Bioequivalence Assessment of the Fixed Dose Combination of Linagliptin/Metformin (2.5mg/850mg) Film Coated Tablets in Healthy Human Subjects: A Randomized, Open-Label, Two-Period Crossover Study
Abstract:
Type 2 diabetes mellitus (T2DM) is a
chronic, progressive disease with substantial global prevalence and
far-reaching health consequences. Combination oral anti-diabetic therapies
often provide greater glycemic control compared to monotherapy. Among these,
the fixed-dose combination (FDC) of linagliptin and metformin is widely used
due to complementary mechanisms of action that enhance glycemic management:
metformin acts predominantly via hepatic and peripheral insulin sensitization,
while linagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, amplifies
incretin activity to promote insulin secretion and inhibit glucagon release.
The present study investigates the bioequivalence of two formulations, each
containing 2.5mg linagliptin and 850mg metformin, under fasting conditions in
healthy Indian males. A single-center, open-label, randomized, two-period
crossover trial was conducted. The study enrolled 28 healthy male volunteers,
each receiving single doses of both the test and reference formulations with a 36-day
washout. Pharmacokinetic (PK) parameters (Cmax, AUC0–t,
AUC0–∞, Tmax, t1/2) were assessed using
validated LC-MS/MS. Bioequivalence was determined by the 90% confidence
intervals (CIs) for the geometric mean ratio (GMR) of ln-transformed Cmax
and AUC remaining within 80–125%. The results confirmed bioequivalence, as all
CIs fell within the regulatory limits. No significant adverse events were
observed, and both drugs were well tolerated, supporting their interchangeable
use in clinical practice in India.
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