{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:59:12Z","timestamp":1785495552063,"version":"3.56.0"},"reference-count":52,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T00:00:00Z","timestamp":1785456000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Asofarma de M\u00e9xico S.A. de C.V."}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Fixed-dose combinations (FDCs) improve therapeutic adherence in type 2 diabetes. These studies aimed to evaluate the pharmacokinetics and establish the bioequivalence of four immediate-release empagliflozin\/metformin FDC formulations under fed conditions in healthy Mexican subjects. Methods: A total of 42 healthy volunteers per study (168 total) were enrolled in four randomized, open-label, two-way crossover, single-dose studies with a 14-day washout period. Formulations were administered orally under standardized fed conditions. Plasma concentrations of both drugs were quantified using a validated liquid chromatography coupled with tandem mass spectrometry (LC-MS\/MS) method. Results: Across all dose strengths, the 90% confidence intervals (CIs) for the geometric mean ratios of peak plasma concentration (Cmax) and area under the concentration\u2013time curve (AUC0-t) for both empagliflozin and metformin were entirely within the 80.00\u2013125.00% bioequivalence acceptance range. The specific 90% CIs for Cmax and AUC0-t were: Study A (5\/850 mg): empagliflozin (90.18\u2013103.16%; 94.37\u2013101.81%), metformin (98.43\u2013107.69%; 97.18\u2013106.62%); Study B (12.5\/500 mg): empagliflozin (91.94\u2013102.77%; 93.38\u201398.51%), metformin (92.58\u2013101.73%; 94.85\u2013103.91%); Study C (12.5\/850 mg): empagliflozin (95.47\u2013107.74%; 95.34\u2013101.25%), metformin (94.19\u2013103.59%; 94.06\u2013103.21%); and Study D (12.5\/1000 mg): empagliflozin (94.53\u2013107.10%; 98.13\u2013105.66%), metformin (98.89\u2013107.51%; 99.25\u2013109.92%). Regarding safety, no serious adverse events occurred, and all reported events were mild or moderate and resolved completely. Conclusions: All evaluated empagliflozin\/metformin FDCs successfully demonstrated bioequivalence and a favorable safety profile under fed conditions. These findings fulfill regulatory requirements and support their therapeutic interchangeability in clinical practice. An exploratory power-model analysis indicated a modest trend toward less-than-dose-proportional metformin exposure across the 500\u20131000 mg range (slope \u03b2 \u2248 0.77\u20130.78). NCT07633015, NCT07633054, NCT07633028, and NCT07633041.<\/jats:p>","DOI":"10.3390\/ph19081200","type":"journal-article","created":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:11:38Z","timestamp":1785492698000},"page":"1200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bioequivalence Evaluation of Immediate-Release Empagliflozin\/Metformin Fixed-Dose Combination Tablets Under Fed Conditions in Healthy Mexican Subjects and Exploratory Analysis of Metformin Dose Proportionality"],"prefix":"10.3390","volume":"19","author":[{"given":"Erika Gabriela","family":"Guido \u00c1vila","sequence":"first","affiliation":[{"name":"Asofarma de M\u00e9xico S.A. de C.V., Av. Santa Fe 485, Lomas de Santa Fe, Contadero, Cuajimalpa de Morelos, Ciudad de M\u00e9xico 05348, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Mart\u00ednez Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"FS Scientia Pharma S.A. de C.V (Authorized Third Party), Av. Himno Nacional 1330, Jard\u00edn, San Luis Potos\u00ed 78270, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Porfirio","family":"de la Cruz Cruz","sequence":"additional","affiliation":[{"name":"Doctorado Institucional en Ingenier\u00eda y Ciencia de Materiales (DICIM) de la Universidad Aut\u00f3noma de San Luis Potos\u00ed (UASLP), Av. Sierra Leona No. 550, Col. Lomas 2da. Secci\u00f3n, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar Emmanuel","family":"Hern\u00e1ndez Pi\u00f1a","sequence":"additional","affiliation":[{"name":"Asofarma de M\u00e9xico S.A. de C.V., Av. Santa Fe 485, Lomas de Santa Fe, Contadero, Cuajimalpa de Morelos, Ciudad de M\u00e9xico 05348, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0642-0033","authenticated-orcid":false,"given":"Jos\u00e9 Trinidad","family":"P\u00e9rez-Urizar","sequence":"additional","affiliation":[{"name":"FS Scientia Pharma S.A. de C.V (Authorized Third Party), Av. Himno Nacional 1330, Jard\u00edn, San Luis Potos\u00ed 78270, Mexico"},{"name":"Facultad de Ciencias Qu\u00edmicas de la Universidad Aut\u00f3noma de San Luis Potos\u00ed, Av. Dr. Nava No. 6, Zona Universitaria, San Luis Potos\u00ed 78210, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4676-1625","authenticated-orcid":false,"given":"Abraham","family":"Escobedo-Moratilla","sequence":"additional","affiliation":[{"name":"Asofarma de M\u00e9xico S.A. de C.V., Av. Santa Fe 485, Lomas de Santa Fe, Contadero, Cuajimalpa de Morelos, Ciudad de M\u00e9xico 05348, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,31]]},"reference":[{"key":"ref_1","first-page":"530","article-title":"Cascadas de tamizaje y atenci\u00f3n de la diabetes tipo 2 en M\u00e9xico","volume":"66","author":"Stern","year":"2024","journal-title":"Salud Publica Mex."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"American Diabetes Association Professional Practice Committee (2025). 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2025. 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