GLP-1 drugs such as semaglutide may slow the rate at which the body ages at a cellular level, the first randomised, placebo-controlled clinical evidence suggests.
The study, published in Nature Communications by researchers at the University of California, San Diego (UC San Diego), examined 108 adults living with HIV who had lipohypertrophy – a condition involving excess fat accumulation that is common in people receiving injections and is associated with accelerated ageing. A smaller pilot group also included individuals with metabolic dysfunction-associated steatotic liver disease (MASLD).
Using “epigenetic clocks” to analyse DNA methylation patterns – chemical modifications that influence gene activity without altering the genetic code – the team found that participants treated with semaglutide showed a slower progression of several markers linked to biological ageing compared with those given a placebo. The DunedinPACE clock, which measures the pace of ageing, recorded a 9% reduction in the speed of biological ageing among those taking the drug. Another measure, the PCGrimAge clock, which tracks markers tied to all-cause mortality risk and age-related disease, also showed significant improvements. In the pilot group of patients with HIV and MASLD, semaglutide reduced the pace of biological ageing in 42% of participants and slowed ageing-related mortality-risk markers in 34%.
“We are not saying that semaglutide reverses ageing or makes people younger,” said Michael Corley, an associate professor of medicine at UC San Diego. “What we are seeing is a signal that it may slow some of the biological processes associated with ageing.”
What are GLP-1 drugs?
GLP-1 receptor agonists, including semaglutide – sold under brand names such as Ozempic and Wegovy – mimic a natural hormone that regulates appetite, slows gastric emptying and improves insulin sensitivity. They are widely prescribed for weight loss, type 2 diabetes and cardiovascular disease. Around 30 million Americans are currently taking these medications.
The new findings build on a growing body of evidence that the drugs may offer benefits beyond metabolic control. Past research from the University of Colorado at Boulder Anschutz has shown that GLP-1s may reprogramme cells to boost the body’s immune response, and the UC San Diego team believes similar mechanisms could be at work in this study. “Emerging data also suggest that GLP-1 drugs may reprogram certain cells in different organs,” Corley said.
How do GLP-1 drugs reduce inflammation and boost immune health?
The central explanation proposed by researchers revolves around the drugs’ ability to reduce chronic inflammation, a key driver of accelerated ageing. Inflammation is the body’s natural response to injury or infection, but when it persists it can damage organs, tissues and accelerate cell ageing. GLP-1 drugs help patients shed excess fat, particularly visceral fat – the metabolically active fat around internal organs that produces inflammatory signals. By reducing this fat, the drugs quieten chronic immune activation and lower the production of inflammatory cytokines.
Improved insulin sensitivity and stable blood sugar levels also reduce oxidative stress, which can otherwise promote inflammatory responses. In people living with HIV, who often experience heightened chronic immune activation, these effects may be especially pronounced. “Many of the biological processes we study in HIV are also central to ageing in the general population,” Corley noted. “Because these processes can emerge earlier or be more pronounced in people with HIV, this community can help us identify interventions that may improve healthspan more broadly.”
The study found that improvements in ageing-related measures were observed across multiple organ systems, including the blood, brain, heart, liver, kidneys and metabolic health, suggesting broad systemic effects. The researchers also noted that inflammation raises the risk of developing chronic diseases, including HIV – previous research has shown that women with genital inflammation are at increased risk of sexual HIV infection. By curbing inflammation, GLP-1 drugs may help slow the cellular decline that underpins these conditions.
Corley stressed that the drugs are not reversing ageing but rather slowing some of the underlying biology. “Many of the biological processes we study in HIV are also central to ageing in the general population,” he said, adding that the findings deserve to be tested directly in larger trials.
What happens next?
The UC San Diego team plans to conduct larger, longer-term clinical trials to confirm the findings and determine how long the drugs can sustain their effects on biological ageing. This could inform optimal dosing and treatment strategies for people with HIV as well as the broader population. The researchers also intend to investigate whether combining semaglutide with other proven methods – such as a healthy diet, regular exercise and adequate sleep – could enhance the slowing of ageing.
However, important caveats remain. The studies evaluated biomarkers of ageing rather than direct clinical outcomes such as lifespan or rates of age-related disease. Larger trials are needed to confirm the effects in people without HIV, and long-term use of GLP-1 medications can be associated with side effects including gastrointestinal problems, gallbladder issues, pancreatitis and, rarely, more serious complications. In the UK, the cost of these drugs can be high, and NHS access is often restricted, leading many to seek private prescriptions.
“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 ageing biology and to identify which patients may benefit most,” said Corley.
