A new clinical trial in Italy is investigating the efficacy of oral semaglutide, a drug commonly used to treat diabetes, cardiovascular health, and aid in weight loss. Typically, semaglutide and other GLP-1 agonist drugs are available as injectable medications, with oral versions being a relatively new option. The study found that oral semaglutide performed best in patients in the early stages of diabetes, with less effectiveness in others. Despite larger doses of oral semaglutide, less of it gets into the bloodstream compared to injectables, potentially reducing its benefits. Semaglutide is primarily available in injectable form, including popular drugs such as Wegovy and Ozempic, with Rybelsus being the only oral option currently on the market.
The Italian study observed that oral semaglutide was most effective in individuals recently diagnosed with diabetes, resulting in significant improvements in blood sugar levels (HbA1c) and body weight. Semaglutide is a GLP-1 agonist that mimics the glucagon-like peptide-1 hormone, stimulating insulin release and slowing stomach emptying to provide a sense of fullness. Weight loss is a significant effect of semaglutide, and the study also found positive metabolic changes in addition to benefits related to cardiovascular risk factors such as improved lipid profiles, kidney function, and blood pressure. While only Wegovy is officially approved by the FDA for weight loss, other semaglutide drugs like Ozempic are commonly used off-label for this purpose.
Various studies on oral semaglutide have yielded mixed results, with its overall efficacy yet to be definitively established. One study funded by Novo Nordisk, the manufacturer of Wegovy and Ozempic, found that high weekly doses of oral semaglutide were more effective than a placebo, reducing cardiovascular risk by 21%. Oral semaglutide may be most beneficial as an add-on to injectable forms, as indicated by a February 2024 study. The SOUL study, a cardiovascular outcome trial for oral semaglutide, is expected to provide more information on its potential benefits. Having both oral and injectable options for semaglutide allows for patient preferences and addresses concerns about injectable drug shortages.
The flexibility of oral semaglutide may be particularly important for patients with preferences for oral medication or adolescents in need of safe pharmacological treatments. Participants in the Italian study were prescribed daily doses of oral semaglutide, starting at 3 mg and increasing to 7 mg, with a small percentage receiving a daily dose of 14 mg. Despite the relatively larger dosing of oral semaglutide compared to injectables, it was generally well tolerated. While the bioavailability of oral semaglutide is lower than that of injectables, resulting in slightly lower and more variable blood levels, the drug was found to be well tolerated by participants in other studies, with side effects such as nausea fading over time.
Despite the efficacy of injectable semaglutide being greater than the oral version, the availability of oral formulations provides more accessibility and options for patients and healthcare providers. The potential for future formulations of oral semaglutide may further enhance the utilization of these medications. Overall, the study results suggest that oral semaglutide may be most beneficial for individuals in the early stages of diabetes, indicating promising potential for this form of the drug in managing the condition and associated risks. Continued research and clinical trials are needed to further establish the effectiveness and safety of oral semaglutide for a wider range of patients and health conditions.
