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

• Published in: Endocrinology, diabetes & metabolism diabetes & metabolism, 2021-07, Vol.4 (3), p.e00259-n/a
• Main Authors: Evans, Lyndon Marc, Mellbin, Linda, Johansen, Pierre, Lawson, Jack, Paine, Abby, Sandberg, Anna
• Format: Article
• Language: English
• Subjects: Antidiabetics; Cardiology; Cardiovascular disease; Cardiovascular Diseases - etiology; Cardiovascular Diseases - prevention & control; cardiovascular risks; Diabetes; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; GLP‐1 receptor agonist; Glucagon-Like Peptides - analogs & derivatives; Glucose; Humans; Hypoglycemic Agents; Immunoglobulin Fc Fragments; Medicin och hälsovetenskap; Original; Original s; Patients; Recombinant Fusion Proteins; Risk factors; type 2 diabetes
• ISSN: 2398-9238; 2398-9238
• DOI: 10.1002/edm2.259

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. In the absence of head‐to‐head cardiovascular (CV) outcome trials comparing semaglutide and dulaglutide, the aim of this study was to compare the relative effect of these treatments on major adverse cardiovascular events (MACE) using a matching‐adjusted indirect comparison. Reduction in 3‐point MACE was greater with semaglutide versus dulaglutide, although not statistically significant in the population of patients with and without prior CV disease. ​