Semaglutide and tirzepatide extend GLP-1 benefits to liver health, mobility & longevity

GLP-1 medications have garnered global interest for their benefits in weight loss and diabetes management. Growing consumer access to these products is driving innovations in the food and nutrition industries for healthier, nutrient-dense options in smaller portion sizes. 

Research indicates that in the US, GLP-1 use increased 643% among adults without diabetes between 2017 and 2022. In the same time frame, medication use among patients with diabetes increased 230%. 

Concurrently, new research continuously identifies additional health benefits for GLP-1 medications, such as semaglutide and tirzepatide, beyond weight loss and diabetes management. 

Recently, scientists explored how these drugs can reduce liver scarring for people with fatty liver disease, lower the risk of knee replacement surgery for people with knee osteoarthritis, and slow biological aging in HIV patients. 

Moreover, a team at the US Mayo Clinic calls to personalize obesity treatment, using an individual’s biology instead of a one-size-fits-all approach after identifying a biological subtype of obesity that responds better to one GLP-1 medication than other patients do. 

“Because obesity increases the risk of diabetes, heart disease, certain cancers, and many other serious chronic conditions, identifying the right therapy sooner could improve long-term health outcomes,” urge the researchers.

Experts previously told Nutrition Insight that emerging science and drug product development may potentially increase the adoption of these medications even further. 

Personalized obesity treatment

The US Mayo Clinic identified a “hungry gut” obesity phenotype, which is characterized by an abnormal duration of fullness, which responds particularly well to tirzepatide. This medication mimics both GLP-1 and GIP (gastric inhibitory polypeptide), which are involved in appetite and blood sugar regulation. 

Acosta argues that obesity subtypes could guide patients toward personalized and more effective GLP-1 therapies.The team says that people with this phenotype may eat normal portion sizes but snack more frequently. Moreover, they were seen to produce lower levels of natural appetite-regulating hormones, experience faster stomach emptying, and report greater hunger after meals. 

“Obesity is a complex disease driven by different biological mechanisms,” says senior author Andres Acosta, Ph.D., a gastroenterologist and obesity researcher at the Mayo Clinic. “Our findings suggest we can begin identifying which patients are most likely to respond to specific therapies rather than treating obesity as a single disease.”

The team studied 483 adults with obesity, identifying three different biological types. They found the “hungry gut” obesity phenotype in around one in four participants, who lost an average of 21.5% of their body weight after six months of taking tirzepatide, compared to an average of 11.7% in the other groups. 

Moreover, the findings highlight that these reduced hormone levels were associated with decreased production in the intestine, instead of differences in the gut microbiome. 

The researchers caution that prospective studies are needed before an individualized approach can be incorporated into routine clinical practice, but say their findings represent an “important step” toward more precise treatment for obesity.

Liver health benefits

Additionally, US researchers at the University of California (UC) San Diego School of Medicine found that a different weight loss medication, semaglutide, may help reduce liver scarring in patients with advanced fatty liver disease, including people with early-stage cirrhosis. 

The international double-blind, randomized controlled trial included 698 adults with metabolic dysfunction–associated steatohepatitis (MASH). This is a serious form of fatty liver disease that can lead to cirrhosis, liver failure, and the need for transplantation. 

Participants received different doses of zalfermin — an experimental medicine designed to improve metabolism — with or without semaglutide, or a placebo, for one year. 

Although this combination did not outperform the placebo, semaglutide on its own showed a statistically significant improvement in liver scarring without worsening underlying liver inflammation, even among patients with the most advanced disease.

“This is the first clinical trial to demonstrate that semaglutide may improve liver fibrosis in patients with advanced MASH, including those with compensated cirrhosis,” says senior study author Rohit Loomba, M.D., a gastroenterologist and hepatologist at UC San Diego Health and chief of the Division of Gastroenterology and Hepatology at UC San Diego School of Medicine. 

Loomba notes semaglutide may improve liver fibrosis in patients with advanced MASH.“The results with semaglutide alone are encouraging and suggest a potential new treatment option for a group of patients who previously had very few.”

Meanwhile, the researchers note that larger clinical trials are needed that focus on patients with cirrhosis to confirm these results. 

“These findings strengthen the need to continue studying semaglutide and other metabolic therapies in advanced liver disease,” says Loomba. “Our goal is to move the field toward effective, accessible treatments that can slow or even reverse liver damage before patients reach liver failure.”

Mobility support

Joint health and mobility are key aspects of healthy aging, where ingredients such as collagen, vitamin K2, and chondroitin sulfate are driving innovation in nutrition and supplements. 

In this space, research also highlights potential benefits for GLP-1s, linking the medications to a significantly lower long-term risk of knee replacement surgery as a result of osteoarthritis. The analysis of medical records data found the greatest effects for sustained use of newer semaglutide and tirzepatide medications. 

The WHO estimates that around 365 million people globally suffer from knee osteoarthritis, where the protective cartilage that cushions the ends of the bones wears down, which can result in requiring knee replacement surgery. 

The researchers note that there is no medication that can modify the disease, where staying active and maintaining a healthy weight can help slow disease progression. 

Using data from the TriNetX Global Research Network, they grouped almost 115,000 patients with knee osteoarthritis around the type of GLP-1 medication received and duration, one or three years. They balanced the groups for age, sex, race, musculoskeletal diagnoses, obesity-related conditions, body mass index, and proxies for health care access. 

Additionally, the researchers identified the need for knee replacement surgery at years one, three, five, and eight after diagnosis. 

Using semaglutide or tirzepatide for three years resulted in a 4.71 percentage point lower risk of needing knee surgery at eight years. 

Corley sees semaglutide slowing biological aging markers in adults with HIV.Although prospective trials are needed to establish causality, the researchers note that the identified associations could shift treatment paradigms toward “integrating metabolic health as a core component of joint preservation and inform guidelines on GLP-1 use in patients at risk of surgical progression.”

GLP-1s for longevity

Another recent study at UC San Diego indicates healthy aging benefits for GLP-1s, an area that is also driving nutrition innovations as consumers seek to extend their healthspan. 

The randomized, placebo-controlled trial found that semaglutide slows the accumulation of biological aging markers in the DNA of adults with HIV. Researchers at the university and partner institutions analyzed data from an earlier trial with 108 adults with HIV-associated lipohypertrophy, a condition where excess fat builds up around the abdomen. 

Around half of these participants received semaglutide injections, with the rest receiving placebo shots, over 32 weeks. The researchers tracked cellular aging through epigenetic clocks that detect DNA methylation. 

Although HIV patients often experienced accelerated aging, the trial showed that semaglutide slowed the pace of biological aging by 9% according to one of the epigenetic clocks used. 

Participants taking this medication exhibited a broad pattern of slower biological aging across epigenetic clocks linked to inflammation and blood, brain, heart, kidney, liver, and metabolic health.

Moreover, a different clock indicated that semaglutide slowed biological processes associated with the risk of all-cause mortality and age-related disease. 

“We are not saying that semaglutide reverses aging or makes people younger,” said the study’s first author, Michael Corley, Ph.D., associate professor at UC San Diego School of Medicine. 

“What we are seeing is a signal that it may slow some of the biological processes associated with aging. With newer GLP-1–based therapies now emerging, the field has an opportunity to test whether different drugs in this class have distinct effects on aging biology and to identify which patients may benefit most.”