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Purpose Diabetic kidney disease affects nearly one-third of US adults with prevalent type 2 diabetes mellitus. The use of new antidiabetic medications in the prevention and treatment of diabetic kidney disease is a growing area of research interest. 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 seven eligible studies for analysis. Included studies were published between 01/2013-03/2020, conducted among adults, in English full-text, 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, HbA1c, and mean duration of T2DM at baseline. Main Conclusions Compared to 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.

BACKGROUND:Oral semaglutide is the first oral formulation of a glucagon-like peptide 1 (GLP-1) receptor agonist to be approved in the United States for glycemic control in people with type 2 diabetes mellitus (T2DM).While oral semaglutide is not indicated for reduction of cardiovascular event risk, its label does include evidence of no increase in cardiovascular risk in people who received oral semaglutide.

The risk of composite outcome was significantly lower among SGLT2 inhibitor therapy users compared to IBT users (Hazard ratio (HR):0.778, p=0.001, 95% confidence interval (CI):0.671-0.904). When individual outcomes were considered SGLT2 inhibitor users had a lower risk of stroke (HR:0.831, p=0.028, 95%CI:0.704-0.981) and MI (HR:0.704, p=0.024, 95%CI:0.519-0.955) compared to IBT users. However, the difference in the risk of all-cause mortality was non-significant between two groups (HR:1.605, p=0.433, 95%CI:0.492-5.238). Among patients with co-morbid HF, the risk of HF-related ER visits was significantly lower for SGLT2 inhibitor therapy users (HR:0.629, p,0.001, 95% CI:0.507-0.779) compared to IBT users, but the association was not significant for HF-related hospitalizations (HR:0.770, p=0.109, 95%CI:0.560-1.060). Conclusions: SGLT2 inhibitor therapy use was associated with a lower risk of stroke, MI, and HF-related ER visits compared to IBT use.

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