Plazomicin + Metformin

Plazomicin + Metformin does not represent a single biological target but rather a combination of two distinct pharmacological agents with a significant clinical interaction. Plazomicin is a next-generation aminoglycoside antibiotic used to treat complicated urinary tract infections (cUTI) by binding to the bacterial 30S ribosomal subunit and disrupting protein synthesis (PubMed, 2019). Metformin is a biguanide medication and the first-line treatment for type 2 diabetes, acting primarily to decrease hepatic glucose output and improve insulin sensitivity through AMPK activation (NIH, 2023). The clinical relevance of this pair arises because plazomicin is an inhibitor of the Multidrug and Toxin Extrusion (MATE1 and MATE2-K) transporters in the kidney (Zemdri Prescribing Information, 2018). Since metformin is a substrate for these transporters, co-administration can lead to reduced metformin clearance and increased systemic concentrations. This interaction significantly elevates the risk of metformin-associated lactic acidosis, a rare but serious metabolic complication, particularly in patients with underlying renal impairment.

Other names

Plazomicin and Metformin combinationZemdri and Glucophage

Plazomicin inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit (FDA, 2018). Metformin reduces hepatic glucose production by inhibiting mitochondrial complex I and activating AMPK (StatPearls, 2023). Additionally, plazomicin inhibits MATE1 and MATE2-K transporters, which are responsible for the renal secretion of metformin, thereby increasing metformin exposure.