The potential of precision diabetology for type 2 diabetes treatment—evidence from a meta-regression for all-cause mortality from large cardiovascular outcome trials

AIMS: Two prerequisites must be met for the precision treatment approach to be beneficial for treated individuals. First, there must be treatment heterogeneity; second, in case of treatment heterogeneity, clinical predictors to identify people who would benefit from one treatment more than from others must be available. There is an established meta-regression approach to assess these two prerequisites that relies on measuring the variability of a clinical outcome after treatment in placebo-controlled randomised trials. We recently applied this approach to the treatment of type 2 diabetes for the clinical outcomes of glycaemic control and body weight and repeat it for the clinical outcome of all-cause mortality. METHODS: We performed a meta-regression analysis using digitalized individual participant information on time to death from 10 large cardiovascular outcome trials (7563 deaths from 99,746 participants) on DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors with respect to the variability of all-cause mortality and its potential predictors after treatment. RESULTS: The adjusted difference in log(SD) values of time to death between the verum and placebo arms was -0.036 (95%-CI: -0.059; -0.013), showing larger variability of time to death in the placebo arms. No clinical predictors were found to explain treatment heterogeneity. CONCLUSIONS: This analysis suggests that the potential of the precision treatment approach in type 2 diabetes is low, at least with regard to improvement of all-cause mortality in population with high cardiovascular risk. This extends our previous findings for the clinical outcomes of glycaemic control and body weight.