Study Finds No Significant PK Effect of Coadministering Evogliptin With Empagliflozin or Dapagliflozin


Among a small cohort of healthy Korean male volunteers, evogliptin combined with empagliflozin or dapagliflozin had no significant effects on the pharmacokinetics (PK) of each drug.

In healthy male volunteers without diabetes, administration of evogliptin in combination with either empagliflozin or dapagliflozin had no significant effect on the pharmacokinetics (PK) of each drug, according to a study published in Clinical and Translational Science.

Evogliptin is a novel dipeptidyl peptidase-4 inhibitor (DPP4i) for managing glycemic control in patients with type 2 diabetes (T2D). The study focused on evaluating the PK and pharmacodynamic (PD) interactions between evogliptin and the 2 sodium glucose cotransporter-2 inhibitors (SGLT2i), as combining these therapies has been shown as an effective treatment option for T2D.

The randomized, open-label study involved multiple doses, 3 treatments, and 2 treatment sequences per study arm in healthy Korean volunteers. Volunteers were aged between 19 and 55 years and weighed more than 55 kg—about 121 pounds—with body mass index (BMI) ranging between 18.5 and 25 kg/m2 at screening.

In the first study arm, 18 participants received 5 mg of evogliptin once daily for 7 days (EV), 25 mg of empagliflozin once daily for 5 days (EP), and the combination of both drugs once daily for 5 days (EV+EP).

In the second study arm, 18 other participants also received 5 mg of evogliptin once daily for 7 days, but instead received 10 mg of dapagliflozin once daily for 5 days (DP), and the combination of both drugs once daily for 5 days (EV+DP).

Participants received the treatments in 1 of 4 possible sequences overall:

  • EV, EV+EP, and EP
  • EP, EV, and EV+EP
  • EV, EV+DP, and DP
  • DP, EV, and EV+DP

Researchers collected serial blood samples to evaluate any PK changes and performed oral glucose tolerance tests to look for any PD changes.

“The PD parameters were the area under the time-effect curve at a steady state of serum glucose (AUECglu), the change in AUEC of blood glucose from baseline (ΔAUECglu), area under the time-effect curve at a steady state of plasma insulin (AUECins), the change in AUEC of blood insulin from baseline (ΔAUECins), and urinary glucose excretion (UGE) over 24 hours,” the authors explained.

The study showed that co-administration of evogliptin with either empagliflozin or dapagliflozin did not significantly alter the geometric mean ratio or CI of the main PK parameters: Cmax,ss and AUCτ,ss.

Additionally, neither combination treatment resulted in significant PD changes—reflected by the glucose-lowering effect—nor had a significant effect on the PK profiles of each drug.

The AUECglu showed a statistically significant difference compared with baseline AUEC levels across the board, with the exception of DP. For the EV+EP combination treatment, the researchers found that the ΔAUECglu was lower by only 4.1% and 10.3% compared with that of EV and EP alone, respectively (P > 0.05). Similarly, the AUECΔglu for the EV+DP combination was only 1.2% and 10.2% lower than that of EV and DP alone, respectively (P > 0.05).

The researchers did not find any statistically significant differences in ΔAUECins across the cohort, nor in 24-hour UGE between the EV+EP combination treatment and EP/EV+DP and DP. While adverse events were recorded, all were drug-related and deemed mild, as most participants recovered without additional treatment.

“As co-administration of evogliptin and SGLT2i did not show PK interactions, it is unlikely that these drugs used in combination would raise the possibility of increased toxicities or diminished effects through PK-based alterations in exposure,” the authors said. In addition, co-administration of evogliptin and dapagliflozin has shown additive PD effect and safety profiles in T2DM patients. Therefore, combination therapy of evogliptin and empagliflozin or dapagliflozin would be an effective and safe treatment option, which can facilitate therapy of patients with T2DM.”


Kim D, Choi M, Jin BH, et al. Pharmacokinetic and pharmacodynamic drug-drug interactions between evogliptin and empagliflozin or dapagliflozin in healthy male volunteers. Clin Transl Sci. Published online June 6, 2023. doi:10.1111/cts.13566

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