Clinical Perspectives on the Use of Subcutaneous and Oral Formulations of Semaglutide

Abstract

Early and effective glycemic control can prevent or delay the complications associated with type 2 diabetes (T2D). The benefits of glucagon-like peptide-1 receptor agonists (GLP-1RAs) are becoming increasingly recognized and they now feature prominently in international T2D treatment recommendations and guidelines across the disease continuum. However, despite providing effective glycemic control, weight loss, and a low risk of hypoglycemia, GLP-1RAs are currently underutilized in clinical practice. The long-acting GLP-1RA, semaglutide, is available for once-weekly injection and in a new once-daily oral formulation. Semaglutide is an advantageous choice for the treatment of T2D since it has greater efficacy in reducing glycated hemoglobin and body weight compared with other GLP-1RAs, has demonstrated benefits in reducing major adverse cardiovascular events, and has a favorable profile in special populations (e.g., patients with hepatic impairment or renal impairment). The oral formulation represents a useful option to help improve acceptance and adherence compared with injectable formulations for patients with a preference for oral therapy, and may lead to earlier and broader use of GLP-1RAs in the T2D treatment trajectory. Oral semaglutide should be taken on an empty stomach, which may influence the choice of formulation. As with most GLP-1RAs, initial dose escalation of semaglutide is required for both formulations to mitigate gastrointestinal adverse events. There are also specific dose instructions to follow with oral semaglutide to ensure sufficient gastric absorption. The evidence base surrounding the clinical use of semaglutide is being further expanded with trials investigating effects on diabetic retinopathy, cardiovascular outcomes, and on the common T2D comorbidities of obesity, chronic kidney disease, and non-alcoholic steatohepatitis. These will provide further information about whether the benefits of semaglutide extend to these other indications.

Efficacy and Safety of Subcutaneous and Oral Semaglutide Administration in Patients With Type 2 Diabetes: A Meta-Analysis

“…It can directly stimulate insulin secretion from pancreatic β-cells while suppressing glucagon release from pancreatic α-cells (Cornell, 2020). Specifically, the structure and pharmacokinetics of semaglutide are distinct from other GLP-1 RAs, as it shows 94% sequence homology with native GLP-1, sufficiently high GLP-1 receptor affinity, and exhibits an extended plasma halflife of approximately 1 week (Lau et al, 2015;Gallwitz and Giorgino, 2021). Second, semaglutide suppresses appetite and consequently leads to reduced energy intake through direct and secondary effects in the hypothalamus and area postrema of the brain, both of which are involved in appetite regulation and energy metabolism (Gabery et al, 2020).…”

Therapeutic Potential of Glucagon-like Peptide-1 Agonists in Polycystic Ovary Syndrome: From Current Clinical Evidence to Future Perspectives

“…Furthermore, semaglutide 2.4 mg demonstrated higher efficacy in body weight reduction and more favorable clinical characteristics compared to all other GLP-1RAs making this long-acting GLP-1RA an advantageous choice [ 81 ]. Semaglutide could be the best option also in PCOS, yet robust clinical trials are needed [ 82 ].…”

Therapie des Typ-2-Diabetes

“…Eine Potenzierung von Nebenwirkungen wurde unter oraler Dreifachkombination nicht beobachtet; sie entsprechen im Wesentlichen denjenigen, die bei Monotherapie für die jeweilige Substanz beobachtet werden. Eine neue Option ist die Kombination eines „klassischen“ oralen Antidiabetikums mit Semaglutid oral 50 51 .…”