Author + information
- Sean L. Zheng, BM, BCh, MA∗ ( and )
- Alistair J. Roddick, BSc
- ↵∗Faculty of Medicine, Imperial College London, Department of Cardiology, King’s College Hospital NHS Foundation Trust, 33 Willcott Road, London, SE5 9RS, United Kingdom
Kramer et al. (1) demonstrated, using a network meta-analysis (NMA) of 9 cardiovascular outcome randomized controlled trials (RCTs), that sodium-glucose co-transporter (SGLT)-2 inhibitors were associated with a reduced risk of heart failure hospitalization compared with glucagon-like peptide (GLP)-1 receptor agonists, dipeptidyl peptidase (DPP)-4 inhibitors, and placebo (1). These findings mirror our own Bayesian NMA, which was published recently in the Journal of the American Medical Association, and examined the cardiovascular efficacy and safety profile of these 3 classes of glucose-lowering agents (2). Heart failure events were tested as a secondary efficacy outcome in our study, with broadly similar results to those of Kramer et al. (1).
NMA is a powerful statistical approach that allows indirect comparisons between treatments that share common comparators. It is particularly useful when treatments have not been compared directly with those in RCTs, as is the case for the newer diabetes therapies. With so many treatment options available for type 2 diabetes, estimates of treatment effects derived from this method provide important information that clinicians and patients can use to make informed decisions. However, NMA does have several limitations, with one key assumption being that baseline patient characteristics are the same across trials (transitivity) (3). Careful assessment of relevant baseline characteristics between treatment arms is therefore an important first step in producing a NMA. Notably, 2 trials included in this study, EXAMINE (Examination of Cardiovascular Outcomes with Alogliptin versus Standard of Care) (4) (alogliptin, DPP-4 inhibitor) and ELIXA (Evaluation of Lixisenatide in Acute Coronary Syndrome) (5) (lixisenatide, GLP-1 receptor agonist), enrolled patients with a recent acute coronary event. These trials had distinctly different patient populations than those in the remaining 7 trials, which would affect treatment group characteristics (e.g., baseline cardiovascular risk and heart failure status) that could potentially affect heart failure outcomes. Sensitivity analysis excluding these 2 trials is one method that can act to reassure readers that their inclusion does not affect overall study conclusions. We undertook sensitivity analysis to that effect in our study, and demonstrated no difference in the overall findings (2). Associations that demonstrated reductions in heart failure events with SGLT-2 inhibitors compared with DPP-4 inhibitors, GLP-1 receptor agonists, and placebo remained.
Overall, the evidence available from RCTs and observational studies suggest that SGLT-2 inhibitors have the greatest efficacy on heart failure outcomes in patients with type 2 diabetes and elevated cardiac risk. NMAs, such as this study by Kramer et al. (1), provide useful supportive observational data derived from randomized evidence, although investigators and readers should be aware of the limitations and assumptions of such methods.
Please note: The authors have reported that they have no relationships relative to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
- Kramer C.K.,
- Ye C.,
- Campbell S.,
- Retnakaran R.
- Zheng S.L.,
- Roddick A.J.,
- Aghar-Jaffar R.,
- et al.