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

Oct 14, 2022BMJ open

Heart and kidney benefits and safety of sodium-glucose cotransporter-2 inhibitors in people without diabetes

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Abstract

may reduce the composite cardiovascular outcome by 21% compared to placebo in patients without diabetes.

SGLT2 inhibitors are associated with a 15% reduction in cardiovascular death compared to placebo.
Hospitalization for heart failure may be reduced by 28% with SGLT2 inhibitor use.
The composite renal outcome could be improved, showing a 36% reduction in risk.
SGLT2 inhibitors may result in an average annual increase in kidney function of 0.99 mL/min/1.73 m².
There is moderate certainty that SGLT2 inhibitors decrease the risk of serious adverse events and acute renal failure.

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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 (), 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, 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/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. 2

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.

Key numbers

0.79

Reduction in Composite Cardiovascular Outcome

Risk ratio comparing to placebo for composite cardiovascular outcomes.

0.99 mL/min/1.73 m/year

Annual Rate of Change in

Mean difference in decline between and placebo.

2.44

Increased Risk of Genital Infection

Risk ratio for genital infections in patients treated with compared to placebo.

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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

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