A pharmacokinetic and pharmacodynamic drug-drug interaction study of dorzagliatin and empagliflozin in patients with type 2 diabetes and obesity: an open-label phase I trial
Abstract
Combination therapy of glucokinase activators and sodium-glucose cotransporter-2 inhibitors may exhibit potent glucose-lowering effects and improvement of β-cell function and insulin sensitivity in patients with type 2 diabetes mellitus, given their complementary mechanisms of action. However, the safety, pharmacokinetic interactions and pharmacodynamic effects of such combinations remain unexplored. To address this gap, we conduct an open-label, sequential phase I trial (ClinicalTrials.gov, NCT03790787 ) evaluating the dorzagliatin and the sodium-glucose cotransporter-2 inhibitor empagliflozin in patients with type 2 diabetes mellitus and obesity in the US. After strict screening against the inclusion/exclusion criteria, 16 participants are deemed eligible. Participants receive sequential treatments-empagliflozin alone, empagliflozin plus dorzagliatin, and dorzagliatin alone-five days for each regimen, followed by a comprehensive assessment of pharmacokinetic profiles and safety. The primary outcomes included GMR for Cmax and AUC0-24h of empagliflozin and dorzagliatin of pharmacokinetic parameters and the incidence of adverse events, abnormal vital signs, abnormal clinical laboratory findings, and 12-lead electrocardiogram abnormalities of safety profile. A total of 27 adverse events occurs in 9 participants (56.3%), the majority of which are mild, with the exception of one case of moderate constipation. No clinically significant findings or changes attributable to study…
How strong is the evidence?
Evidence Hub reads this as a clinical trial, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 16 participants or records.
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