NASH in diabetes – a therapeutic opportunity?

Given the inexorable ties of NAFLD to obesity and insulin resistance, the prevalence of NAFLD is 2 to 3 times more common in patients with type 2 diabetes mellitus (T2DM) compared to the general population. In a recent prospective study, Harrison and colleagues enrolled a middle-aged U.S. cohort undergoing screening colonoscopy for concomitant evaluation for the presence of NAFLD and NASH. In their cohort, the subset of the population with T2DM had an astonishing prevalence of NAFLD at 70% and NASH at 35%. Unfortunately, the vast majority of patients with T2DM afflicted by NAFLD remain undiagnosed. Therefore, recent guidelines from the American Diabetes Association (ADA) and the American Association of Clinical Endocrinology (AACE) strongly recommend NAFLD screening in patients with obesity and T2DM. At the recent annual meeting of the American Association for the Study of Liver Diseases (AASLD), Ajmera and colleagues presented their results of 493 prospectively recruited middle-aged (≥ 50 years) patients with T2DM, after the exclusion of other causes of liver disease. The subjects underwent Fibroscan® and/or MR imaging to identify those with advanced fibrosis. While 14% of these patients had evidence of advanced fibrosis, 5.9% had evidence of cirrhosis. Alarmingly, three patients with cirrhosis were found to have incidental hepatobiliary cancer.

One possible explanation of why NAFLD remains undiagnosed in the vast majority of the afflicted population may be the lack of a licensed treatment for NASH, leading to the perception that lifestyle modification is the only available option for managing these patients. The recent AACE guidelines aim to address this issue by recommending the following: “clinicians must consider treating diabetes with pioglitazone and/or GLP-1 RAs when there is an elevated probability of having NASH based on elevated plasma aminotransferase levels and non-invasive tests”.  These guidelines highlight the currently available evidence that both pioglitazone and investigated GLP-1 RAs (liraglutide and semaglutide) were superior to placebo for the endpoint of NASH resolution. Furthermore, in small single-center and multi-center studies, pioglitazone improved the mean fibrosis score suggesting a weak antifibrotic effect. The authors also point out preliminary evidence from SGLT-2 inhibitors that have shown decreased liver fat with this class of medications; however, supporting evidence of histological improvement is awaited.

- Dr. Prashant Pandya

Highlighted Article

With this in mind, I would like to highlight a recent presentation at this year’s American College of Gastroenterology meeting. Eltelbany and colleagues from the Cleveland Clinic conducted a retrospective population health study using an extensive inpatient and outpatient database covering 74 million patients from over 300 U.S. hospital systems. This study compared cirrhosis prevalence in two groups of patients with T2DM and NASH — those who received either a GLP-1 RA or SGLT-2 drug with those not treated with either drug class. Their findings revealed a potentially beneficial effect of these treatments in reducing the risk of cirrhosis. While far from definitive, these findings add credence to AACE guidelines that promote the use of specific antidiabetic agents to potentially slow down the progression of NASH in patients with T2DM.