Lexaria Bioscience Corp. (NASDAQ:LEXX) has announced promising partial results from its GLP-1-H24-3 study, evaluating an oral formulation of DehydraTECH-processed tirzepatide against conventional injected Zepbound. The study, designed to assess tolerability and glycemic control, revealed a significant reduction in adverse events with the oral formulation while maintaining comparable efficacy in blood glucose reduction and insulin secretion.
The GLP-1-H24-3 study compared an oral version of DehydraTECH-processed Zepbound to conventional injected Zepbound. The injected Zepbound produced a total of 38 adverse events across the study group of 9 persons, whereas the oral DehydraTECH-tirzepatide only produced 20 adverse events, a reduction of 47%. Likewise, the injected Zepbound resulted in 22 gastrointestinal-related adverse events, whereas the oral DehydraTECH-tirzepatide resulted in only 10 GI-related adverse events, a reduction of 54%.
Tolerability and Glycemic Control
The data indicated that oral DehydraTECH-tirzepatide resulted in 47% fewer adverse events compared to the injectable version. Notably, gastrointestinal side effects, a common issue with GLP-1/GIP drugs, were reduced by 54% with the oral formulation. Richard Christopher, CEO of Lexaria, stated, "Lexaria is delighted, in our first-ever attempt to render a competitive version of an orally deliverable tirzepatide formulation, to have already achieved approximate parity in effectiveness with apparent superiority in tolerability to the advanced commercial, injected version of Zepbound already on the market."
Blood Glucose and Insulin Levels
The study also demonstrated that oral DehydraTECH-tirzepatide achieved a comparable overall reduction in blood glucose from baseline to the end of the 8-day observation period (p<0.05). The mean baseline blood glucose levels were 88.2+/-9.0 mg/dL for oral DehydraTECH-tirzepatide and 87.8+/-11.3 mg/dL for injected Zepbound, compared to the Study-ending levels of 83.2+/-5.7 mg/dL and 81.7+/-4.0 mg/dL respectively. Both formulations also produced similarly increased levels of insulin from baseline to the end of the study, although statistical significance (p<0.05) was only achieved in the injected Zepbound group. At peak times, the oral DehydraTECH-tirzepatide-induced insulin levels were approximately 100% higher than those from the Zepbound injection.
Study Design and Future Plans
The GLP-1-H24-3 study involved nine healthy subjects in a randomized, cross-over design. Participants received either 20 mg of oral DehydraTECH-tirzepatide daily for seven days or a single 2.5 mg injection of Zepbound. Lexaria intends to add a fifth study arm to its ongoing 12-week human study in Australia (GLP-1-H24-4), using DehydraTECH-tirzepatide in an oral capsule. This arm will initially use the same dose as the current study but will escalate to a dose roughly twice as high to further investigate blood sugar control and weight loss.
Implications for Oral GLP-1 Therapies
Currently, tirzepatide is only available in injectable form (Zepbound and Mounjaro). Lexaria's research suggests that an effective oral version with fewer adverse events could be highly valuable. While oral delivery typically requires higher API quantities due to lower bioavailability, Lexaria's DehydraTECH technology aims to improve oral delivery. In this study, the oral dose was 56 times higher than the injected dose; Lexaria believes further optimization could enhance performance.
