From the Guidelines
Rybelsus (oral semaglutide) is the recommended oral GLP-1 receptor agonist for type 2 diabetes treatment. It is available in 3 mg, 7 mg, and 14 mg tablets, with treatment typically starting at 3 mg once daily for one month, then increasing to 7 mg once daily, with a possible further increase to 14 mg if needed for glycemic control. Rybelsus should be taken on an empty stomach when first waking up, with no more than 4 ounces of plain water, and patients should wait at least 30 minutes before consuming food, beverages, or other medications. This timing is crucial because food significantly reduces the absorption of oral semaglutide. Rybelsus works by stimulating insulin secretion when blood glucose is elevated, suppressing glucagon secretion, slowing gastric emptying, and reducing appetite, which helps lower blood glucose levels and may contribute to weight loss. Unlike injectable GLP-1 receptor agonists, Rybelsus offers the convenience of oral administration while providing similar benefits for glycemic control and potential weight reduction in type 2 diabetes management.
The recommendation for Rybelsus is based on the most recent and highest quality study available, which demonstrated its efficacy and safety in patients with type 2 diabetes 1. The study showed that oral semaglutide was noninferior to placebo for the primary composite outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke, with a hazard ratio of 0.79 (95% CI 0.57-1.11; P < 0.001 for noninferiority) 1. Additionally, the study found that oral semaglutide reduced the risk of major adverse cardiovascular events, including cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, compared to placebo 1.
Key points to consider when prescribing Rybelsus include:
- Starting dose: 3 mg once daily for one month, then increasing to 7 mg once daily, with a possible further increase to 14 mg if needed for glycemic control
- Administration: Take on an empty stomach when first waking up, with no more than 4 ounces of plain water, and wait at least 30 minutes before consuming food, beverages, or other medications
- Mechanism of action: Stimulates insulin secretion, suppresses glucagon secretion, slows gastric emptying, and reduces appetite
- Benefits: Lowers blood glucose levels, may contribute to weight loss, and offers the convenience of oral administration
Overall, Rybelsus is a valuable treatment option for patients with type 2 diabetes, offering a convenient and effective way to manage blood glucose levels and reduce the risk of cardiovascular events.
From the FDA Drug Label
Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner.
The oral semaglutide recommended for type 2 diabetes is semaglutide (PO), a Glucagon-like peptide-1 receptor agonist, which stimulates insulin secretion and lowers glucagon secretion in a glucose-dependent manner 2.
- Key benefits of semaglutide include:
- Reductions in fasting and postprandial glucose concentrations
- Increase in first-and second-phase insulin secretion
- Lowering of fasting and postprandial glucagon concentrations
- Delay in early postprandial gastric emptying, reducing the rate at which glucose appears in the circulation postprandially.
From the Research
Oral Semaglutide for Type 2 Diabetes
- Oral semaglutide, marketed under the brand name Rybelsus®, is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated for the treatment of type 2 diabetes 3, 4, 5.
- It is available in three doses (3,7, and 14 mg) and can be used as monotherapy or in combination with other glucose-lowering agents, including insulin 4.
- The efficacy and safety of oral semaglutide have been demonstrated in several clinical trials, including the PIONEER program, which showed improved glycemic control, weight loss, and a low risk of hypoglycemia 3, 4, 6.
- Oral semaglutide has been shown to have a cardiovascular safety profile similar to that of subcutaneous semaglutide, with a noninferiority result versus placebo in a cardiovascular outcomes trial 3, 6.
Mechanism of Action and Benefits
- Oral semaglutide works by augmenting hyperglycemia-induced insulin secretion, suppressing glucagon secretion, and delaying gastric emptying, which helps to reduce post-meal glycemic increments and promote weight loss 7.
- The use of oral semaglutide may facilitate earlier treatment with GLP-1 receptor agonists in the diabetes treatment cascade, due to its oral administration and potential for wider acceptance by patients and healthcare professionals 3.
- GLP-1 receptor agonists, including oral semaglutide, are recommended as a preferred first injectable glucose-lowering therapy for type 2 diabetes, due to their effectiveness in reducing HbA1c and body weight, and their potential to prevent cardiovascular events 7.