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#319 Should a ‘flozin’ be chosen? Part 2: SGLT2 inhibitors in patients with chronic kidney disease


CLINICAL QUESTION
QUESTION CLINIQUE
What are the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on patient-relevant outcomes in chronic kidney disease (CKD)?


BOTTOM LINE
RÉSULTAT FINAL
For every 100 patients with CKD treated with an SGLT2i for 5 years, ~3-4 fewer will develop end-stage kidney disease (ESKD) and ~3-4 fewer will die from any cause compared to placebo. Sotagliflozin is not better than placebo for these outcomes



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EVIDENCE
DONNÉES PROBANTES
  • Two systematic reviews of relevant randomized, placebo-controlled trials (RCTs) included patients with CKD.1,2 Results statistically different unless noted.
    • 52,827 patients with various cardiovascular/CKD risk. Of those with CKD, at 5 years:1
      • ESKD: 8.9% versus 12% (placebo), number needed to treat (NNT)=33.
      • Cardiovascular death: 11% versus 14% (placebo), NNT=27.
      • Overall mortality: 19% versus 22% (placebo), NNT=31.
    • 8 RCTs, 26,106 patients with baseline CKD, at 2.5 yrs:2
      • Cardiovascular disease: 10% versus 11% (placebo), NNT=91.
      • Composite kidney outcome (40-60% eGFR decline, ESKD, or renal death): 4.8% versus 6.9% (placebo), NNT=48.
    • Limitations: Included RCTs not specific to CKD patients.
  • Three industry-funded RCTs3,4,5 specific to CKD patients (neither above review included all 3 in every outcome). Mean eGFR~40-55ml/min/1.73m2, albumin-to-creatinine ratio ~75-105mg/mmol, 67-100% had diabetes.
    • CREDENCE:3 4,401 patients, canagliflozin 100mg daily. At 2.6 years:
      • ESKD: 5.3% versus 7.5% (placebo), NNT=45.
      • Cardiovascular death: 5.0% versus 6.4% (placebo), NNT=71.
      • All-cause mortality: 7.6% versus 9.1% (placebo), NNT=67.
    • DAPA-CKD:4 4,304 patients, dapagliflozin 10mg daily. At 2.4 years:
      • ESKD: 5.1% versus 7.5% (placebo), NNT=42.
      • Cardiovascular death: 3.0% versus 3.7% (placebo), not statistically different.
      • All-cause mortality: 4.7% versus 6.8% (placebo), NNT=48.
    • SCORED:5 10,584 patients, sotagliflozin 200-400mg daily. At 1.3 years:
      • No difference in composite kidney outcome, cardiovascular death, or all-cause mortality.
    • Adverse events:3-5
      • Increase in genital infections [number needed to harm (NNH) 59-67], volume depletion (NNH=59-77), and DKA (NNH=220 to not statistically significant).
  • One meta-analysis of DAPA-CKD and CREDENCE only. At ~2.5 years:6
    • ESKD: 5.2% versus 7.5% (placebo).
    • Cardiovascular death: 4% versus 5% (placebo).
Context
  • EMPA-KIDNEY trial stopped early for benefit.7,8
  • Guidelines9 recommend metformin and SGLT2i first-line for patients with type-2 diabetes and CKD.
  • Cost: ~$90/month.10


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Author(s)
Auteur(s)
  • Jamie Falk BSc(Pharm) PharmD
  • Scott Klarenbach MD FRCPC
  • Cynthia Lam PharmD ACPR
  • Jennifer Potter MD CCFP

1. Palmer SC, Tendal B, Mustafa RA, et al. BMJ. 2021; 372:m4573.

2. Kaze AD, Zhuo M, Kim SC, et al. Cardiovasc Diabetol. 2022; 21:47.

3. Perkovic V, Jardine MJ, Neal B, et al. N Engl J Med. 2019; 380:2295-2306.

4. Heerspink HJL, Stefánsson BV, Correa-Rotter R, et al. N Engl J Med. 2020; 383:1436-1446.

5. Bhatt DL, Szarek M, PittB, et al. N Engl J Med. 2021; 384:129-39.

6. Patoulias D, Papdopoulos C, Stavropoulos K, et al. Am J Cardiol. 2021; 138:116-132.

7. ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT03594110 [accessed 2022 June 15].

8. Boehringer Ingelheim https://www.boehringer-ingelheim.com/human-health/metabolic-diseases/early-stop-chronic-kidney-disease-trial-efficacy [accessed 2022 June 15].

9. de Boer IH, Caramori ML, Chan JCN, et al. Kidney Int. 2020; 98:839–848.

10. PEER/Alberta College of Family Physicians Price Comparison of Commonly Prescribed Pharmaceuticals in Alberta 2022. Available at: https://pricingdoc.acfp.ca/pricing/clickable-table/?cat=Hypoglycemic%20Agents [accessed 2022 Jun 21].

Authors do not have any conflicts of interest to declare.

Les auteurs n’ont aucun conflit d’intérêts à déclarer.