The safety outcomes of sodium-glucose cotransporter 2 inhibitors in patients with different renal function: A systematic review and meta-analysis

Nutr Metab Cardiovasc Dis. 2021 May 6;31(5):1365-1374. doi: 10.1016/j.numecd.2021.02.006. Epub 2021 Feb 13.


Aims: We aimed to assess whether the safety outcomes exerted by sodium-glucose cotransporter 2 (SGLT2) inhibitors were associated with different renal function at baseline.

Data synthesis: We searched randomized controlled trials comparing SGLT2 inhibitors with placebo in participants simultaneously involving the entire range of estimated glomerular filtration rate (eGFR) levels at baseline in one study. According to eGFR, we divided the population into two subgroups with eGFR <60 ml/min/1.73 m2 and eGFR≥60 ml/min/1.73 m2. Data from the CANVAS program, CREDENCE, EMPA-REG OUTCOME, DECLARE-TIMI 58, DAPA-HF, and EMPA-REG RENAL were included. SGLT2 inhibitors significantly reduced the risk of all serious adverse events (HR 0.91 [95% CI 0.87 to 0.95], p < 0.001) and acute kidney injury (HR 0.74 [95% CI 0.64 to 0.85], p < 0.001). Except for high risk of genital infection, SGLT2 inhibitors did not increase the risk of amputation, fracture, hyperkalemia, hypoglycemia, volume depletion, or urinary tract infection. Further analyses showed that these safety outcomes were similar between subgroups (p-interaction > 0.05). For osmotic diuresis, SGLT2 inhibitors significantly increased the risk by 75% (p = 0.036), and subgroup analyses showed that this effect was completely attributed to the increase in patients with eGFR ≥60 ml/min/1.73 m2 (p-interaction<0.001).

Conclusion: The indication of no risk of osmotic diuresis in patients with eGFR<60 ml/min/1.73 m2 and the consistency of other safety outcomes across different baseline renal function may allow additional individuals to safely use SGLT2 inhibitors.

Keywords: Meta-analysis; Renal function; SGLT2 inhibitors; Safety.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Aged
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / epidemiology
  • Female
  • Glomerular Filtration Rate / drug effects*
  • Humans
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Kidney Diseases / diagnosis
  • Kidney Diseases / epidemiology
  • Kidney Diseases / physiopathology*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*
  • Treatment Outcome


  • Sodium-Glucose Transporter 2 Inhibitors