Wegovy and Ozempic seen to slow down biological ageing markers in HIV adults

A randomised clinical study has found that the active ingredient semaglutide slowed epigenetic markers linked to biological ageing in adults with human immunodeficiency virus-associated lipohypertrophy

Semaglutide – a widely used glucagon-like peptide-1 (GLP-1) receptor agonist and sold as Wegovy and Ozempic – has been shown to slow the accumulation of biological ageing markers in the DNA of adults with human immunodeficiency virus (HIV). Researchers said the study provided the first randomised, placebo-controlled clinical evidence in humans that the drug may affect epigenetic signals linked to ageing biology.

GLP-1 receptor agonists are used to treat obesity, type 2 diabetes and cardiovascular risk. Semaglutide, one of the best-known drugs in this class, has established effects on appetite regulation, blood glucose control and body weight. Researchers have also suggested that these medicines may influence biological ageing, although controlled human evidence has remained limited.

Researchers at the University of California San Diego, California, USA – and partner institutions – analysed data from a previously published clinical trial of 108 adults with HIV-associated lipohypertrophy, a condition in which excess fat accumulates around the abdomen. About half of the participants received weekly semaglutide injections, while the remaining participants received placebo injections.

The team used biological ‘epigenetic clocks’ to assess cellular ageing over the 32-week treatment period. These tools measure patterns of DNA methylation, chemical marks that help regulate gene activity without changing the underlying genetic sequence. Changes in these marks can indicate whether biological ageing processes appear to accelerate or slow.

People with HIV can show signs of accelerated ageing, even when antiretroviral therapy controls the underlying viral load of infection. Compared with the placebo group, participants who received semaglutide showed a broad pattern of slower biological ageing across epigenetic clocks linked to inflammation and to blood, brain, heart, kidney, liver and metabolic health.

The study also found that semaglutide slowed the pace of biological ageing by nine per cent – as measured by the DunedinPACE epigenetic clock – which estimates how quickly the body is biologically ageing. The drug also significantly slowed biological processes associated with the risk of all-cause mortality and age-related disease, as measured by the PCGrimAge epigenetic clock.

The researchers suggested that semaglutide may affect ageing biology through several related mechanisms. By reducing inflammation and metabolic stress, GLP-1 drugs may decrease chronic immune activation, a major driver of accelerated ageing in people with HIV. These medicines can also reduce visceral and ectopic fat which accumulates around the abdomen and organs and can contribute to inflammatory and metabolic signals associated with ageing.

“Emerging data also suggest that GLP-1 drugs may reprogramme certain cells in different organs which could help explain why we see effects across multiple aging clocks,” said Dr. Michael Corley, associate professor at the University of California San Diego School of Medicine and the Stein Institute for Research on Aging, and first author of the study.

Although the study focused on adults with HIV-associated lipohypertrophy, the researchers said the findings may have wider relevance because several biological processes observed in people with HIV are also central to ageing in the general population.

The findings followed a related pilot study in which Corley and colleagues examined semaglutide treatment in people with HIV and metabolic dysfunction-associated steatotic liver disease, also known as fatty liver disease. In that study, 24 weeks of semaglutide treatment reduced the rate of biological ageing in 42 per cent of participants, as measured by DunedinPACE. Those participants also had a greater reduction in liver fat than participants whose pace of ageing increased.

Taken together, the studies have added to evidence that GLP-1 drugs may influence biological pathways involved in ageing. However, the researchers cautioned that the results did not mean semaglutide reversed ageing.

“We are not saying that semaglutide reverses aging or makes people younger,” said Corley.

“What we are seeing is a signal that it may slow some of the biological processes associated with aging,” he added.

The researchers said larger clinical trials would be needed to confirm the findings, to determine how long the effects last and to establish the most appropriate dose and duration of treatment.

Corley serves as a scientific advisor for TruDiagnostic.

For further reading please visit: 10.1038/s41467-026-72861-3