Orally Administered Semaglutide Versus GLP-1 RAs in Patients with Type 2 Diabetes Previously Receiving 1-2 Oral Antidiabetics: Systematic Review and Network Meta-Analysis

Introduction Orally administered semaglutide is the first glucagon-like peptide 1 receptor agonist (GLP-1 RA) for oral administration. As head-to-head trials assessing orally administered semaglutide as an add-on to 1-2 oral antidiabetic drugs (OADs) vs other GLP-1 RAs are limited, a network meta-analysis (NMA) was performed to assess the relative efficacy and safety of orally administered semaglutide 14 mg once-daily (QD) vs injectable GLP-1 RAs in patients with type 2 diabetes inadequately controlled on 1-2 OADs. Methods A systematic literature review was conducted to identify randomised controlled trials of GLP-1 RAs in patients inadequately controlled on 1-2 OADs. Data at 26 +/- 4 weeks were extracted for efficacy and safety outcomes feasible for the NMA: change from baseline in glycated haemoglobin (HbA(1c)), weight, HbA(1c) target levels (< 7.0% and <= 6.5%), blood pressure, and any gastrointestinal adverse events specified in system organ class. Data were synthesised using NMA and a Bayesian framework. Results In total, 27 studies were included in the analyses. Orally administered semaglutide 14 mg QD was associated with significantly greater reductions in HbA(1c) vs most comparators, and numerically greater reductions vs semaglutide 0.5 mg once-weekly (QW), dulaglutide 1.5 mg QW and liraglutide 1.8 mg QD. HbA(1c) reductions with semaglutide 1 mg QW were numerically greater than those with orally administered semaglutide 14 mg QD. Reductions in body weight for orally administered semaglutide 14 mg QD were significantly greater than all comparators except semaglutide QW (both doses). Orally administered semaglutide QD 14 mg was associated with statistically similar odds of experiencing gastrointestinal adverse events vs injectable GLP-1 RAs. Conclusion Orally administered semaglutide 14 mg QD as an add-on to 1-2 OADs is one of the most efficacious GLP-1 RAs for reducing HbA(1c) and body weight at 26 +/- 4 weeks. Orally administered semaglutide 14 mg QD is well tolerated, with a safety profile in line with the GLP-1 RA class. Funding Novo Nordisk.