Letter by Xie et al Regarding Article, "Effects of Liraglutide Versus Placebo on Cardiovascular Events in Patients With Type 2 Diabetes Mellitus and Chronic Kidney Disease: Results From the LEADER Trial".

May 28, 2019 e1015 Jian Xie, MD Mingyang Jiang, MD Lang Li, MD, PhD To the Editor: We read with interest the study from Mann et al1, wherein the authors performed a large randomized, controlled trial to assess the effects of liraglutide versus placebo on cardiovascular events in patients with type 2 diabetes mellitus and chronic kidney disease (CKD). They concluded that liraglutide added to standard of care reduced the risk for major cardiovascular events and all-cause mortality in patients with type 2 diabetes mellitus and CKD. After a careful review, we have the following suggestions. First, in the clinical standards, CKD was divided into 5 stages according to the estimated glomerular filtration rate (eGFR) level.2 In stage 1, eGFR was normal or slightly increased; in stage 2, eGFR was between 60 to 89 mL/min per 1.73 m2; in stage 3, eGFR was between 30 to 59 mL/min per 1.73 m2; in stage 4, eGFR was between 15 to 29 mL/min per 1.73 m2; and in stage 5, eGFR was less than 15 mL/min per 1.73 m2. This CKD staging, shown in Figure 2, is different from what is commonly used clinically, and may affect the persuasiveness of this study. We would like the author to describe the source and reason for the use of the staging criteria in this study. Second, the number of patients with severe hypoglycemia with eGFR <60 mL/ min per 1.73 m2 was significantly less than those with eGFR ≥60 mL/min per 1.73 m2. Therefore, the benefits were likely to materialize after the use of liraglutide in the eGFR <60 mL/min per 1.73 m2 group. The author concluded that for all components of the primary and expanded composite cardiovascular outcome, and for all-cause death, the estimated treatment effect of liraglutide was increased in those with eGFR <60 mL/min per 1.73 m2. We doubt whether this conclusion would still be valid when the number of patients with severe hypoglycemia with eGFR <60 mL/min per 1.73 m2 increased to the same level as the eGFR ≥60 mL/min per 1.73 m2 group. Moreover, the proportion of the different race groups was unbalanced. Economic and social factors would lead to inadequate data of nonwhite individuals. However, the tolerance varies from race to race. When black, Asian, and other races increase in number, the results could inevitably be affected. Therefore, we recommend that the author consider racial differences in the subgroup analysis. Third, in the Outcome section, the body weight was included as one of the secondary outcomes from baseline to 36 months. As opposed to body weight, body mass index is a more internationally recognized health indicator, which better reflects the human body size.3 The results would be more persuasive if the authors used body mass index instead of weight as a secondary outcome. Finally, in Figure 1, we observed that only a small number of the results in the eGFR <60 mL/min per 1.73 m2 group or micro/macroalbuminuria group were beneficial, but the author concluded that “Liraglutide added to standard of care reduced the risk for major cardiovascular events and all-cause mortality in patients with T2D and CKD. These results appear to apply across the CKD spectrum © 2019 American Heart Association, Inc. LETTER TO THE EDITOR