occurred in the stomach regardless of water volume administered.
Mean time to complete tablet erosion was 85 minutes with 50 mL water and 57 minutes with 240 mL water.
Semaglutide plasma exposure, measured by the area under the concentration-time curve, was approximately 70% higher with 50 mL water compared to 240 mL water.
The maximum concentration of semaglutide was also higher with 50 mL water, reaching statistical significance.
The median time to maximum semaglutide concentration was consistent at 1.5 hours, regardless of water volume.
Longer times to complete tablet erosion and gastric emptying were significantly correlated with higher plasma semaglutide levels.
Simplified
Semaglutide, a glucagon-like peptide-1 (GLP-1) analogue, has been coformulated in a tablet with the absorption enhancer, sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). We investigated tablet erosion and the pharmacokinetics of oral semaglutide administered with 2 different water volumes and evaluated the relationships between these parameters. In a randomized, single-center (Quotient Sciences, UK), open-label, 2-period crossover trial, 26 healthy men received single doses of 10 mg oral semaglutide with 50 or 240 mL water while fasting. Tablet erosion and gastrointestinal transit were assessed by gamma scintigraphy. Semaglutide and SNAC plasma concentrations were measured until 24 and 6 hours, respectively, after administration. (CTE) occurred in the stomach irrespective of water volume administered with the tablet (primary end point). Mean time to CTE was 85 versus 57 minutes with 50 versus 240 mL water (ratio 50/240 mL, 1.51; 95% confidence interval, 0.96-2.37; P = .072). Area under the semaglutide concentration-time curve from 0 to 24 hours () and maximum semaglutide concentration (C) were ∼70% higher with 50 versus 240 mL water (P = .056 and P = .048, respectively). Median time to maximum semaglutide concentration (t) was 1.5 hours independent of water volume with dosing. Higher AUCand Cand longer twere significantly correlated with longer time to CTE and later gastric emptying of tablet and water (all P < .05). The safety profile was as expected for the GLP-1 receptor agonist drug class. In conclusion, the oral semaglutide tablet erodes in the stomach irrespective of water volume with dosing. Slower tablet erosion in the stomach results in higher semaglutide plasma exposure. 0-24h,semaglutide max,semaglutide max,semaglutide0-24h,semaglutide max,semaglutide max,semaglutide
Key numbers
1.51
Mean Time to Complete Erosion Increase
Mean time to was 85 minutes with 50 mL vs. 57 minutes with 240 mL.
70%
Higher Semaglutide Exposure
and maximum concentration were approximately 70% higher with 50 mL vs. 240 mL water.
24 of 26
Subjects Completed Trial
Out of 26 subjects exposed to trial product, 24 completed the trial.
Full Text
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Tine A. Bækdal, Morten Donsmark, and Flemming L. Søndergaard are employees and shareholders of Novo Nordisk A/S. Marie‐Louise Hartoft‐Nielsen was an employee of Novo Nordisk A/S at the time of conduct of the trial and preparation of this article and is a shareholder of Novo Nordisk A/S. Alyson Connor declares no conflicts of interest. Medical writing support was provided by Carsten Roepstorff, PhD, CR Pharma Consult, Copenhagen, Denmark and was funded by Novo Nordisk.
