Real-world Evidence on Oral Semaglutide for the Management of Type 2 Diabetes. A Narrative Review for Clinical Practice.

Purpose: Oral semaglutide is the first oral glucagon-like peptide-1 receptor agonist (GLP-1RA) available for type 2 diabetes mellitus (T2DM) management, whose effectiveness and tolerability have extensively been demonstrated in the PIONEER clinical trial program. Nevertheless, data from real-world are crucial to evaluate treatment performance under routine care. The aim of this narrative review is to summarize available evidence regarding real-world utilization patterns of oral semaglutide, and discuss efficacy, safety, and dosing regimen data in routine scenarios.

Methods: We searched PubMed for real-world studies evaluating oral semaglutide up to August 2024, and specific search terms were: "oral semaglutide," and "real-world studies" or "observational studies" or "retrospective studies".

Findings: 19 real-world studies were included in the narrative review. In real-world settings, oral semaglutide provided significant glycemic (median HbA1c reduction at 6 months of 1%) and weight (median body weight reduction of 2 to 3 kg) benefits across the spectrum of T2DM, aligning with pre-clinical evidence from the PIONEER program. No new tolerability and safety issue has emerged from oral semaglutide administration in routine clinical practice.

Implications: Oral semaglutide constitutes an effective and safe option for T2DM management, and its increased acceptance has the potential to favor the early introduction of GLP-1RAs along the disease course. Nevertheless, continuous evaluation of real-world data is critical to better define the optimal positioning of oral semaglutide along T2DM trajectory and fully exploit its potential in everyday clinical practice.