Summary: In this Phase 1 crossover study of healthy Korean volunteers, a fixed-dose combination (FDC) of enavogliflozin 0.3 mg and gemigliptin 50 mg was pharmacokinetically equivalent to the two drugs taken as separate tablets, with comparable half-lives (enavogliflozin approximately 12.2 to 12.6 hours; gemigliptin approximately 18 hours) and similar safety. A high-fat meal delayed enavogliflozin peak concentration (median Tmax 1.25 to 2.00 hours) but did not change systemic exposure. This is a bioequivalence and food-effect study in healthy subjects, not a test of glycaemic efficacy.
PICO Summary
| Element | Detail |
|---|---|
| Population | Healthy adult volunteers (age 19 years or older, weight 50 kg or more, BMI 18.0 to 30.0 kg/m2) in South Korea. Two randomised crossover studies: Study I (separate versus FDC, 8-day washout) and Study II (open-label food effect, 7-day washout). |
| Intervention | Single oral dose of the enavogliflozin 0.3 mg / gemigliptin 50 mg fixed-dose combination (Study I); and enavogliflozin 0.3 mg taken after a high-fat meal, in the fed state (Study II). |
| Comparison | Single oral dose of enavogliflozin 0.3 mg plus gemigliptin 50 mg as separate tablets (Study I); and enavogliflozin 0.3 mg taken in the fasted state (Study II). |
| Outcome | The FDC was reported as pharmacokinetically equivalent to the separate tablets. Enavogliflozin median Tmax was 1.25 hours in both groups; mean half-life was 12.56 plus or minus 4.04 hours (separate) versus 12.23 plus or minus 3.46 hours (FDC). Gemigliptin Tmax was 2.00 hours (separate) versus 3.00 hours (FDC); half-life was 18.04 plus or minus 1.75 hours versus 18.67 plus or minus 2.54 hours. A high-fat meal delayed enavogliflozin median Tmax (1.25 to 2.00 hours) without affecting systemic exposure (half-life 12.49 plus or minus 2.12 hours fasted versus 12.30 plus or minus 2.81 hours fed). Safety was comparable across conditions, with no serious adverse events reported. Formal 90% confidence intervals for the bioequivalence ratios were not given in the abstract. |
Expert Commentary
This is a clean, well-designed Phase 1 bioequivalence and food-effect study, and the verdict is that it does what it sets out to do: the fixed-dose combination behaves pharmacokinetically like the two separate tablets, and enavogliflozin can be taken with or without food. The convergent half-lives and overlapping exposure parameters across formulations are reassuring, and a single co-formulated tablet is a sensible step that may support adherence once both agents are already indicated. The central caveat is what this study deliberately does not address: conducted in a small number of healthy volunteers after single doses, it tests pharmacokinetics and tolerability, not glycaemic efficacy, durability, or safety in people with type 2 diabetes, who differ in renal function, comedication, and metabolic state. The abstract also reports no formal 90% confidence intervals for the bioequivalence ratios, so the strength of the equivalence claim cannot be fully judged from the summary alone. Two authors are affiliated with the manufacturer, Daewoong Pharmaceutical, and Study II was open-label, both of which warrant the usual circumspection. Can I use this with my patients? Not yet as a treatment decision; this is a formulation and food-effect study, so its practical value is the regulatory and convenience case for a combined pill rather than evidence of clinical benefit. I would like to see the full confidence intervals and efficacy data in patients before drawing therapeutic conclusions.
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
