Summary: In healthy Korean volunteers, a fixed-dose combination tablet of enavogliflozin 0.3 mg and gemigliptin 50 mg was shown to be pharmacokinetically equivalent and comparably tolerated relative to the two drugs taken as separate tablets. Enavogliflozin half-life was approximately 12.2 to 12.6 hours and gemigliptin approximately 18 hours across both formulations, and a high-fat meal delayed enavogliflozin time-to-peak (1.25 to 2.00 hours) without reducing systemic exposure.
PICO Summary
| Element | Detail |
|---|---|
| Population | Healthy adult volunteers (age ≥ 19 years, BMI 18.0 to 30.0 kg/m², weight ≥ 50.0 kg), Republic of Korea; two randomized two-way crossover studies (Study I: 8-day washout; Study II: open-label, 7-day washout). |
| Intervention | Fixed-dose combination tablet of enavogliflozin 0.3 mg plus gemigliptin 50 mg (Study I); single-dose enavogliflozin 0.3 mg given after a high-fat meal, i.e. fed condition (Study II). |
| Comparison | Separate co-administration of enavogliflozin 0.3 mg and gemigliptin 50 mg tablets (Study I); the same single dose given fasted (Study II). |
| Outcome | Study I: pharmacokinetic equivalence with comparable safety. Enavogliflozin median Tmax 1.25 h in both arms; mean t½ 12.56 ± 4.04 h (separate) versus 12.23 ± 3.46 h (FDC). Gemigliptin median Tmax 2.00 h (separate) versus 3.00 h (FDC); mean t½ 18.04 ± 1.75 h versus 18.67 ± 2.54 h. Study II: high-fat meal delayed enavogliflozin median Tmax from 1.25 to 2.00 h, with similar t½ (12.49 ± 2.12 h fed versus 12.30 ± 2.81 h fasted) and systemic exposure unaffected by food. Formal 90% confidence intervals for exposure ratios were reported in the source; no ARR/NNT applies to this pharmacokinetic design. |
Expert Commentary
This is a phase-1 bioequivalence and food-effect programme in healthy volunteers, and it should be read as such: the work establishes that the fixed-dose combination delivers enavogliflozin and gemigliptin with pharmacokinetics that are interchangeable with the separate tablets, and that a high-fat meal delays the time to peak without curtailing overall enavogliflozin exposure. No glycaemic or clinical outcomes were measured, so nothing here speaks to efficacy in diabetes; the contribution is regulatory and practical rather than therapeutic. The headline verdict is that pharmacokinetic equivalence was met and tolerability was comparable, with only mild adverse events consistent with the SGLT2-inhibitor and DPP-4-inhibitor classes. The principal limitation is generalisability: a small, healthy, single-ethnicity sample with short washout periods cannot be assumed to predict steady-state behaviour, drug interactions, or tolerability in older patients with type 2 diabetes, renal impairment, or polypharmacy. Industry sponsorship is also material, since the manufacturer of enavogliflozin funded the study and contributed co-authors, and the open-label food-effect design adds a further caveat. Can I use this with my patients? Not yet as a clinical decision, but for an adult already stable on both agents separately, these data support that switching to the co-formulated tablet, taken with or without food, should not change drug exposure. Confirmatory efficacy and real-world tolerability data in people with diabetes would be welcome before broader reliance.
References
Choi YS, Na J, Park SY, Cho JM, Jeong Y, Hwang JG. Pharmacokinetics and safety of fixed-dose versus separate enavogliflozin/gemigliptin combinations, and food effect on enavogliflozin in healthy Korean subjects. Clin Transl Sci. 2025;18(10):e70376. doi:10.1111/cts.70376
