By Elaine Chen 
STAT - Reporting from the frontiers of health and medicine

Liver illustration
HYACINTH EMPINADO/STAT
SAN DIEGO — The American Diabetes Association said Sunday that all adults with type 2 diabetes or prediabetes should be screened for nonalcoholic fatty liver disease, an increasingly prevalent condition that can lead to serious liver damage.

There are no approved medications for the disease, but among available diabetes drugs, the ADA singled out GLP-1 treatments as an option doctors could consider, according to recommendations published during the annual ADA conference.
GLP-1 treatments, such as Ozempic and Mounjaro, are a class of drugs that have grown widely popular for their efficacy not only in lowering blood sugar, but also cutting weight. Drugmakers have started to study them in liver disease, and while some trials have shown they may offer some benefits, they haven’t yet been shown to improve harmful liver scarring.

The ADA published recommendations on the disease because “we realized this is just becoming such a pervasive issue,” said Robert Gabbay, the ADA’s chief science and medical officer. “In many ways, type 2 diabetes and obesity are becoming the leading causes of liver disease, and that’s not really on the radar of people thinking about diabetes.”
Nonalcoholic fatty liver disease, which occurs when excess fat builds up in the liver, is estimated to affect about 24% of U.S. adults. A rarer, severe form called nonalcoholic steatohepatitis, or NASH, in which there’s inflammation and scarring of the liver, has grown into one of the leading causes of liver transplantation and liver cancer.
Though the condition is growing in prevalence, there haven’t been any drugs approved to treat it. Just this past week, the Food and Drug Administration rejected a NASH treatment from Intercept Pharmaceuticals after advisers to the agency raised safety concerns.

In the new recommendations, the ADA said all diabetes patients should be screened with what’s known as a fibrosis-4 index, which is calculated based on age and standard blood measures of ALT, AST, and platelet count.

People with a high index should undergo further tests like liver stiffness measurement or the enhanced liver fibrosis test. If they’re determined to be at high risk for liver scarring called fibrosis, they should be referred to a gastroenterologist or hepatologist, the ADA said.

Once patients are diagnosed with the disease, doctors should recommend patients lose weight through lifestyle changes and consider prescribing a GLP-1 drug, the ADA said. The group also suggested pioglitazone, an older diabetes medication that some studies showed may help with aspects of the disease.

While other diabetes drugs may continue to be used to lower blood sugar, there’s a lack of evidence they help with fatty liver disease, the ADA said.

There’s also still limited data on the efficacy of GLP-1s in fatty liver disease. One trial of semaglutide, the active ingredient in Ozempic, showed the drug was linked to a higher rate of NASH resolution but didn’t significantly improve liver scarring — a key factor regulators consider when reviewing drugs for the liver disease.
There are also other drugs in the pipeline for NASH that may prove more effective than GLP-1s. A recent small study found that an experimental drug from Akero Therapeutics combined with a GLP-1 led to reduced liver fat and improved markers of liver scarring compared with just a GLP-1 alone.

However, newer versions of GLP-1 drugs in development may be more promising against fatty liver disease. Merck presented data this week showing that its experimental drug — which targets not only the GLP-1 hormone, but also the glucagon hormone — led to greater reduction in liver fat compared with semaglutide. Boehringer Ingelheim is also testing a drug that targets GLP-1 and glucagon in NASH patients.