Imeglimin Does Not Induce Clinically Relevant Pharmacokinetic Interactions When Combined with Either Metformin or Sitagliptin in Healthy Subjects

Clin Pharmacokinet. 2020 Oct;59(10):1261-1271. doi: 10.1007/s40262-020-00886-y.


Background and objectives: Imeglimin (IMEG) is the first in a novel class of oral glucose-lowering agents with a unique mechanism of action targeting mitochondrial bioenergetics. We assessed whether repeated co-administration of IMEG and either metformin (MET) or sitagliptin (SITA) would influence the pharmacokinetics of either MET or SITA in healthy Caucasian men.

Methods: Healthy Caucasian men received either MET 850 mg twice daily with placebo (n = 16) or SITA 100 mg once daily with placebo (n = 16) on days 1-6, followed by MET 850 mg twice daily with IMEG 1500 mg twice daily or SITA 100 mg once daily with IMEG 1500 mg twice daily on days 7-12. Pharmacokinetic parameters were determined from blood and urine; levels of all compounds were evaluated using liquid chromatography with tandem mass spectrometry.

Results: Systemic exposure (AUC0-τ area under the plasma concentration-time curve over a dosing interval and maximum concentration) to MET was 14% and 10% lower, respectively, when administered with IMEG. Approximately 40% of MET was excreted unchanged in urine, decreasing to 34% when given with IMEG. The 90% confidence intervals for AUC0-τ and maximum concentration indicated no effect of co-administration on systemic exposure to MET. Mean AUC0-τ and maximum concentration of SITA were similar with or without IMEG. Median times to maximum concentration were 0.7 and 1.0 h and mean elimination half-lives were 8.2 and 8.7 h with and without IMEG, respectively. Systemic exposure to IMEG was similar to previous phase I studies.

Conclusions: Co-administration of IMEG with MET or SITA did not result in clinically relevant changes in systemic exposure to MET or SITA, although minor reductions in exposure (AUC0-τ and maximum concentration) and renal elimination were noted when MET was given with IMEG vs placebo.

Clinical trial registration: EudraCT2009-014520-40 (MET-IMEG DDI) and EudraCT2010-022926-34 (SITA-IMEG DDI).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Area Under Curve
  • Healthy Volunteers
  • Humans
  • Hypoglycemic Agents / pharmacokinetics*
  • Male
  • Metformin* / pharmacokinetics
  • Sitagliptin Phosphate* / pharmacokinetics
  • Triazines / pharmacokinetics*


  • Hypoglycemic Agents
  • Triazines
  • Metformin
  • Sitagliptin Phosphate
  • imeglimin

Associated data

  • EudraCT/EudraCT2009-014520-40
  • EudraCT/EudraCT2010-022926-34