EUROPEAN ASSOCIATION FOR THE STUDY OF DIABETES OFFICIAL HIGHLIGHTS

EUROPEAN ASSOCIATION FOR THE STUDY OF DIABETES

Conference summaries


T2D & NEPHROPATY

CREDENCE – Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Presented by: Carol Pollock, MBBS, PhD, FRACP, AAHMS
Kolling Institute of Medical Research, Sydney Medical School, University of Sydney, Australia
Hiddo Lambers Heerspink, PharmD, PhD
George Institute for Global Health, University of New South Wales, Sydney, Australia
Kenneth W. Mahaffey, MD
Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, USA
  • CREDENCE investigated the effects of canagliflozin on renal outcomes in patients with type 2 diabetes and albuminuric chronic kidney disease (CKD).
  • In patients with type 2 diabetes and CKD, canagliflozin reduces the risk of cardiac and renal events, even in patients without prior cardiovascular disease.
  • Based on CREDENCE, the American Diabetes Association recently updated its Standards of Care for patients with type 2 diabetes and diabetic kidney disease.

In several trials designed to meet regulatory requirements for cardiovascular safety of sodium-glucose cotransporter 2 (SGLT2) inhibitors, reductions in cardiovascular events were seen. Secondary and exploratory analyses of these trials suggested that SGLT2 inhibition might improve renal outcomes.

  • Assess the effects of the SGLT2 inhibitor canagliflozin on renal outcomes in patients with type 2 diabetes and albuminuric CKD.

Type of study, patients, and inclusion criteria

  • Double-blind, randomised trial.
  • Type 2 diabetes and albuminuric CKD.
  • All patients had an estimated glomerular filtration rate (eGFR) of 30 to <90 mL/min/1.73 m2 and albuminuria (ratio of albumin (mg) to creatinine (g), >300 to 5000) and were treated with renin–angiotensin system blockade.

Patient population

  • Total patients randomised: 4401.
  • Canagliflozin 100 mg/day (n = 2202).
  • Placebo (n = 2199).

Primary outcome measure

  • Composite of end-stage kidney disease (ESKD – dialysis, transplantation, or a sustained eGFR of <15 mL/min/1.73 m2), a doubling of serum creatinine level, or death from renal or cardiovascular causes.
  • The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee, after having randomised 4401 patients with a median follow-up of 2.62 years.
  • The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (HR, 0.70; 95% CI, 0.59-0.82; P = 0.00001).
  • The relative risk of the renal-specific composite of ESKD, a doubling of the creatinine level, or death from renal causes was lower by 34% (HR, 0.66; 95% CI, 0.53-0.81; P <0.001), and the relative risk of ESKD was lower by 32% (HR, 0.68; 95% CI, 0.54-0.86; P = 0.002).
  • The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (HR, 0.80; 95% CI, 0.67-0.95; P = 0.01) and hospitalisation for heart failure (HR, 0.61; 95% CI, 0.47-0.80; P <0.001).
  • Canagliflozin reduced the risk of major cardiovascular events overall (HR, 0.80 (95% CI, 0.67-0.95); P=0.01), with consistent reductions in both the primary (HR, 0.68 (95% CI, 0.49-0.94)) and secondary (HR, 0.85 (95% CI, 0.69-1.06)) prevention groups (P for interaction = 0.25).
  • The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalisation for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome).
  • In patients with type 2 diabetes and CKD, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years.
  • The reduced risk was also seen in participants who did not have previous cardiovascular disease.

Key Messages/Clinical Perspectives

  • Based on the results of CREDENCE, the American Diabetes Association recently updated the Standards of Care with renal guidance, stating that “For patients with type 2 diabetes and diabetic kidney disease, consider use of an SGLT2 inhibitor in patients with an eGFR ≥30 mL/min/1.73m2 and particularly in those with >300 mg/g albuminuria to reduce risk of CKD progression, cardiovascular events, or both.”

 

Trial: NCT02065791



References

References


  1. Mahaffey KW, Jardine MJ, Bompoint S, et al. Canagliflozin and cardiovascular and renal outcomes in type 2 diabetes mellitus and chronic kidney disease in primary and secondary cardiovascular prevention groups. Circulation 2019 Aug 27;140(9):739-50
  2. Perkovic V, Jardine MJ, Neal B, et al. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019 Jun 13;380(24):2295-306

Presenter disclosure: The presenters has reported the follow relationships: C. Pollock: Pharmaxis Pty Ltd, Johnson & Johnson, Boehringer Ingelheim, AstraZenca, Novartis, Merchk Sharpe & Dohme, Otsuka, Eli Lilly. H.L. Heerspink: AstraZenca, Boehringer Ingelheim, Janssen, CSL Pharma, Gilead, Merck, Mitsubishi Tanabe, Retrophin. K. Mahaffey: Afferent, Amgen, Apple Inc., AstraZeneca, Cardiva Medical Inc., Daiichi, Johnson & Johnson, Liutpold, Medtronic, Merck, NIH, Novartis, Abbott, Ablynx, Baim Institute, Boehringer Ingelheim, Bristol Myers Squibb, GlaxoSmithKline, MedErgy, Medscape, Mitsubishi, Novartis, Novo Nordisk, Portola, Radiometer, Regeneron, Springer Publishing, UCSF

Medical writer: Patrick Moore, PhD

Reviewer: Marco Gallo, MD

Local reviewers: Marco Gallo, MD (Italia); Anna Novials Sardá, MD, PhD (España); Eric Renard, MD, PhD (France); Peter Schwarz, MD, PhD (Deutschland) 

Scientific Editor: Florian Toti, MD


CLINICAL TRIALS

T2D & NEPHROPATY

CREDENCE – Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

Presented by: Carol Pollock, MBBS, PhD, FRACP, AAHMS; Hiddo Lambers Heerspink, PharmD, PhD; Kenneth W. Mahaffey, MD

PREVENTION

Results from the Anti-CD3 mAb (teplizumab) prevention trial

Presented by: Kevan Herold, MD; Peter S. Linsley, PhD

DIABETES & CVD

DECLARE study: call for action

Presented by: Itamar Raz, MD; Ofri Mosenzon, MD, MSc; Avivit Cahn, MD

T2D TREATMENT

VERIFY – Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes

Presented by: Chantal Mathieu, MD; Michael Stumvoli, MD; David R. Matthews, MD; Stefano del Prato, MD

DIABETES & HF

DAPA-HF: dapagliflozin and prevention of adverse-outcomes in heart failure

Presented by: Mikhail Kosiborod, MD; Silvio Inzucchi, MD

CV SAFETY

Results and implications of CAROLINA (CARdiOvascular Safety of LINAgliptin) comparing linagliptin vs glimepiride

Presented by: Julio Rosenstock, MD; Mark A. Espeland, MD; Steven E. Kahn, MD; Nikolaus Marx, MD; Bernard Zinman, MD; Darren McGuire, MD

T2D & CV PREVENTION

T1D DETERMINANTS

The Environmental Determinants of Diabetes in the Young (TEDDY) study

Presented by: Anette-Gabriele Ziegler, MD; Heikki Hyöty, MD, PhD
 

SYMPOSIA

NAFLD & DIABETES

EASD/EASL Symposium: is NAFLD a risk for health in the context of diabetes?

Presented by: Michael Roden, MD; Stefano Romeo, MD; Elisabetta Bugianesi, MD, PhD

HF & T2D

EASD/ESC Symposium: heart failure in type 2 diabetes

Presented by: M. Louis Handoko, MD; Javed Butler, MD, MPH, MBA

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