Microvascular Benefits of New Antidiabetic Agents: A Systematic Review and Network Meta-Analysis of Kidney Outcomes

Abstract

Context: Diabetic kidney disease affects nearly one-third of US adults with prevalent type 2 diabetes mellitus (T2DM). The use of new antidiabetic medications in the prevention and treatment of diabetic kidney disease is a growing area of research interest. Objective: We sought to characterize the risk of developing a composite kidney outcome among patients receiving a new antidiabetic medication of the SGLT-2i, GLP-1ra, and DPP-4i drug classes. Methods: We conducted a systematic literature search in MEDLINE to identify randomized trials observing kidney safety endpoints associated with the use of new antidiabetic medications. Two independent reviewers selected the 7 eligible studies for analysis. Included studies were published between January 2013 and March 2020, conducted with adult participantss, published full-text in English, and observed composite kidney outcomes. A network meta-analysis was conducted within a Bayesian framework using a fixed-effects model with uninformative priors. Results: A qualitative assessment of transitivity was conducted to ensure similar distribution of potential modifiers across studies. Included studies were generally comparable in mean age, glycated hemoglobin A1c (HbA1c), and mean duration of T2DM at baseline. Main Conclusions: Compared with placebo, dapagliflozin was associated with the greatest reduction in risk of developing the composite kidney outcome (hazard ratio 0.53; 95% credible interval, 0.43-0.66) followed by empagliflozin, canagliflozin, semaglutide, and liraglutide. Linagliptin did not show a significant reduction in risk of the outcome. Limitations: This analysis was limited by the scarcity of data for kidney safety endpoints in large, randomized clinical trials. Although the heterogeneity statistic was low, there are slight differences in study design and baseline demographic characteristics across trials.