Will SGLT2 Inhibitors Be Effective and Safe in Patients with Severe CKD, Dialysis, or Kidney Transplantation
Abstract
The clinical benefits of sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in patients with CKD have been well established in major clinical outcome trials.1,2 Secondary analyses from these landmark trials demonstrated consistent benefits of SGLT2 inhibitors across many subgroups, supporting the widespread use and incorporation in clinical practice guidelines of this new kidney and cardioprotective drug class.3,4 Notwithstanding, there are three important groups of kidney patients in whom SGLT2 inhibitors are not indicated. First are patients with severely impaired kidney function. This seems sensible because the efficacy of SGLT2 inhibitors in these patients could well be diminished. SGLT2 inhibitors block the reabsorption of glucose and sodium in the proximal tubule and enhance glycosuria and natriuresis. In patients with a low number of functioning nephrons, it may be expected that SGLT2 transporters are less effective because the number of SGLT2 transporters containing tubules is reduced. Therefore, patients with an eGFR 25 (DAPA-CKD; N=624) or >20 ml/min per 1.73 m2 (EMPA-Kidney; N=2282).1,2 In both trials, SGLT2 inhibition reduced the risk of the primary kidney outcome by 27% with no evidence that the magnitude of the effect estimate varied by baseline GFR. Moreover, in the DAPA-CKD trial, dapagliflozin reduced the relative risks of heart failure or cardiovascular death or all-cause mortality, both secondary outcomes, in participants with and without CKD stage 4.1 In…
How strong is the evidence?
Evidence Hub reads this as a randomized trial, done in people. Its evidence level is 2 of 5 (High · randomized trial). Randomized trials of a reasonable size are the strongest single-study design. Reported size: 2,906 participants or records.
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