Hence, interindividual variation in GLP-1R responsivity or route of administration are not major determinants of GLP-1RA effectiveness in the clinic. Increased body weight is the most important variable associated with reduced semaglutide exposure for both formulations. At typical exposure levels for oral semaglutide, the estimated response is 1.58% (oral) versus −1.62% (subcutaneous) for HbA 1c and 3.77% (oral) versus 3.48% (subcutaneous) reduction in body weight relative to baseline after 6 months. The dataset for external validation was obtained from a randomized, double-blind, placebo-controlled, doseresponse study evaluating the efficacy and safety of paliperidone palmitate at doses of 50, 100 and 150 mg equivalent. Each treatment was followed by a 1- to 3-week washout period. Subjects were released from the clinic 24 h after the start of dosing. We demonstrate that nearly identical exposure-response pharmacodynamic relationships are determined by plasma semaglutide levels achieved through oral versus injectable administration for changes in HbA 1c, body weight, biomarkers of cardiovascular risk, and AEs such as nausea and vomiting. Subjects were admitted to the unit on the morning of each dosing after overnight fasting and an oesophageal tube and intravenous lines were placed prior to dosing.
Whether clinically important responses and adverse events (AEs) are dependent on the route of administration has not been determined. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are used for the treatment of type 2 diabetes.
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