Pharmacokinetics and Safety of Fixed‐Dose Versus Separate Enavogliflozin/Gemigliptin Combinations, and Food Effect on Enavogliflozin in Healthy Korean Subjects

Envlo (enavogliflozin) 0.3 mg, an SGLT2 inhibitor, was approved in Korea in 2022 for glycemic control in type 2 diabetes (T2DM). This study evaluates its safety, pharmacokinetics, and food effects. Healthy subjects (age ≥ 19, weight ≥ 50.0 kg, body mass index (BMI) 18.0–30.0 kg/m 2 ) were enrolled. Study I was a randomized, two‐way crossover study with an 8‐day washout, where subjects received either a separate or a fixed‐dose combination (FDC) of enavogliflozin 0.3 mg/gemigliptin 50 mg. Study II, a randomized, open‐label, two‐way crossover design with a 7‐day washout, compared the food effect of a single dose of enavogliflozin in fed versus fasted after a high‐fat meal. In study I, enavogliflozin reached peak plasma concentration at 1.25 h (median) in both groups. The mean half‐life ( t 1/2 ) was also comparable, recorded as 12.56 ± 4.04 h for the separate combination and 12.23 ± 3.46 h for the FDC. Gemigliptin peaked at 2.00 h in the separate combination and at 3.00 h in the FDC. The mean t 1/2 was 18.04 ± 1.75 h for the separate combination and 18.67 ± 2.54 h for the FDC. In study II, the plasma concentration of enavogliflozin 0.3 mg peaked at 1.25 and 2.00 h (median), indicating a delayed T max in the fed group. The average t 1/2 was similar at 12.49 ± 2.12 h and 12.30 ± 2.81 h, respectively. The FDC of enavogliflozin and gemigliptin demonstrated pharmacokinetic equivalence and comparable safety to their co‐administration as separate agents. Furthermore, the systemic exposure of enavogliflozin was not affected by food intake, supporting its potential for flexible, meal‐independent use in clinical settings.