Clinical question
How do sodium-glucose cotransporter-2 inhibitors (SGLT2Is) affect patient outcomes in chronic kidney disease (CKD)?
Bottom line
For every 100 patients with CKD taking an SGLT2I for 5 years, approximately 3 or 4 fewer will develop end-stage kidney disease and 3 to 4 fewer will die from any cause versus placebo. Sotagliflozin is not better than placebo for these outcomes.
Evidence
Results were statistically significant unless noted.
Two systematic reviews of relevant RCTs included patients with CKD.1,2
- In 1 review of 52,827 patients with cardiovascular and CKD risks, among those with CKD at 5 years1:
— End-stage kidney disease: 8.9% vs 12% (placebo), number needed to treat (NNT)=33.
— Cardiovascular death: 11% vs 14% (placebo), NNT=27.
— Overall mortality: 19% vs 22% (placebo), NNT=31.
- In the other review (8 RCTs) involving 26,106 patients with baseline CKD, at 2.5 years2:
— Cardiovascular disease: 10% vs 11% (placebo), NNT=91.
— Composite kidney outcome (40% to 60% estimated glomerular filtration rate decline, end-stage kidney disease, or renal death): 4.8% vs 6.9% (placebo), NNT=48.
- Limitations: included RCTs not specific to CKD patients.
In 3 industry-funded RCTs (with CKD patients),3-5 mean estimated glomerular filtration rate was about 40 to 55 mL/min/1.73 m2, albumin-to-creatinine ratio was about 75 to 105 mg/mmol, and 67% to 100% of patients had diabetes.
- In a trial of 4401 patients taking 100 mg of canagliflozin daily,3 at 2.6 years:
— End-stage kidney disease: 5.3% vs 7.5% (placebo), NNT=45.
— Cardiovascular death: 5.0% vs 6.4% (placebo), NNT=71.
— All-cause mortality: 7.6% vs 9.1% (placebo), NNT=67.
- In another trial of 4304 patients taking 10 mg of dapagliflozin,4 at 2.4 years:
— End-stage kidney disease: 5.1% vs 7.5% (placebo), NNT=42.
— Cardiovascular death: 3.0% vs 3.7% (placebo), not statistically different.
— All-cause mortality: 4.7% vs 6.8% (placebo), NNT=48.
- In a third trial of 10,584 patients taking 200 mg to 400 mg of sotagliflozin daily,5 at 1.3 years:
— No differences in composite kidney outcome, cardiovascular death, or all-cause mortality.
Context
Metformin and SGLT2Is are recommended first-line therapies for those with type 2 diabetes and CKD.6
Implementation
On average, SGLT2Is lower systolic blood pressure by about 4 mm Hg in those with CKD taking renin-angiotensin-aldosterone system blockers.7 Hemoglobin A1c reductions of about 0.3% are seen in patients with CKD initiating SGLT2I therapy (most already using metformin, insulin, or sulphonylureas), while reductions of up to 0.6% or 1.0% are seen in patients with diabetes with less intensive background antihyperglycemic therapy.7,8 To add an SGLT2I, existing non–renin-angiotensin-aldosterone antihypertensives or antihyperglycemics may need to be minimized.6
Notes
Tools for Practice articles in CFP are adapted from peer-reviewed articles at http://www.toolsforpractice.ca and summarize practice-changing medical evidence for primary care. Coordinated by Dr G. Michael Allan and Dr Adrienne J. Lindblad, articles are developed by the Patients, Experience, Evidence, Research (PEER) team and supported by the College of Family Physicians of Canada and its Alberta, Ontario, and Saskatchewan Chapters. Feedback is welcome at toolsforpractice{at}cfpc.ca.
Footnotes
Competing interests
None declared
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La traduction en français de cet article se trouve à https://www.cfp.ca dans la table des matières du numéro d’octobre 2022 à la page e283.
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