Oral Semaglutide: The First-available Noninjectable Glucagon-like Peptide 1 Receptor Agonist
In many cases of T2DM, multiple therapies are required to achieve adequate glucose control. In patients with CVD, the use of glucagon-like peptide 1 receptor agonist (GLP-1RA) or a sodium-glucose cotransporter (SGLT)-2 inhibitor is recommended to reduce CVD risk. Author Jason Powell and two of his colleagues (2020) conducted a review entitled “Oral Semaglutide: The First-available Noninjectable Glucagon-like Peptide 1 Receptor Agonist”, published in and Elsevier journal to observe if oral semaglutide has a similar effect as the injectable medications of the same class. Below is the summary of the review.
Objective:
To review the safety of the medication, recommended dose, and costs of oral semaglutide for managing T2DM.
Method:
Literature, with the word semaglutide, was sourced from data published from January 2017. Phase II trials of pharmacokinetics and Phase III trials of PIONEER studies approved by the US FDA were selected.
Findings:
The bioavailability of oral peptide-based drugs is limited due to gastric acidity and proteolytic enzymes. The bioavailability of oral semaglutide was improved by co-formulating it with salcaprozate sodium (SNAC). The results of Phase II trials demonstrated that the concentration of a single dose of 2 – 20mg semaglutide was found highest when it was co-formulating it with 300mg of SNAC. Simultaneously, during the multiple-dose trial of semaglutide, the ingestion of 60mg of semaglutide resulted in too many adverse drug reactions. The various doses that were tested were 20, 40, and 60mg. However, researchers of the Phase II trial found a significant reduction in HbA1c and weight with oral semaglutide.
The Phase III PIONEER trial series showed the ingestion of oral semaglutide showed a reduction in HbA1c and weight loss when compared with empagliflozin and sitagliptin. However, a non-inferior reduction of HbA1c and more adverse drug reactions were seen in comparison to liraglutide.
The renal safety profile of oral semaglutide was similar to other medications in the class of GLP-1RA. Oral semaglutide didn’t show superiority in preventing CV outcomes over other medications in the class of GLP-1RA. The authors noticed the insufficiency of data in regards to the tolerability of oral semaglutide in pregnant or breast-feeding patients. No studies are published regarding the use of oral semaglutide in pediatric populations. The medication is contraindicated in medullary thyroid carcinoma, multiple endocrine neoplasia syndrome type-2, or known hypersensitivity to semaglutide or any of its components. Authors have reported severe adverse events such as abdominal pain, vomiting, delaying effect on gastric emptying, pancreatitis, worsening of diabetic retinopathy as well as chronic kidney disease. The use of other drugs may decrease the absorption of oral semaglutide. The authors have advised ingesting semaglutide at least 30 min before food, beverages, or other medications.
After reviewing the literature authors concluded that the action of oral semaglutide was similar to the injectable medication in its similar class.
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