Table 3.

Possible pharmacokinetic interactions between bedaquiline/delamanid and hypoglycemic agents and their expected clinical effects

Interaction level	Possible pharmacokinetics	Expected clinical effects
Transporter level (ABCB1)	Inhibition of SU and SGLT-2 inhibitors	Lack of hypoglycemic efficacy
Protein-binding level	Competition for protein-binding sites (bedaquiline/delamanid vs SU, glinides, SGLT-2 inhibitors)	Unclear
Hepatic metabolism level	Decreased exposure to bedaquiline/delamanid with strong CYP3A4 inducers (bromocriptine)	Lack of antituberculosis efficacy
	Increased exposure to oral hypoglycemic agents mainly metabolized by CYP3A4 (nateglinide, sitagliptin, saxagliptin) due to inhibitory effect of M2	Hypoglycemic episodes
	Increased exposure to bedaquiline in severe infection (downregulation of P450 expression)	Toxicity of bedaquiline
	Increased exposure to oral hypoglycemic agents in severe infections (downregulation of P450 expression)	Hypoglycemic episodes

Note: ABCB1 is a P-glycoprotein, and M2 is the bedaquiline metabolite.

Abbreviation: SU, sulfonylureas.