Absolute treatment effects for the primary outcome and all-cause mortality in the cardiovascular outcome trials in type 2 diabetes: a meta-analysis of individual patient data

Abstract

Abstract Background and purpose Treatment effects from the large cardiovascular outcome trials (CVOTs) in diabetes are almost exclusively communicated as hazard ratios, although reporting guidelines recommend to report treatment effects also on an absolute scale, e.g. as numbers needed to treat (NNT). We aimed to analyze NNT in CVOTs of novel oral antidiabetic drugs comparing dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, or sodium-glucose cotransporter-2 (SGLT2) inhibitors to placebo. Methods and results We extracted individual time-to-event information for the primary outcome and all-cause mortality from 19 CVOTs that compared DPP-4 inhibitors, GLP-1 receptor agonists, or SGLT2 inhibitors to placebo. We estimated Weibull models for each trial and outcome and derived monthly NNTs. NNTs were summarized across all trials and within drug-classes by random effects meta-analysis methods. Treatment effects in the CVOTs appear smaller if they are reported as NNTs: Overall, 60 (95%-CI: 40–124) patients have to be treated for 29 months (the median follow-up time across all trials) to avoid a single event of the primary outcome, and 101 (95%-CI: 69–191) patients have to be treated for 39 months to avoid a single death. Conclusion We found that the respective treatment effects of novel oral antidiabetic drugs look less impressive when communicated on an absolute scale, as numbers needed to treat. For a valid overall picture of the benefit of these drugs, trial authors should thus also report treatment effects on an absolute scale. Funding Acknowledgement Type of funding sources: None.