A population‐adjusted indirect comparison of cardiovascular benefits of once‐weekly subcutaneous semaglutide and dulaglutide in the treatment of patients with type 2 diabetes, with or without established cardiovascular disease

Endocrinology, Diabetes & Metabolism

Lyndon Marc Evans¹  Linda Mellbin²  Pierre Johansen³  Anna Sandberg³  Jack Lawson³  Abby Paine⁴ 

[1] Cardiff and Vale University Cardiff UK;Department of Medicine Solna Karolinska Institutet Stockholm Sweden;Novo Nordisk A/S Søborg Denmark;Zedediah Consulting on behalf of DRG Abacus (part of Clarivate) Wokingham UK;

关键词: cardiovascular risks;    GLP‐1 receptor agonist;    type 2 diabetes;   

DOI  :  10.1002/edm2.259

来源: DOAJ

【 摘 要 】

Abstract Introduction Cardiovascular (CV) effects of once‐weekly subcutaneous (s.c.) semaglutide 0.5 and 1 mg and dulaglutide 1.5 mg are reported in their respective placebo‐controlled cardiovascular outcome trials (CVOTs), SUSTAIN 6 and REWIND. There is no head‐to‐head CVOT comparing these treatments and heterogeneity between their CVOTs renders conventional indirect comparison inappropriate. Therefore, a matching‐adjusted indirect comparison (MAIC) was performed to compare the effects of s.c. semaglutide and dulaglutide on major adverse cardiovascular events (MACE) in patients with and without established cardiovascular disease (CVD). Methods Individual patient data from SUSTAIN 6 were matched with aggregate data from REWIND, using a propensity score method to balance baseline effect‐modifying patient characteristics. Hazard ratios (HRs) for three‐point (3P) MACE (CV death, non‐fatal myocardial infarction, non‐fatal stroke), anchored via placebo, were then indirectly compared between balanced populations. Sensitivity analyses were performed to test the robustness of the main analysis. Results After matching, included effect modifiers were balanced. In the main analysis, s.c. semaglutide was associated with a statistically significant 35% reduction in 3P MACE versus placebo (HR, 0.65 [95% confidence interval [CI]; 0.48, 0.87]) and nonsignificantly greater reduction (26%) versus dulaglutide (HR, 0.74 [95% CI; 0.54, 1.01]). Results were supported by all sensitivity analyses. Conclusions This study demonstrated a statistically significant lower risk of 3P MACE for s.c. semaglutide versus placebo, in a population with lower prevalence of pre‐existing CVD than that in the pre‐specified primary analysis in SUSTAIN 6. Reduction in 3P MACE with s.c. semaglutide was greater than with dulaglutide, although not statistically significant.

【 授权许可】

Unknown