Background: In the absence of head-to-head evidence, an indirect treatment comparison (ITC) using individual-level participant data was conducted to provide evidence of the comparative cardiovascular (CV) protective effect of liraglutide vs semaglutide in subjects with type 2 diabetes.

Methods: CV outcomes trials (CVOTs) were identified for comparators of interest. LEADER was a randomised controlled trial studying the CV protective effect of liraglutide vs placebo. Similarly, two CVOTs comparing semaglutide with placebo were identified: SUSTAIN 6 and PIONEER 6. Time to first 3-point major adverse CV events (3P-MACE) (adjudicated) was the primary outcome in all trials and was chosen as the primary outcome for the ITC. Potential effect modifiers (baseline indicators of prior CV disease, albumin:creatinine ratio, estimated glomerular filtration rate) were identified in the literature and adjusted for in the ITC. A fixed-effects ITC using individual participant data was conducted in a Bayesian setting. Missing data for potential effect modifiers were imputed using multiple imputation (20 imputations). Comparisons were summarised as cause-specific hazard ratios (HRs). Population-average relative treatment effects between liraglutide and semaglutide were reported for each of the three populations corresponding to the three studies.

Results: The ITC showed that the relative risk of semaglutide vs liraglutide for the occurrence of 3P-MACE in the LEADER population favoured semaglutide: HR 0.73 (95% credible interval [CrI]: 0.56;0.94); results also favoured semaglutide in the SUSTAIN 6 (HR 0.76 [95% CrI: 0.59;0.97]) and PIONEER 6 (HR 0.78 [95% CrI: 0.60;1.00]) populations.

Conclusion: The results demonstrated a risk reduction of CV events (3P-MACE) for semaglutide vs liraglutide of 22-27% depending on the population studied. These results may have implications for clinical practice.


B.Chubb: Employee; Novo Nordisk A/S, Stock/Shareholder; Novo Nordisk A/S. M.Bøg: Employee; Lundbeck, Novo Nordisk.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at