ADA Issues New MASLD Guidelines

Medscape

2 days ago

A new consensus report from the American Diabetes Association (ADA) provides a practice-oriented framework for screening and managing metabolic dysfunction–associated steatotic liver disease (MASLD) in people with diabetes and prediabetes.
Published online on May 28, 2025, in Diabetes Care, the report is a comprehensive update to the recommendations the ADA released in 2023. It is intended for clinicians treating patients with diabetes — primarily type 2 diabetes (T2D) — but also type 1 diabetes with obesity and prediabetes. Topics covered include the rationale for the recent change in terminology, epidemiology, fibrosis risk stratification, monitoring, treatment, and referral guidance, with interprofessional team management emphasized throughout.
'This will provide primary care doctors and anyone taking care of people with diabetes the tools to diagnose [MASLD] early and guide therapy…to prevent cirrhosis, and refer to the hepatologist as needed for additional therapy and monitoring,' lead author Kenneth Cusi, MD, professor of medicine at the Division of Endocrinology, Diabetes & Metabolism in the Department of Medicine at the University of Florida, Gainesville, Florida, told Medscape Medical News .
The guidelines recommend that clinicians routinely screen people with T2D or prediabetes for MASLD. 'We explain that the liver should be incorporated into our management in the same way we do for chronic kidney disease, eye disease, and nerve disease as an end-organ damage that is particularly affected by diabetes,' Cusi said.
In the United States, at least 70% of people with T2D have MASLD, about half of whom have the more progressive form termed metabolic dysfunction–associated steatohepatitis (MASH). About 1 in 5 with T2D have advanced liver fibrosis. The presence of MASH increases the risks for complications including cirrhosis, hepatocellular carcinoma, and overall mortality, according to the new consensus report.
Liver disease has not been a focus of diabetes management until recently, Cusi noted. 'We didn't think about it. The epidemic of obesity, and with that, of diabetes, is driving this liver disease. The obesity epidemic has had a big worsening since the 1990s, so this damage in the past 20 or 30 years is just now becoming evident in the liver.'
Terminology Change: Highlighting Insulin Resistance, Reducing Stigma
The document reviews the current nomenclature for SLD, which was officially changed in 2023 to remove the words 'fatty' and 'alcoholic.' Now, MASLD is defined as the presence of SLD with at least one metabolic risk factor such as obesity, hypertension, prediabetes, high triglycerides, low high-density lipoprotein cholesterol, or T2D, with minimal or no alcohol consumption (< 20 g/d for women; < 30 g/d for men).
The term 'MetALD' is used for those with MASLD who also have increased alcohol consumption (20-50 g/d for women; 30-60 g/day for men). Steatosis in the setting of alcohol consumption above those levels is termed 'alcohol-associated liver disease (ALD).'
The term MASH is defined as steatohepatitis with at least one metabolic risk factor and minimal alcohol consumption. 'At-risk MASH' refers to steatohepatitis with clinically significant fibrosis (stage F2 or higher).
Diagnosis: Staged Screening for Fibrosis
The document recommends routine screening of people with T2D, prediabetes, and/or obesity with cardiovascular risk factors, with the goal of identifying those with high-risk MASH. Intervention is then aimed at preventing fibrosis progression and cirrhosis.
A graphic diagnostic algorithm advises initial use of the noninvasive Fibrosis-4 (FIB-4) tool, which risk stratifies based on age, liver enzymes, and platelet count.
'The FIB-4 is composed of very simple things that are already in the electronic medical record of all patients. We also discuss the role of electronic medical records to improve implementation,' Cusi said.
Those with a FIB-4 < 1.3 have a low risk for future cirrhosis and can be managed in primary or team care with optimized lifestyle and repeated FIB-4 every 1-2 years.
If the FIB-4 is > 2.67, direct referral to a liver specialist is advised. If FIB-4 is between 1.3 and 2.67, a second risk-stratification test is recommended. Ideally, this would be a liver stiffness measurement (LSM), most commonly with transient elastography. If that is unavailable, an alternative is the noninvasive enhanced liver fibrosis (ELF) test.
If the LSM is < 8.0 kPa or ELF is < 7.7, the fibrosis risk is low and routine management can continue with repeat testing in 1-2 years. But if higher, hepatology referral is recommended.
Treatment: Lifestyle, Plus Old and New Drugs
The report details lifestyle modification for MASLD, including nutrition plans; physical activity; behavioral health; and the role of diabetes self-management, education and support. The role of obesity treatment in people with MASLD, both metabolic surgery and pharmacotherapy, is also discussed at length.
No current pharmacologic treatments have been approved for MASLD, but both semaglutide and tirzepatide have demonstrated benefit in treating MASH and are approved for treating T2D, obesity, and other related comorbidities.
A thyroid hormone receptor beta agonist, resmetirom, was approved in early 2024 for the treatment of MASH with fibrosis stages F2 and F3, but is extremely expensive at about $50,000 a year, Cusi noted. An older, generic glucose-lowering drug, pioglitazone, has also shown benefit in reducing fibrosis and may be a lower-cost alternative.
The document also includes a section on alcohol intake, which complicates the MASLD picture, Cusi noted. 'We think that this is going to help doctors to consider alcohol, which is often overlooked and under-reported. If patients have moderate fibrosis, they should completely quit alcohol.'
Cusi has received research support (to his institution) from Boehringer Ingelheim, Echosens, Inventiva, Labcorp, and Perspectum, and has served as a consultant for Aligos Therapeutics, Arrowhead, AstraZeneca, 89bio, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Novo Nordisk, ProSciento, Sagimet Biosciences, Siemens USA, Zealand Pharma, and Terns Pharmaceuticals.