Meta-analysed numbers needed to treat of novel antidiabetic drugs for cardiovascular outcomes

Abstract

Aims: Absolute treatment effects-i.e. numbers needed to treat (NNTs)-of novel antidiabetic drugs for cardiovascular outcomes have not been comprehensively evaluated. We aimed to perform a meta-analysis of digitalized individual patient outcomes to display and compare absolute treatment effects.

Methods and results: Individual patient time-to-event information from Kaplan-Meier plots of cardiovascular mortality (CM) and/or hospitalization for heart failure (HHF) endpoints from cardiovascular outcome trials (CVOTs) evaluating dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium glucose transporter 2 (SGLT2) inhibitors vs. placebo were digitalized using WebPlotDigitizer 4.2 and the R code of Guyot et al.; Weibull regression models were generated, validated, and used to estimate NNT for individual trials; random-effects meta-analysis generated Meta-NNT with 95% confidence intervals. Sixteen CVOTs reported time-to-event information (14 in primary diabetes and 2 in primary heart failure populations). Thirteen studies including 96 860 patients were meta-analysed for CM: At the median follow-up of 30 months, Meta-NNTs were 178 (64 to ∞ to -223) for DPP-4 inhibitors, 261 (158 to 745) for GLP-1 receptor agonists, and 118 (68 to 435) for SGLT2 inhibitors. Ten studies including 96 128 patients were meta-analysed for HHF: At the median follow-up of 29 months, estimated Meta-NNTs were -644 (229 to ∞ to -134) for DPP-4 inhibitors, 441 (184 to ∞ to -1100) for GLP-1 receptor agonists, and 126 (91 to 208) for SGLT2 inhibitors. SGLT2 inhibitors were especially effective for HHF in primary heart failure populations [Meta-NNT 25 (19 to 39)] vs. primary diabetes populations [Meta-NNT 233 (167 to 385)] at 16 months of follow-up.

Conclusions: We found only modest treatment benefits of GLP-1 receptor agonists and SGLT2 inhibitors for CM and HHF in primary type 2 diabetes mellitus populations. In primary heart failure populations, SGLT2 inhibitor benefits were substantial and comparable in efficacy to established heart failure medication.

Keywords: Absolute treatment effect; GLP-1 receptor agonist; Heart failure; Meta-analysis; Number needed to treat; SGLT2 inhibitor.