Assessing the Potential for Precision Medicine in Body Weight Reduction with Regard to Type 2 Diabetes Mellitus Therapies: A Meta-regression Analysis of 120 Randomized Controlled Trials

Aims: To assess the potential for precision medicine in type 2 diabetes by quantifying the variability of body weight as response to pharmacological treatment and to identify predictors which could explain this variability.

Methods: We used randomized clinical trials (RCTs) comparing glucose-lowering drugs (including but not limited to sodium-glucose cotransporter-2 inhibitors, glucagon-like peptide-1 receptor agonists and thiazolidinediones) to placebo from four recent systematic reviews. RCTs reporting on body weight after treatment to allow for calculation of its logarithmic standard deviation (log[SD], i.e., treatment response heterogeneity) in verum (i.e., treatment) and placebo groups were included. Meta-regression analyses were performed with respect to variability of body weight after treatment and potential predictors.

Results: A total of 120 RCTs with a total of 43 663 participants were analysed. A slightly larger treatment response heterogeneity was shown in the verum groups, with a median log(SD) of 2.83 compared to 2.79 from placebo. After full adjustment in the meta-regression model, the difference in body weight log(SD) was -0.026 (95% confidence interval -0.044; 0.008), with greater variability in the placebo groups. Scatterplots did not show any slope divergence (i.e., interaction) between clinical predictors and the respective treatment (verum or placebo).

Conclusions: We found no major treatment response heterogeneity in RCTs of glucose-lowering drugs for body weight reduction in type 2 diabetes. The precision medicine approach may thus be of limited value in this setting.