From the Guidelines
Oral semaglutide is the only available oral GLP-1 agonist for weight loss, with modest efficacy of approximately 15.1% weight loss, and its use is recommended for patients who cannot tolerate injectable formulations or have limited access to them 1. When comparing oral GLP-1 agonists for weight loss, it is essential to consider the limited options available. Currently, only semaglutide (Rybelsus) is FDA-approved for oral administration, primarily for type 2 diabetes management rather than weight loss specifically.
Efficacy Comparison
- Oral semaglutide has demonstrated a mean weight loss of 15.1% in a clinical trial, which is significantly higher than the weight loss achieved with other oral medications 1.
- In contrast, injectable GLP-1 agonists like semaglutide (Wegovy) and liraglutide (Saxenda) have shown superior efficacy for weight management, with weight loss ranging from 15-20% 1.
Side Effects Comparison
- The side effects of oral semaglutide are similar to those of injectable formulations, including nausea, vomiting, diarrhea, abdominal pain, and constipation, although generally less severe 1.
- Liraglutide has been associated with gastrointestinal side effects, esophageal reflux, injection site reactions, elevated heart rate, and hypoglycemia 1.
Recommendations
- For patients seeking significant weight loss, injectable GLP-1 agonists currently offer superior efficacy compared to the available oral option 1.
- However, oral semaglutide may be a viable alternative for patients who cannot tolerate injectable formulations or have limited access to them, considering its modest efficacy and similar side effect profile to injectable formulations 1.
Future Developments
- Several pharmaceutical companies are developing additional oral GLP-1 options, including oral versions of tirzepatide, which may offer improved efficacy and safety profiles in the future 1.
From the Research
Efficacy of Oral GLP-1 Agonist Drugs for Weight Loss
- Semaglutide has shown significant efficacy in weight reduction, with superior results compared to other treatments in the same class 2.
- Studies such as SUSTAIN, PIONEER, and STEP have demonstrated the superiority of semaglutide in weight loss compared to other GLP-1 receptor agonists and anti-obesity drugs 2, 3.
- Semaglutide has demonstrated the largest weight loss of any obesity medication to date, with reductions of approximately 15% of initial weight at 68 weeks 4.
Side Effects of Oral GLP-1 Agonist Drugs
- The most common adverse events associated with semaglutide are gastrointestinal, with nausea and diarrhea being the most frequently reported manifestations 5, 6.
- Semaglutide increases the risk of biliary disease (cholelithiasis) and may cause mild-to-moderate and transient gastrointestinal disturbances 5.
- The risk of hypoglycemia is low, and the cardiovascular safety profile of oral semaglutide is likely to be similar to that of subcutaneous semaglutide 6.
Comparison of Oral GLP-1 Agonist Drugs
- Semaglutide is the only GLP-1RA currently available as both subcutaneous and oral formulation 5.
- The oral formulation of semaglutide has shown promising initial results, with higher doses (50 mg) showing weight losses comparable to those of subcutaneous administration 2.
- There are no other oral GLP-1 agonist drugs available for weight loss, making semaglutide the primary option in this class 5, 2, 4, 3, 6.