Adverse events and drug-drug interactions of sodium glucose co-transporter 2 inhibitors in patients treated for heart failure.

INTRODUCTION: Sodium glucose co-transporter 2-inhibitors (SGLT2-I), antihyperglycemic agents, are increasingly prescribed in chronic heart failure (CHF). Their risk for drug-drug interactions (DDI) seems low. Safety-data derive mainly from diabetes-patients. This review aims to summarize adverse-events (AE) and DDI of the SGLT2-I dapagliflozin, empagliflozin and sotagliflozin in patients with CHF.

AREAS COVERED: Literature-search-terms in PubMed were 'adverse event/drug-drug interaction' and 'heart failure AND 'dapagliflozin' OR 'empagliflozin' OR 'sotagliflozin.'AEreported in randomized controlled trials (RCT) comprisegenitaland urinary-tract infections, hypotension, ketoacidosis, renal impairment, hypoglycemia, limb-amputations, Fournier's gangrene, bone-fractures, hepatopathy, pancreatitis, diarrhea, malignancy and venous thromboembolism. Their incidence is largely unknown, since they were not consistently evaluated in RCT of CHF. Further AE from meta-analyses, pharmacovigilance reports, case-series and case-reports include erythrocytosis, hypertriglyceridemia, myopathy, sarcopenia, skin problems, ventricular tachycardia, and urinary retention. The maximal observation period of RCT in CHF was 26 months.DDI were mainly studied in healthy volunteers for 3-8 days. In CHF or diabetes-patients, DDI were reported with interleukin-17-inhibitors, linezolid, lithium, tacrolimus, valproate, angiotensin-receptor-neprilysin-inhibitors and intravenous iron.

EXPERT OPINION: Guidelines recommend treatment with SGLT2-I for CHF but no data on AE during long-term therapy and only little information on DDI are available, which stresses the need for further research. Evidence-based recommendations for ketoacidosis-prevention are desirable.