An Indirect Treatment Comparison of Semaglutide 2.0 mg vs Dulaglutide 3.0 mg and 4.5 mg Using Multilevel Network Meta-regression

Aims: Currently, no head-to-head data are available comparing semaglutide 2.0 mg with dulaglutide 3.0 mg or 4.5 mg. We conducted an indirect treatment comparison (ITC) of their effects on glycated hemoglobin (HbA1c) and body weight in patients with type 2 diabetes. Materials and methods: Multilevel network meta-regression was conducted, based on a connected evidence network of published results from the A Study of the Efficacy and Safety of Dulaglutide (LY2189265) in Participants With Type 2 Diabetes 11 trial and individual patient data from the A Research Study to Compare Two Doses of Semaglutide Taken Once Weekly in People With Type 2 Diabetes (SUSTAIN) and SUSTAIN 7 trials. Results: Semaglutide 2.0 mg significantly reduced HbA1c vs dulaglutide 3.0 mg and 4.5 mg, with estimated treatment differences (ETDs) of -0.44% points (95% credible interval [CrI], -0.68 to -0.19) and -0.28% points (95% CrI, -0.52 to -0.03), respectively. Semaglutide 2.0 mg also significantly reduced body weight vs dulaglutide 3.0 mg and 4.5 mg with ETDs of -3.29 kg (95% CrI, -4.62 to -1.96) and -2.57 kg (95% CrI, -3.90 to -1.24), respectively. Odds of achieving HbA1c<7.0% were significantly greater for semaglutide 2.0 vs dulaglutide 3.0 mg (odds ratio [OR]: 2.23 [95% CrI, 1.15-3.90]), whereas this did not reach significance for semaglutide 2.0 mg vs dulaglutide 4.5 mg (OR: 1.58 [95% CrI, 0.82-2.78]). Sensitivity analyses supported the main analysis findings. Conclusions: This ITC demonstrated significantly greater reductions from baseline in HbA1c and body weight with semaglutide 2.0 mg vs dulaglutide 3.0 mg and 4.5 mg. The findings of this study provide important comparative effectiveness information until randomized head-to-head studies become available.