Potential drug-drug interaction between sodium-glucose co-transporter 2 inhibitors and statins: pharmacological and clinical evidence.
INTRODUCTION
Recent case reports suggested that concomitant use of sodium-glucose co-transporter 2 (SGLT2) inhibitors with statins could lead to increased statin toxicity. We provide a comprehensive overview of the available pharmacological and clinical evidence on this potential drug-drug interaction (DDI).


AREAS COVERED
We searched MEDLINE PubMed until November 2020 for (i) pharmacokinetic studies on SGLT2 inhibitors, statins, and their potential interaction, and (ii) case reports and clinical studies assessing the safety of concomitant use of SGLT2 inhibitors and statins. We also searched regulatory documents submitted to the United States Food and Drug Administration for unpublished data on this potential DDI.


EXPERT OPINION
SGLT2 inhibitors are increasingly used for type 2 diabetes, chronic heart failure, and chronic kidney disease, and concomitant use with statins is common given the comorbidity of indications. While pharmacokinetic studies in healthy subjects showed no clinically relevant changes in statin levels during SGLT2 inhibitor co-administration, the published case reports and pharmacologic reasoning support the possibility of an interaction. Underlying mechanisms could be pharmacokinetic or pharmacodynamic, and canagliflozin appears to be the SGLT2 inhibitor with the highest interaction potential. Further research including 'real-world' pharmacoepidemiologic studies is needed to better understand the clinical significance of this DDI.
['Lalagkas|Panagiotis-Nikolaos|PN|https://orcid.org/0000-0002-8245-1758', 'Poulentzas|Georgios|G|https://orcid.org/0000-0002-5909-3526', 'Kontogiorgis|Christos|C|https://orcid.org/0000-0001-7835-8246', 'Douros|Antonios|A|https://orcid.org/0000-0002-6005-4006']
D000068896:Canagliflozin D003924:Diabetes Mellitus, Type 2 D004347:Drug Interactions D006333:Heart Failure D006801:Humans D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors D051436:Renal Insufficiency, Chronic D000077203:Sodium-Glucose Transporter 2 Inhibitors
sodium-glucose co-transporter 2 inhibitors pharmacology clinical evidence Drug–drug interaction