Effects of antidiabetic agents on steatosis and fibrosis biomarkers in type 2 diabetes: A real‐world data analysis

Abstract

Background & Aims There is intense research for drugs able to reduce disease progression in nonalcoholic fatty liver disease. We aimed to test the impact of novel antidiabetic drugs (dipeptidyl‐peptidase‐4 inhibitors – DPP‐4Is, glucagon‐like peptide‐1 receptor agonists – GLP‐1RAs, sodium‐glucose cotransporter‐2 inhibitors – SGLT‐2Is) on non‐invasive biomarkers of steatosis (fatty liver index, FLI) and fibrosis (Fibrosis‐4 score, FIB‐4) in patients with type 2 diabetes (T2D). Methods Clinical, anthropometric and biochemical parameters were retrospectively analysed in 637 consecutive T2D patients switched from metformin w/wo sulfonylureas and/or pioglitazone to DPP‐4Is, GLP‐1RAs and SGLT‐2Is in a tertiary care setting. 165 patients maintained on original treatments served as controls. The effects on FLI and FIB‐4 at 6‐ and 12‐month follow‐up were analysed by logistic regression after adjustment for baseline differences, computed by propensity scores, and additional adjustment for changes in glycosylated hemoglobin (HbA1c) and body mass index. Results Body mass index, HbA1c and aminotrasferases significantly decreased following switching to GLP‐1RAs and SGLT2‐Is, compared with both controls and DPP‐4Is, whereas only HbA1c was reduced on DPP‐4Is. FLI and FIB‐4 were reduced on GLP‐1RA and SGLT‐2I; logistic regression analysis confirmed a significant improvement of both biomarkers after adjustment for propensity score. The shift of FIB‐4 values towards the category ruling out advanced fibrosis was maintained after additional adjustment for confounders. These effects were confirmed in a sensitivity analysis on effect size. Conclusions Glucagon‐like peptide‐1 receptor agonists and SGLT‐2Is improve biomarkers of steatosis and fibrosis, in keeping with beneficial effects on liver disease progression, and should be considered the treatment of choice in T2D.

Effects of empagliflozin on markers of liver steatosis and fibrosis and their relationship to cardiorenal outcomes

“…However, a recent post‐hoc analysis of DURATION‐8 reported a small decrease in the proportions of participants at high risk for fibrosis by NFS and FIB‐4 from baseline to 28 weeks in individuals with type 2 diabetes 17 . Furthermore, a real‐word data analysis from people with type 2 diabetes who switched to sodium glucose co‐transporter 2 inhibitor treatment also found the number of cases classified as advanced fibrosis by FIB‐4 reduced after 6 and 12 months 18 . At least in part, discrepancies in the different studies may be because of cohort characteristics.…”

Association between use of liraglutide and liver fibrosis in patients with type 2 diabetes

“…Nevertheless, the study failed to show any significant improvement in fibrosis stage ( 18 ). In another real-world study, GLP-1RAs use was shown to improve markers of liver fibrosis in T2DM ( 21 ). Consistently, we observed decreased prevalence of advance liver fibrosis in T2DM individuals treated with liraglutide compared with nousers.…”

Clinical Nutrition: Recent Advances and Remaining Challenges

“…Sarcopenia-accelerated by upregulation of myostatin due to hyperammonaemia-becomes a predictor of morbidity and mortality, aggravated by obesity (sarcopenic obesity) [185,186], and is difficult to treat. Bariatric surgery is frequently contraindicated [187]; also pharmacologic treatment with GLP-1 agonists favouring weight loss [188], such as liraglutide, may be contraindicated by the presence of varices at risk of bleeding [189], and dietary treatment remains the sole possibility.…”

“…Data on zinc supplementation is conflicting: some studies report positive effects on zinc supplementation in hepatic encephalopathy [180][181][182], while others report no significant improvements [183,184]. Zinc supplementation in case of deficiency improves liver function and nutritional status [185,186] and may even impact positively on clinical outcome [187,188]. Normalizing zinc and vitamin A levels can also indirectly improve the nutritional status by a positive effect on sense of taste and thereby increased food intake [94,189].…”