Bioequivalence Assessment of Sitagliptin/Metformin Extended-Release Fixed-Dose Combinations in Healthy Mexican Subjects Under Fasting and Fed Conditions

Background/Objectives: Management of Type 2 Diabetes (T2D) frequently requires combination therapy. Fixed-dose combinations (FDCs) of sitagliptin and extended-release (ER) metformin improve therapeutic adherence but pose biopharmaceutical challenges related to matrix robustness and food–drug interactions. This study evaluated the pharmacokinetics and bioequivalence of two generic sitagliptin/metformin ER FDCs (50/1000 mg and 100/1000 mg) versus reference products under fasting and fed conditions in healthy Mexican subjects. Methods: Four independent, randomized, open-label, two-period, single-dose crossover studies were conducted. We enrolled 184 healthy subjects (46 per study) with a 7-day washout period. Plasma concentrations of sitagliptin and metformin were quantified using a validated LC-MS/MS method. Results: The 90% confidence intervals for the geometric mean ratios (Test/Reference) of Cmax, AUC0–t, and AUC0-∞ for both analytes fell entirely within the 80.00–125.00% bioequivalence acceptance range across all studies. Under fed conditions, prolonged tmax and the absence of concentration spikes confirmed ER matrix preservation, with no evidence of food-induced dose dumping. The safety profile was highly favorable; all adverse events were mild or moderate and completely resolved without sequelae. Conclusions: The evaluated generic sitagliptin/metformin ER FDCs demonstrated pharmacokinetic bioequivalence to the reference products under fasting and fed conditions. These findings meet stringent regulatory requirements (NOM-177-SSA1-2013), support pharmacokinetic bioequivalence as the regulatory basis for safe therapeutic interchangeability, and provide robust, region-specific clinical data for the Latin American population. ClinicalTrials.gov identifiers: NCT07763899, NCT07763912, NCT07763951, and NCT07763964.