Drug Interactions of SGLT2 Inhibitors (Gliflozins) Involving UGT Enzymes

Sodium glucose cotransporter 2 (SGLT2) inhibitors are antidiabetic drugs which are useful in the management of blood sugar of patients with type 2 diabetes, along with diet and exercise. The SGLT2 inhibitors are the substrates of UGT enzymes and SGLT2 inhibitorss uch as Dapagliflozin, Canagliflozin and Ipragliflozin are metabolised by glucuronidation predominantly by UGT1A9 enzyme. In addition, Canagliflozin and Ipragliflozin are also metabolised by UGT2B4. The drugs inhibiting or inducing UGT1A9 and other UGT enzymes are expected to alter the pharmacokinetics of SGLT2 inhibitors. Although the plasma exposure of Dapagliflozin and Canagliflozin are increased slightly by the concomitant use of Mefenamic acid and Probenecid respectively, these interactions were not considered clinically meaningful. Rifampicin and other UGT inducers such as Phenytoin, Phenobarbital and Ritonavir were observed to decrease the plasma levels of Canagliflozin, insignificantly. Based on the results of this review, SGLT2 inhibitors could be coadministered with any medicines without dosage adjustments except Canagliflozin, which needs higher dosage while using along with UGT enzyme inducers.

Keywords: Drug interactions; SGLT2 inhibitors; UGT Enzymes; Canagliflozin; Dapagliflozin; Empagliflozin; Ertugliflozin; Ipragliflozin; Luseogliflozin; Tofogliflozin.