Lower liver stiffness in people with NAFLD and type 2 diabetes taking SGLT2 inhibitors and/or GLP-1 receptor agonists suggests the need for clinical trials to assess the efficacy of the agents in reducing the progression of NAFLD.
An Australian study, published in the Annals of Hepatology [link here], compared liver stiffness measurements using FibroScan in 177 patients with NAFLD and type 2 diabetes from an historical cohort (2015-2017) and 115 in a current cohort (2021-2022).
The study found SGLT2 inhibitor and GLP-1 receptor agonist use was markedly higher in the current cohort (57.4% and 42.6%) than the historical cohort (16.9% and 16.4%).
“This finding likely reflects increased provider knowledge, experience, and ease of prescribing of these medications, due to expanded indications for subsidised access under Australia’s Pharmaceutical Benefits Scheme (PBS),” the study authors said.
The first GLP-1 RA (exenatide) and SGLT2 inhibitor (canagliflozin) were listed on the PBS in 2010 and 2013 respectively.
Overall, fewer patients in the current cohort (23.9% v 38.4%; p=0.012) had LSM ≥8.0 kPa, the chosen cut-off for clinically significant fibrosis.
The study found SGLT2i and/or GLP-1 RA use was independently associated with LSM status.
Patients taking a GLP-1 RA or a SGLT2i had twice the odds of having a lower LSM (<8 kPa) compared to patients not taking these drugs (OR=2.02, 95%CI 1.05−3.86, p = 0.04 and OR 2.07 95%CI 1.04−4.10, p = 0.04, respectively).
The study said the lower LSM suggested that “in addition to cardiometabolic benefit”, GLP-1 RAs and/or SGLT2is may have an important role in reducing the risk of progression of NAFLD.
However the investigators, including Professor Elizabeth Powell from the Centre for Liver Disease Research at the University of Queensland, said the findings need to be interpreted carefully given the study design could not demonstrate causality.
They said further evidence of the antifibrotic efficacy of these agents needs to be produced in clinical trials.
The study found lower waist circumference was significantly associated with a lower LSM (<8 kPa; OR=0.95 95%CI, 0.93−0.97 p<0.01).
“Although the beneficial effects of GLP-1a and SGLT2i on steatosis and features of steatohepatitis may be largely mediated by weight loss and improved glycemic control, other indirect mechanisms of action may include anti-inflammatory effects, alterations in hepatic substrate supply and improvement in gut dysbiosis,” the authors said.