Back The CREDENCE study – adding yet more to the existing cardiovascular outcomes studies with SGLT2 inhibition 2019
Bev Bostock RGN MSc MA Queen’s Nurse
Nurse Practitioner Mann Cottage Surgery Gloucestershire
PCCS nurse board member
Renal impairment, including end stage renal disease is a major concern in the management of diabetes and has a significant impact on patients, their families and resources1,2. It is estimated that the need for dialysis (which is very costly, has a negative impact on quality of life and has a poor prognosis) is set to rise from 3 million to 5 million people worldwide by 2035, especially with the increasing prevalence of diabetes3. The CREDENCE study, which was stopped early based on a planned interim analysis and on the recommendation of the safety committee, showed that using 100mg of canagliflozin, an SGLT2 inhibitor, reduced the risk of end-stage kidney disease or death from renal or cardiovascular causes by 30% when compared with placebo4. Canagliflozin, in line with other SGLT2 inhibitors, also has a very positive effect on cardiovascular disease and heart failure, something that had already been highlighted in previous cardiovascular outcomes studies5,6,7. Importantly, there was also a strong safety signal, with no increase in amputations or fracture in the treated group. This is the first study to confirm that an SGLT2 inhibitor (specifically canagliflozin 100mg) on top of the maximum tolerated dose of ACE inhibitor or ARB can have a positive impact on renal impairment.
It remains to be seen how quickly a licence change will follow as currently SGLT2 inhibitors can only be initiated in people with an eGFR >60ml/min, although they can be continued if the eGFR drops after this, up to 45ml/min, at which point they should be stopped. The data from CREDENCE begs consideration of off licence prescribing in the meantime.
Excerpt from study:
4401 patients had undergone randomization, 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 (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001).
1 Jha V et al (2018) Ethical issues in dialysis therapy. Lancet, 389 (10081) p1851-56
2 Dąbrowska-Bender M et al (2018). The impact on quality of life of dialysis patients with renal insufficiency. Patient preference and adherence, 12, 577–583
3 Lyanage T et al (2015) Worldwide access to treatment for end-stage kidney disease Lancet 385:1975-82
4 Perkovic V et al (2019) Canagliflozin and Renal Outcomes in Type 2 diabetes and Nephropathy NEJM
5 Neal B et al (2017) Canagliflozin and cardiovascular and renal events in type 2 diabetes NEJM 337:644-57
6 Zinman B et al (2015) Empagliflozin cardiovascular outcomes and mortality in type 2 diabetes NEJM 373:2117-28
7 Wiviott SD et al (2019) Dapagliflozin cardiovascular outcomes in type 2 diabetes NEJM 380:347-57