An indirect treatment comparison of the efficacy of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg

Abstract

Aim To compare the effects of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg on HbA1c and body weight in patients with type 2 diabetes. Materials and Methods A Bucher indirect comparison was conducted to compare efficacy outcomes of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg using published results from the SUSTAIN 7 and AWARD‐11 trials. Sensitivity analyses using individual patient data from SUSTAIN 7 and aggregate data from AWARD‐11 were conducted to explore the impact of adjustment for cross‐trial imbalances in baseline characteristics. Results Semaglutide 1.0 mg significantly reduced HbA1c versus dulaglutide 3.0 mg, with an estimated treatment difference (ETD) of −0.24%‐points (95% confidence interval [CI] −0.43, −0.05), with comparable reductions in HbA1c versus dulaglutide 4.5 mg with an ETD of −0.07%‐points (95% CI −0.26, 0.12). Semaglutide 1.0 mg significantly reduced body weight versus dulaglutide 3.0 and 4.5 mg with an ETD of −2.65 kg (95% CI −3.57, −1.73) and −1.95 kg (95% CI −2.87, −1.03), respectively. Sensitivity analyses supported the primary analysis findings. Conclusions This indirect comparison showed significantly greater reductions in HbA1c with semaglutide 1.0 mg versus dulaglutide 3.0 mg and comparable HbA1c reductions versus dulaglutide 4.5 mg. Semaglutide 1.0 mg significantly reduced body weight versus both dulaglutide 3.0 and 4.5 mg. With several glucagon‐like peptide‐1 receptor agonists available, information regarding their comparative efficacy can be valuable to clinicians.

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

“…Because only published aggregate data were available for AWARD-11, this is in line with the approach that would be used in other population-adjusted methods, such as MAIC, in which IPD would be used to match baseline summary statistics to aggregate data ( 21 ). This is also aligned with the MAIC conducted as a supplementary analysis in the recent publication indirectly comparing semaglutide 1.0 mg with dulaglutide 3.0 mg and 4.5 mg ( 13 ). The impact of using the SUSTAIN FORTE and SUSTAIN 7 populations was explored in supplementary analyses, all of which supported the findings of the main analysis.…”

“…In the analysis, significantly greater reductions in HbA 1c were demonstrated with semaglutide 1.0 mg vs dulaglutide 3.0 mg, and comparable reductions in HbA 1c were shown for semaglutide 1.0 mg and dulaglutide 4.5 mg. Significantly greater reductions in body weight were also demonstrated with semaglutide 1.0 mg vs both doses of dulaglutide ( 13 ). However, in the absence of a head-to-head trial comparing semaglutide 2.0 mg with dulaglutide 3.0 mg and 4.5 mg, this is the first comparison of these doses of semaglutide and dulaglutide.…”

“…Dulaglutide 3.0 mg and 4.5 mg were investigated in AWARD-11 ( 11 ) and subsequently approved in 2020 and 2021 by the FDA and EMA, respectively ( 8 , 12 ). Semaglutide 1.0 mg has previously been compared with dulaglutide 3.0 mg and 4.5 mg using a Bucher indirect treatment comparison (ITC) ( 13 ). Semaglutide 2.0 mg has also been investigated in SUSTAIN FORTE ( 14 ) and is currently under review by the FDA and EMA.…”

Indirect treatment comparisons: Choosing the right tool for the job

“…3 A more interesting comparison, not reported by Tham et al, 1 would be to contrast the result of patients remaining on semaglutide OW for the full 52 weeks with the 52-week result after switching to 3.0 or 4.5 mg dulaglutide OW at 26 weeks. Third, even if Tham et al 1 had addressed the same question as Pratley et al, 2 it cannot be supposed that the PK/PD model predictions would be any less biased than the results of a wellconducted NMA. 4 One key bias-reducing advantage of NMA methods is that differences in trial populations are addressed by the contrasting placebo-adjusted effects rather than the absolute effects.…”

“…First, methodology preferences aside, the questions addressed by Tham et al 1 and by Pratley et al 2 are different. Tham et al 1 posed the question of whether additional improvements in HbA1c and body weight are possible when switching to dulaglutide 3.0 or 4.5 mg OW after 26 weeks of treatment with semaglutide 0.5 or 1.0 mg OW, relative to the clinical outcome at 26 weeks.…”