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

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.