lotiglipron + itraconazole

Lotiglipron + itraconazole is a combination of two oral pharmaceuticals: lotiglipron, a potent, selective, small-molecule agonist of the glucagon-like peptide-1 receptor (GLP-1R), and itraconazole, a triazole antifungal agent. Lotiglipron was developed for treatment of Type 2 diabetes and obesity, intended to provide metabolic benefits by activation of GLP-1R, which results in improved glycemic control and weight loss through increased insulin secretion and delayed gastric emptying.[2][4] Itraconazole is most frequently used to treat systemic and superficial fungal infections via inhibition of fungal cytochrome P450 14α-demethylase, blocking ergosterol synthesis in fungal membranes.[1] In a clinical pharmacokinetic interaction study, co-administration of lotiglipron with itraconazole resulted in a markedly increased blood exposure to lotiglipron (2.8-fold increase), due to itraconazole's well-known inhibition of CYP3A4-mediated metabolism. This interaction has safety implications, as increased lotiglipron levels may enhance efficacy or adverse effects. Lotiglipron's development was discontinued due to safety concerns about liver transaminase elevations, and the drug is not marketed.[2][4][6] No therapeutic indication is established for the specific combination of lotiglipron + itraconazole beyond drug-drug interaction studies.