Are there oral natural Glucagon-like peptide-1 (GLP-1) options?

From the Guidelines

Yes, there are oral natural GLP-1 options available, with Semaglutide being the only FDA-approved oral GLP-1 receptor agonist medication, as noted in the 2023 study published in JAMA 1.

Key Points

• Semaglutide, brand name Rybelsus, comes in tablet form with dosages of 3 mg, 7 mg, and 14 mg, typically starting at the lowest dose and gradually increasing.
• Rybelsus must be taken on an empty stomach with no more than 4 ounces of plain water, at least 30 minutes before the first food, beverage, or other oral medications of the day, as this timing is crucial for the absorption enhancer to help the GLP-1 molecule survive the harsh stomach environment and enter the bloodstream.
• Oral semaglutide works by mimicking the incretin hormone GLP-1, which stimulates insulin secretion, suppresses glucagon release, slows gastric emptying, and reduces appetite, helping to lower blood glucose levels and potentially assist with weight loss, as supported by the findings in the STEP trials 1.
• While convenient as an oral option, its absorption can be more variable than injectable GLP-1 medications, and it may cause similar side effects including nausea, vomiting, diarrhea, and abdominal pain, especially during dose escalation, as reported in the 2020 study published in Diabetes Care 1.

Considerations

• The efficacy of semaglutide in weight loss has been demonstrated in clinical trials, with mean weight loss at 68 weeks being 14.9% and 16.0% in the STEP 1 and STEP 3 trials, respectively, compared to 2.4% and 5.7% for placebo 1.
• Long-term use of semaglutide is necessary to maintain weight loss, as significant weight regain was observed after cessation of treatment in the STEP trials 1.
• The SELECT study showed that semaglutide reduced the risk of cardiovascular events in adults with overweight or obesity without diabetes, with a hazard ratio of 0.80 (95% CI, 0.72-0.90) 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Oral Natural GLP1 Options

• There are currently no natural oral GLP1 options available, as most GLP-1 receptor agonists (GLP-1 RAs) are administered via subcutaneous injection 2, 3.
• However, a daily oral preparation of semaglutide has been recently approved, which has demonstrated clinical effectiveness close to the once-weekly subcutaneous preparation 2.
• The oral semaglutide has shown promising results in clinical trials, but it is not a natural product 3, 4.
• The current GLP-1 RAs available are exenatide, liraglutide, albiglutide, dulaglutide, lixisenatide, and semaglutide, all of which are synthetic peptides 3, 4.

Mechanism of Action

• GLP-1 RAs work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 2, 3.
• They have been shown to be effective in reducing HbA1c levels, body weight, and cardiovascular risk in patients with type 2 diabetes 2, 5, 6.

Safety and Efficacy

• GLP-1 RAs have been associated with a reduced risk of cardiometabolic disorders, infectious illnesses, and several respiratory conditions, but an increased risk of gastrointestinal disorders, hypotension, and arthritic disorders 5.
• The safety and efficacy of GLP-1 RAs have been extensively studied, and they are generally well-tolerated, but more research is needed to address concerns about pancreatitis and cancer 6.