cochrane Library, and Embase for randomized, placebo-controlled trials of the treatment of T2DM with canagliflozin that were published to 28 September 2020. The cardiovascular outcomes recorded were cardiovascular mortality, heart failure, myocardial infarction, and stroke. The renal composite outcomes recorded were end-stage renal disease (ESRD), renal death. The data for the principal cardiovascular outcomes, ESRD, and renal death were pooled and expressed as Hazard ratios (HRs) with 95% confidence intervals (CIs). Two reviewers independently selected the trials and extracted the data.Results: We identified a total of 1,741 publications, leaving 96 for their titles, abstracts and full-text review. Of these, 10 trials met the inclusion criteria and were finally included in our meta-analysis. The meta-analysis showed that canagliflozin significantly reduced the risk of heart failure in T2DM by 36% (HR 0.64, 95% CI 0.53 to 0.77, p = 0.000). The effects of canagliflozin on non-fatal myocardial infarction or non-fatal stroke (HR 0.84, 95% CI: 0.76 to 0.93, p = 0.001), cardiovascular mortality (HR 0.84, 95% CI 0.72 to 0.97, p = 0.021), and myocardial infarction (HR 0.84, 95% CI 0.70 to 1.00, p = 0.045) in patients with T2DM were relatively small, reducing the risks by 16%. In addition, canagliflozin reduced the risk of stroke in T2DM patients by 13% (HR 0.87, 95% CI 0.71 to 1.06, p = 0.166). Moreover, canagliflozin significantly reduced the risk of the composite renal event of ESRD or renal death by 36% (HR 0.64, 95% CI 0.54 to 0.75, p = 0.000).Conclusion: This meta-analysis suggests that canagliflozin protects against cardiovascular and renal outcomes in patients with T2DM.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], identifier [CRD42020210315]

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“…Der Effekt trat in der Canagliflozingruppe deutlich häufiger auf (die Odds Ratio [OR] für einen Nierenfunktionsverlust von > 10 % [„decline“] lag unter Canagliflozin im Vergleich zu Placebo bei 3,03 [95 %-KI: 2,65–3,47]), stellte sich jedoch nicht bei allen Teilnehmern der Verumgruppe ein („non-decliners“). Die positiven Langzeiteffekte auf die Nierenfunktion waren jedoch auch in der Gruppe der „non-decliners“ feststellbar [ 13 ]. Eine Normalisierung der intraglomerulären Druckverhältnisse allein kann daher wahrscheinlich nicht die positiven Effekte auf die renale Funktion erklären.…”

Section: Introductionunclassified

“…Ein Abfall um mehr als 30 % der initialen eGFR war in der Canagliflozingruppe sogar mit höheren Nebenwirkungsraten assoziiert. Die Autoren empfehlen daher, einen initialen eGFR-Abfall nur bis zu dieser Grenze zu tolerieren [ 13 ].…”

Section: Introductionunclassified

SGLT2-Inhibitoren: Was gibt es Neues?

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Menne

2021

Nephrologe

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Insights from CREDENCE trial indicate an acute drop in estimated glomerular filtration rate during treatment with canagliflozin with implications for clinical practice

Cited by 117 publications

References 20 publications

Renal haemodynamic response to sodium‐glucose cotransporter‐2 inhibition does not depend on protein intake: An analysis of three randomized controlled trials

Renal haemodynamic response to sodium‐glucose cotransporter‐2 inhibition does not depend on protein intake: An analysis of three randomized controlled trials

Canagliflozin for Prevention of Cardiovascular and Renal Outcomes in type2 Diabetes: A Systematic Review and Meta-analysis of Randomized Controlled Trials

SGLT2-Inhibitoren: Was gibt es Neues?

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