Lower prevalence of elevated liver stiffness measurements in people with type 2 diabetes taking sodium-glucose co-transporter 2 inhibitors or glucagon-like peptide-1 receptor agonists

Abstract

Introduction and Objectives: Among people with type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD) is very common and has an increased risk of clinically significant liver disease. The use of sodium-glucose co-transporter 2 (SGLT2i) inhibitors and glucagon-like peptide-1 (GLP-1a) receptor agonists is endorsed to reduce major cardiovascular events and/or progression of chronic kidney disease. Their prevalence of use in people with T2D and co-existent NAFLD remains unclear. We sought to determine the prevalence of use of these medications at two different time periods, and their association with prevalence of clinically significant liver disease. Materials and Methods: Consecutive people with type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) were recruited from diabetes clinics between Jun-2021 and Jun-2022 (‘current’ cohort). Liver stiffness measurements (LSM) using FibroScan were performed. Medication data were collected prospectively at recruitment and verified with the dispensing pharmacy or general practitioner medical records. Data for a historical cohort with NAFLD and T2D recruited from the same clinics during 2015–2017 (‘historical’ cohort) were available. Logistic regression was used to evaluate factors associated with LSM <8.0 or ≥8 kPa (clinically significant fibrosis). Results: There were 292 participants, 177 in the historical cohort and 115 in the current cohort. In the current cohort, 57.4% of patients with T2D and NAFLD were taking a GLP-1a and 42.6% were taking a SGLT2i; a 2.6 to 3.4-fold higher prevalence than in 2015–2017. A lower proportion of the current cohort (23.9% compared to 38.4%) had clinically significant fibrosis (LSM ≥8 kPa; p = 0.012). When the cohorts were pooled and differences adjusted for in multivariable logistic regression analysis, patients taking a GLP-1a or a SGLT2i were 2 times more likely to have a lower LSM (<8 kPa) compared to patients not taking these drugs (OR=2.05, 95%CI 1.07–3.94, p = 0.03 and OR 2.07 95%CI 1.04–4.11, p = 0.04, respectively). Conclusions: The observation of a lower LSM in people taking SGLT2i and/or GLP-1a following adjustment for other relevant clinico-demographic variables provides support for clinical trials to assess their efficacy in reducing the progression of NAFLD.

Keywords

• Non-alcoholic fatty liver disease
• Diabetes mellitus, type 2
• Sodium-glucose transporter 2 inhibitors
• Hypoglycemic Agents
• Glucagon-Like Peptide-1 Receptor
• Elasticity Imaging Techniques