Lack of Drug-Drug Interaction Between Cimetidine, a Renal Transporter Inhibitor, and Imeglimin, a Novel Oral Antidiabetic Drug, in Healthy Volunteers

Eur J Drug Metab Pharmacokinet. 2020 Dec;45(6):725-733. doi: 10.1007/s13318-020-00642-4.


BACKGROUND AND OBJECTIVE: Imeglimin is a novel oral antidiabetic drug to treat type 2 diabetes, targeting the mitochondrial bioenergetics. In vitro, imeglimin was shown to be a substrate of human multidrug and toxic extrusion transporters MATE1 and MATE2-K and organic cation transporters OCT1 and OCT2. The objective of the study was to assess the potential drug-drug interaction between imeglimin and cimetidine, a reference inhibitor of these transporters.

Methods: A phase 1 study was carried out in 16 subjects who received a single dose of 1500 mg imeglimin alone on day 1 followed by a 6-day treatment (day 5 to day 10) with cimetidine 400 mg twice daily. On day 8, a single dose of imeglimin was co-administered with cimetidine. Blood and urine samples were collected up to 72 h after each imeglimin administration. Pharmacokinetic parameters were determined using non-compartmental methods.

Results: Imeglimin maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were 1.3-fold [90% CI (1.12-1.62) and (1.10-1.46) for Cmax and AUC0-last, respectively] higher when imeglimin was co-administered with cimetidine but this increase was not considered clinically relevant. This increase could be mainly explained by a reduction in renal elimination, mediated through the cimetidine inhibition of renal MATE1 transporter. Imeglimin taken alone or with cimetidine was safe and well tolerated in all subjects.

Conclusions: No clinically significant drug-drug interaction exists between imeglimin and cimetidine, a reference inhibitor of MATE1, MATE2-K, OCT1 and OCT2 transporters.

Clinical trial registration: EudraCT 2018-001103-36.

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Area Under Curve
  • Cimetidine / pharmacology*
  • Drug Interactions
  • Female
  • HEK293 Cells
  • Healthy Volunteers
  • Histamine H2 Antagonists / pharmacology*
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Kidney / drug effects
  • Kidney / metabolism*
  • Male
  • Middle Aged
  • Octamer Transcription Factor-1 / antagonists & inhibitors
  • Octamer Transcription Factor-1 / metabolism
  • Organic Cation Transport Proteins / antagonists & inhibitors
  • Organic Cation Transport Proteins / metabolism
  • Organic Cation Transporter 2 / antagonists & inhibitors
  • Organic Cation Transporter 2 / metabolism
  • Triazines / pharmacokinetics*
  • Young Adult


  • Histamine H2 Antagonists
  • Hypoglycemic Agents
  • Octamer Transcription Factor-1
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 2
  • POU2F1 protein, human
  • SLC22A2 protein, human
  • SLC47A1 protein, human
  • SLC47A2 protein, human
  • Triazines
  • Cimetidine
  • imeglimin