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Evidence-Based Diabetes Management June 2019

2019 ADA Coverage: Renal Outcomes

Mary Caffrey
Coverage of DECLARE, CARMELINA, and other studies that highlight the connection between diabetes and renal outcomes
Last November, investigators reported a 24% decline in a composite of cardiorenal measures for patients taking dapagliflozin.7 At the 79th Scientific Sessions, they reported that patients taking dapagliflozin had a 47% reduction compared with placebo in the relative risk of a composite renal outcome, which included kidney function decline, defined as sustained ≥40% decrease in estimated glomerular filtration rate (eGFR) to <60 mL/min/1.73m2; ESRD; and renal death. The difference was 1.5% versus 2.8%; (hazard ratio [HR], 0.53; 95% CI, 0.43-0.66; P = .0001).1 ​​​​​​​

This result was driven by a 46% reduction in kidney function decline, as there were relatively few incidents of ESRD or renal death: 11 (0.1%) in the dapagliflozin group compared with 27 (0.3%) in the placebo group. The authors noted that preservation of renal function with dapagliflozin was seen across subgroups. Although there was a decline in eGFR in the dapagliflozin group relative to placebo after 6 months, this difference was eliminated after 2 years; at years 3 and 4, the mean decrease in eGFR was less with dapagliflozin. 

“In both aspects, when you look at the renal by itself or the cardiorenal, you see great benefit when you [use] Farxiga in this patient population,” Khan said. “That’s not only the people with established cardiovascular disease but also the people with multiple risk factors. And that’s the kind of patient population the physician actually sees in the office.” 

Khan pointed out that most study participants had good renal health at baseline, yet taking dapagliflozin made a significant difference in their long-term outcomes. Of the group, 47.6% had a baseline eGFR of at least 90 mL/min/1.73m2, which is normal renal function, and another 45.1% had an eGFR of 60 to <90 mL/min/1.73m2

“These are results we saw in a broad range of patient population that actually had a mean eGFR of 85 [mL/min/1.73m2]. That’s quite a healthy kidney, and yet we saw these benefits,” Khan said. “This is stage 1 [CKD] and earlier,” he added. 

“It’s very impactful to look at how healthy the kidney was when they were getting the treatment,” Khan said. This points to how much damage diabetes can do to the renal system in a relatively short period. 

As CVOTs for the SGLT2 inhibitor class demonstrated the drugs’ ability to slow renal decline, makers of these therapies launched dedicated renal outcomes studies. In March, investigators for the first such study, CREDENCE, for canagliflozin, reported a 30% reduction in renal failure or death for patients with T2D and CKD.9 The renal outcomes study for dapagliflozin, Dapa-CKD, is under way and has an estimated completion of November 2020.2

 There has been speculation that as SGLT2 inhibitors gain new indications and find their way into guidelines outside of diabetes—the ACC now recommends the class in primary prevention—there will be greater use by patients newly diagnosed with diabetes. 

Along with the results for Dapa-HF, a dedicated heart failure trial due to report later this year, this evidence “should give the primary care physician the confidence to treat more aggressively earlier in diabetes,” Combs said. The results should also give specialists such as cardiologists the confidence to treat comorbidities seen in patients with diabetes, she said. 

REFERENCES:
  1. Mosenzon O, Wiviott SD, Cahn A, et al. 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 [published online June 10, 2019]. Lancet Diab Endocrinol. doi: 10.1016/ S2213-8587(19)30180-9. 
  2. A Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (Dapa-CKD). clinicaltrials.gov/ct2/show/NCT03036150. Updated April 29, 2019. Accessed June 16, 2019. 
  3. Kidney disease statistics for the United States. National Institute for Diabetes and Digestive and Kidney Diseases website. www.niddk.nih.gov/ health-information/health-statistics/kidney-disease. Published December 2016. Accessed June 16, 2019. 
  4. Narres M, Claessen H, Droste S, et al. The incidence of end-stage renal disease in the diabetic (compared to the non-diabetic) population: a systematic review. PLoS One. 2016;11(1):e0147329. doi: 10.1371/journal.pone.0147329. 
  5. United States Renal Data System. Annual Data Report 2018. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases; 2018. 
  6. Zinman B, Wanner C, Lachin JM, et al; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117-2126. doi: 10.1056/NEJMoa1504720. 
  7. Wiviott SD, Raz I, Bonaca MP, et al; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in diabetes. N Engl J Med. 2019;380(4):347-357. doi: 10.1056/NEJMoa1812389. 
  8. Kato ET, Silverman MG, Mosenzon O, et al. Effect of dapagliflozin on heart failure and mortality in type 2 diabetes mellitus. Circulation. 2019;139(22):2528-2536. doi: 10.1161/CIRCULATIONAHA.119.040130. 
  9. Perkovic V, Jardine MJ, Neal B, et al; CREDENCE Trial Investigators. Canagliflozin and renal outcomes in type 2 diabetes and nephropathy. N Engl J Med. 2019;380(24):2295-2306. doi: 10.1056/NEJMoa1811744. 


 
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