A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving Basal Insulin.

INTRODUCTION: Once-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin. METHODS: A systematic literature review was performed to identify all trials of GLP-1 RAs as an add-on to basal insulin in patients with T2D. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in an NMA), including the change from baseline in glycated hemoglobin (HbA), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework. RESULTS: In total, eight studies were included across the base-case analyses. The results demonstrate that once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA (- 0.88% to - 1.39% vs comparators) and weight (- 1.49 to - 4.69 kg vs comparators) and similar odds of experiencing nausea, vomiting, or diarrhea vs all GLP-1 RA comparators. Once-weekly semaglutide 1.0 mg was also equally effective at reducing systolic blood pressure compared with liraglutide 1.8 mg. Once-weekly semaglutide 0.5 mg significantly reduced HbA vs the majority of other GLP-1 RAs, except liraglutide 1.8 mg QD. The odds of experiencing nausea were significantly lower with once-weekly semaglutide 0.5 mg compared with all GLP-1 RA comparators. CONCLUSION: Once-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA and weight from baseline after 6 months of treatment. The efficacy of once-weekly semaglutide is not associated with a significant increase in the incidence of gastrointestinal side-effects vs other GLP-1 RAs. FUNDING: Novo Nordisk.