Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes: a systematic review and meta-analysis of randomised placebo-controlled trials

Wan Chuan Tsai, Shih Ping Hsu, Yen Ling Chiu, Ju Yeh Yang, Mei Fen Pai, Mei Ju Ko, Yu Kang Tu, Kuan Yu Hung, Kuo Liong Chien, Yu Sen Peng, Hon Yen Wu

Research output: Contribution to journalReview articlepeer-review

26 Citations (Scopus)

Abstract

Objectives To assess the cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients without diabetes. Methods We searched PubMed, MEDLINE, Embase and Cochrane Library for publications up to 17 August 2022. Certainty of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation approach. Random-effects meta-analyses were performed to pool effect measures across studies. Risk ratios (RRs) with 95% CIs are expressed for composite cardiovascular outcome of cardiovascular death or hospitalisation for heart failure, cardiovascular death, hospitalisation for heart failure, all-cause mortality and composite renal outcome of ≥50% reduction in estimated glomerular filtration rate (eGFR), end-stage kidney disease or renal death. Annual rate of change in eGFR is expressed as the mean difference with 95% CI. Results We identified four trials with 8927 patients with heart failure or chronic kidney disease (CKD). Compared with placebo, SGLT2 inhibitors showed favourable effects on the composite cardiovascular outcome (RR: 0.79, 95% CI: 0.71 to 0.87; moderate certainty), cardiovascular death (0.85, 0.74 to 0.99; moderate certainty), hospitalisation for heart failure (0.72, 0.62 to 0.82; moderate certainty), the composite renal outcome (0.64, 0.48 to 0.85; low certainty) and the annual rate of change in eGFR (mean difference: 0.99, 0.59 to 1.39 mL/min/1.73 m 2 /year; moderate certainty), while there was no significant difference in all-cause mortality (0.88, 0.77 to 1.01; very low certainty). Moderate certainty evidence indicated that SGLT2 inhibitors reduced the risk of serious adverse events and acute renal failure. Low certainty evidence suggested that SGLT2 inhibitors increased the risk of urinary tract infection and genital infection, while there were no differences in discontinuation due to adverse events, amputation, fracture, hypoglycaemia, ketoacidosis or volume depletion. Conclusions Evidence of low to moderate certainty suggests that SGLT2 inhibitors provide cardiorenal benefits but have increased risk for urinary tract infection and genital infection in patients without diabetes and with heart failure or CKD. PROSPERO registration number CRD42021239807.

Original languageEnglish
Article numbere060655
JournalBMJ Open
Volume12
Issue number10
DOIs
Publication statusPublished - Oct 14 2022
Externally publishedYes

Keywords

  • cardiology
  • chronic renal failure
  • diabetic nephropathy & vascular disease
  • heart failure
  • nephrology

ASJC Scopus subject areas

  • General Medicine

Fingerprint

Dive into the research topics of 'Cardiovascular and renal efficacy and safety of sodium-glucose cotransporter-2 inhibitors in patients without diabetes: a systematic review and meta-analysis of randomised placebo-controlled trials'. Together they form a unique fingerprint.

Cite this