Oral Semaglutide
Semaglutide is a GLP-1 agonist. This is a mimic of a hormone naturally produced and helps us feel full and satiated. Until now all GLP-1 medications for weight loss that are commercially available have been injections. Based on recent studies, oral semaglutide for weight loss requires doses that are much higher for weight management than for diabetes management in lowering blood sugar. Compounded oral semaglutide in liquid or troche form has been used for some time now with success although the observation has been less potent than injectable versions. The difference in this commercially available formula and compounded versions is the site of absorption and dose. When the medication is swallowed in pill form by mouth, the absorption is significantly less so the dose needs to be much higher. When troche or liquid is used, the medication is absorbed in the mouth and lower doses can be used. That being said, nobody is going to do a huge randomized controlled trial on compounded medication. It is however reassuring to me that we have more evidence that oral semaglutide can be effective for weight loss. I am thinking this could be helpful in step down therapy which can reduce the long term costs of GLP-1 weight loss medication. Oral semaglutide can be a viable option for GLP-1 naive patients looking to support their weight loss goals in combination with dietary intervention and exercise and all the other factors that influence our weight such as the microbiome, hormone balance and toxic burden.
Patients either overweight with body mass index of 27 or greater with weight related medical problems or patients with body mass index of 30 or greater were given either placebo pills + lifestyle counseling or Semaglutide 25 mg + lifestyle counseling. Those in the oral semaglutide group at the end of 64 weeks lost an average of 13.6%. The main side effects observed in the treated group was as expected gastrointestinal. Interestingly the majority of the patients in this study were women.
Dosing recommendations for Wegovy-Pill or oral Semaglutide are to titrate up starting at 1.5 mg day 1-30 then 4 mg for day 31-60, followed by 9 mg for day 61-90 and then 25 mg daily after that. If lower doses are working or if there are side effects it makes sense to stay longer at the lower doses however as you can see in the study above, the 25 mg dose is where the full treatment effect was noted.
It is important that these medications are used in combination with lifestyle changes for best results. There is a risk of loss of lean body mass and increased side effects when not combined with good quality nutrition and exercise.
Wharton S, Lingvay I, Bogdanski P, Duque do Vale R, Jacob S, Karlsson T, Shaji C, Rubino D, Garvey WT; OASIS 4 Study Group. Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity. N Engl J Med. 2025 Sep 18;393(11):1077-1087. doi: 10.1056/NEJMoa2500969. PMID: 40934115.
