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

Abstract

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/m²) 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.