• A new clinical trial in Italy investigates the efficacy of oral semaglutide.
  • Semaglutide  and other GLP-1 agonist drugs to treat diabetes, cardiovascular health,  and weight loss, are most widely available as injectable medications.
  • The  study finds that oral versions of the drug perform best in patients in  the early stages of diabetes, and not as well as injectables for other  people.
  • Even though doses of oral semaglutide  are significantly larger than injectable medications, far less of it  gets into the blood stream, potentially reducing its effectiveness.
  • Semaglutide,  the active ingredient in diabetes drugs that have also become popular  as a weight-loss aid, is primarily available in injectable form.
  • This includes the two most widely used drugs, Wegovy and Ozempic. Rybelsus is currently the only oral semaglutide drug on the market.
  • In  a new Italian study conducted in a clinical setting, oral semaglutide  was found to be most effective in people with a recent diagnosis of  diabetes, with “suboptimal” benefits for other diabetes patients.
  • The study’s results suggest that oral semaglutide may be of most use in the early stages of diabetes.
  • People whose diabetes was recently diagnosed showed significant improvements in levels of HbA1c — a measurement of blood sugar — and their body weight.
  • The study results appear in the Journal of Clinical Medicine.
  • Oral semaglutide most helpful in early stages of diabetes
  • Semaglutide  is a GLP-1 agonist that mimics the glucagon-like peptide-1 hormone. In  doing so, it stimulates the release of insulin by the pancreas. It also  slows the emptying of the stomach, providing a sense of fullness that  leads to less eating.
  • A significant effect of taking semaglutide  is weight loss. Excess body weight is a risk factor for both diabetes  and cardiovascular disease (CVD).
  • The study found an  improvement in glycemic — blood sugar — control in those patients in the  early stages of diabetes, along with a broad spectrum of beneficial  metabolic changes.
  • The researchers also observed positive changes related to cardiovascular risk. These included improved lipid profiles, eGFR — an indicator of kidney function — and blood pressure.
  • Of semaglutide drugs, only Wegovy is officially approvedTrusted Source by the Federal Food and Drug Administration (FDA) for weight loss.  However, other semaglutide drugs approved for treating diabetes and CVD,  such as Ozempic, are frequently used “off-label” for weight loss.
  • What previous research on oral semaglutide says
  • Oral  semaglutide has been the subject of several studies, with mixed  findings. A definitive assessment of its efficacy has yet to be  determined.
  • In the PIONEER-6 trial funded by Novo Nordisk — the manufacturer of Wegovy and Ozempic —  oral semaglutide performed better than a placebo, particularly at high  weekly doses of 14 milligrams (mg) that produced a 21% reduction in  cardiovascular risk.
  • A February 2024 study concluded that oral semaglutide may be most valuable as an add-on to the injectable form.
  • Sumera Ahmed, MD,  of the Metabolic Research Center, College of Osteopathic Medicine at  Touro University, CA, not involved in the current study, said that for  now: “We would still need to await the results of the SOUL studyTrusted Source which is a cardiovascular outcome trial for oral semaglutide to really  determine its benefit on reduction of MACE, or major adverse  cardiovascular events.”
  • Oral semaglutide may be a promising alternative
  • “Having semaglutide available as an oral or injectable allows accommodation for patient preferences,” said Vanita R. Aroda, MD,  who specializes in endocrinology, diabetes, and hypertension at Brigham  and Women’s Hospital in Boston. Aroda was also not involved in the new  study.
  • ”This flexibility may be especially important for  adolescents where there is a major need for safe pharmacology  treatments,” noted Andrew Hogan, PhD, who is an associate professor of immunology at Ireland’s Maynooth University, and also not involved in the study.
  • Ahmed  added that oral semaglutide may also offer reassurance for some current  semaglutide patients concerned about nationwide shortages of the  injectable drug.
  • Dosage makes a difference
  • The  typical dosing for Ozempic, said Ahmed, is weekly doses of 0.25 mg, 0.5  mg, 1 mg, and 2 mg, increased at four-week intervals based on the  presence and toleration of gastrointestinal side effects. For Wegovy, it  is 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg per week, increased in the  same manner.
  • The participants in the new study were given daily  oral prescriptions of 3 mg before being raised to 7 mg. Most of the  study cohort remained at a maximum of 7 mg daily for the study period.
  • For  about 2% of participants, the daily dose was increased to 14 mg. The  researchers reported that even the 14 mg dose was generally well  tolerated.
  • At 14 mg per day, the weekly dose adds up to 98 mg per week, far larger than the maximum Wegovy dose of 2.4 mg per week.
  • Aroda  explained why study participants were able to tolerate such a high dose  of the drug. “Keep in mind, the bioavailability of semaglutide — the  amount of semaglutide that actually is absorbed via the  [gastrointestinal] tract — is quite low,” she said.
  • “The levels of  semaglutide, in the blood achieved tend to be slightly less and more  variable than what is seen with injectable semaglutide doses that are  available,” she reported.
  • Hogan pointed out the high tolerability of oral semaglutide in another study, nothing that, “[i]n the OASIS trialsTrusted Source,  it was tested at 50 mg daily and the side effects seemed to be similar  to injections — mild to moderate nausea — which faded over time.”
  • Beyond patient preferences, injectable semaglutide is more effective than the oral version. Even so, said Hogan:

  • “Oral  delivery of semaglutide — and potentially future formulations — will  make these medications more accessible, allowing doctors to choose the  best route for their patient.”