Several metabolic abnormalities and cardiorenal outcomes have shown an association with elevated liver function tests (LFT). The abstract presented reported the outcome of the analysis studying the association between LFT levels within the accepted range and cardiorenal outcomes in patients with type 2 diabetes. In addition, the effect of canagliflozin treatment versus placebo was observed.

For the analysis, serum alanine aminotransferase (ALT), aspartic aminotransferase (AST), gamma-glutamyl transferase (γGT), alkaline phosphatase (ALP), and bilirubin concentrations of 10,142 patients were recorded at baseline and during follow-up. The association between LFTs to the cardiorenal outcomes such as first hospitalized heart failure (HHF), cardiovascular (CV) and all-cause mortality, and progression of renal impairment was assessed by the multivariate proportional-hazards models. The univariate analysis demonstrated that ALT was reciprocally predictive, and ALP was positively predictive of all adjudicated outcomes.  ɣGT had a direct relationship with cardiovascular outcomes but not with renal outcomes.  In mutivariate models including all 5 LFTs and 19 potential clinical confounders, revealed an independent association between ALT and lower CV outcome risk while ɣGT was associated with higher CV outcome risk. Canagliflozin treatment was associated with significantly reduced ALT, AST, and γGT over time. In a fully adjusted model including updated LFT levels and treatment, γGT was independently associated with CV and all-cause mortality, ALP with renal dysfunction progression, canagliflozin treatment with a significant reduction in HHF and renal risk.

The above results infer that among the LFT markers, higher ɣGT are indicative of the risk of HHF and death in patients with T2DM and high CV risk while ALT levels have a protective effect. Canagliflozin reduces the risk of HHF and renal damage irrespective of LFTs and potential confounders.