ADA 2026: Survodutide Cuts Visceral Fat and Normalizes Liver Fat in MASLD. Here's What the Data Mean for Metabolic Risk

For patients living with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD), 2 questions have dominated clinical conversations around newer glucagon-like peptide-1 (GLP-1)–based therapies: what exactly is being lost during weight loss, and can these treatments do more than reduce the number on a scale? Data from the SYNCHRONIZE program, presented at the American Diabetes Association (ADA) 2026 Scientific Sessions, are beginning to provide answers.

The SYNCHRONIZE-1 sub-study found that survodutide, a dual glucagon/GLP-1 receptor agonist, drove tissue loss that was predominantly fat rather than lean mass, with lean mass loss in the 10% to 11% range, well below the 50% threshold seen with some other approaches. Separately, the SYNCHRONIZE-MASLD study found that 6 out of 10 patients treated with survodutide achieved full liver fat normalization at 48 weeks, a result with meaningful implications for halting disease progression to metabolic dysfunction-associated steatohepatitis (MASH).

In this interview, Lee Kaplan, MD, PhD, explains why the preferential loss of visceral fat matters beyond the liver, why lean mass preservation may be especially important in older patients, and why normalizing liver fat—not just reducing it—represents the highest-value clinical target in MASLD management.

Q: The SYNCHRONIZE-1 sub-study showed that visceral fat, not lean mass, accounted for the majority of tissue loss with survodutide. Why does that distinction matter clinically, and what does losing visceral fat specifically mean for a patient’s long-term metabolic risk?

Lee Kaplan, MD, PhD: There are 2 questions in there that I think need to be separated. First of all, the majority of tissue loss for any of the current modern treatments of obesity is loss of fat. There is no mechanism of weight loss that is primarily muscle, so we’re just talking about amounts. As it turns out, survodutide is associated—as we saw in the studies reported at ADA—with less lean mass loss. Lean mass includes not only muscle, but organ mass as well, and in some cases, bone mass. There’s less of that loss observed after treatment with survodutide, but in all cases it’s less than 50%; in the case of survodutide, it’s in the 10 to 11% range. Having said that, what the benefit of that is is yet to be determined. We know that people who are older, and there are a number of diseases associated with what’s called sarcopenia—which is an inadequate amount of muscle mass—obviously want to preserve muscle mass. For otherwise normal patients who have obesity, the loss of muscle mass is probably reasonably tolerated, because people with obesity tend to have more muscle mass from carrying more weight, and that builds muscle to an extent. Now let’s turn to the issue of visceral fat loss. Visceral fat is a small part of the fat in the body—only one to two kilograms, even in somebody who might weigh 100 kilograms overall—but it’s a critical depot of fat because the presence of excess visceral fat, in and around the organs in the abdomen, is associated with inflammatory complications, immune complications, and inflammation in the fat itself that’s associated with a whole variety of metabolic diseases and complications. The improvement from decreasing visceral fat with survodutide is a demonstrably important observation, because it suggests that not just liver disease will improve, but that other metabolic complications and other autoimmune and inflammatory complications of obesity are also likely to improve. Future studies are going to be necessary to show the extent of that improvement, but as a first step, it’s a very important and very optimistic one.

Q: In SYNCHRONIZE-MASLD, 6 out of 10 patients treated with survodutide achieved liver fat normalization at 48 weeks. How significant if that outcome for patients with MASLD, and does reducing liver fat at this level translate into meaningful protection against disease progression to MASH?

Kaplan: This is a critically important question. That degree of decrease in liver fat has been shown in numerous studies to be associated with a decreased risk of conversion from MASLD without MASH—meaning without the autohepatitis, without the inflammation and liver cell damage, without the fibrosis—to MASH, which then leads to those complications. As far as preventing progression, these data are very supportive of the idea that we can prevent it. The patients in the SYNCHRONIZE-MASLD study were patients who primarily had MASH. They weren’t biopsied in order to prove it—that wasn’t the design of the study—but all of the non-invasive indicators that can be used by any clinician, any primary care clinician, or other prescriber, or someone who manages the patient, even beyond just being a liver specialist, can use those noninvasive tests to assess whether somebody has evidence of MASH. In that case, the patients who participated in the SYNCHRONIZE-MASLD study all had evidence of MASH. Now, what this decrease in liver fat demonstrates is the ability to actually effectively treat MASH. MASH has multiple components: it has damage to the liver, it has inflammation, and it can lead to fibrosis—and all of those have been shown in previous studies to be improved by decreasing liver fat to a certain extent. Normalizing liver fat is, of course, the best outcome, because then you’re eliminating the excess fat in the liver entirely, and that is associated with the best response to all of these components of the disease that we call MASH.