From the Guidelines
Oral GLP-1 receptor agonists, such as semaglutide, are a recommended treatment option for type 2 diabetes and weight management, due to their ability to improve glycemic control, reduce weight, and decrease the risk of cardiovascular events. The most recent and highest quality study, published in 2024, demonstrated the efficacy of GLP-1 receptor agonists in reducing cardiovascular outcomes in people with type 2 diabetes at high risk for cardiovascular disease or with established cardiovascular disease 1.
Key Findings
- The LEADER trial showed that liraglutide, a GLP-1 receptor agonist, reduced the primary composite outcome of MI, stroke, or cardiovascular death by 13% compared to placebo 1.
- The SUSTAIN-6 trial demonstrated that semaglutide, another GLP-1 receptor agonist, reduced the primary outcome of cardiovascular death, nonfatal MI, or nonfatal stroke by 26% compared to placebo 1.
- Oral semaglutide has been shown to be effective in reducing weight and improving weight-related comorbidities, with a mean weight loss of 15.1% compared to 2.4% with placebo 1.
Recommendations
- Oral semaglutide should be considered as a treatment option for patients with type 2 diabetes and obesity, due to its ability to improve glycemic control, reduce weight, and decrease the risk of cardiovascular events.
- Patients should be advised to take oral semaglutide on an empty stomach with no more than 4 ounces of water, at least 30 minutes before the first food, beverage, or other oral medications of the day to ensure proper absorption.
- Common side effects of oral semaglutide include nausea, vomiting, diarrhea, abdominal pain, and decreased appetite, which typically improve over time.
Important Considerations
- Oral semaglutide is contraindicated in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, and caution is advised in those with pancreatitis history or severe gastrointestinal disease.
- Long-term use of oral semaglutide is necessary to maintain weight loss, as significant weight regain has been observed after cessation of treatment 1.
From the Research
Oral GLP-1 Receptor Agonists
- Oral GLP-1 receptor agonists, such as semaglutide, have been developed for the treatment of type 2 diabetes 2, 3, 4, 5, 6
- Semaglutide is available in both subcutaneous and oral dosage forms, with the oral form being the first approved oral GLP-1 receptor agonist 3, 4
- Oral semaglutide has been shown to have efficacy and safety profiles similar to those of other GLP-1 receptor agonists 4, 5, 6
Mechanism of Action and Effects
- GLP-1 receptor agonists, including oral semaglutide, work by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, decelerating gastric emptying, and reducing calorie intake and body weight 2
- Oral semaglutide has been shown to lower glycated hemoglobin (HbA1c) levels, reduce body weight, and prevent cardiovascular events 3, 4, 6
- The use of oral semaglutide has also been associated with a low risk of hypoglycemia 5, 6
Administration and Dosage
- Oral semaglutide should be taken on an empty stomach upon waking with a sip of plain water and at least 30 minutes before the first food, beverage, or other oral medications of the day 5
- The most common adverse effects of oral semaglutide are gastrointestinal, including nausea, diarrhea, and vomiting 5, 6
- Pharmacists should counsel patients prescribed oral semaglutide about optimal oral dosing, expected therapeutic response, and effective strategies to mitigate potential gastrointestinal adverse events 5
Clinical Studies and Guidance
- Clinical studies, such as PIONEER 4 and PIONEER 8, have compared oral semaglutide with injectable GLP-1 receptor agonists and placebo in patients with type 2 diabetes 6
- Guidance on the use of oral semaglutide in primary care has been provided, including its use in patients requiring treatment intensification after oral therapy or as add-on to insulin 6