Novo Nordisk and Eli Lilly report first clinical signs GLP-1 drugs slow biological aging

Novo Nordisk and Eli Lilly have presented early clinical data suggesting their GLP-1 receptor agonists, semaglutide and tirzepatide, may slow molecular measures of biological aging. Speaking at the Aging Research & Drug Discovery (ARDD) conference at Harvard, researchers from both companies described aging-clock readouts that shifted in patients taking the drugs, the first clinical data connecting the blockbuster obesity and diabetes class to such measures.

Novo's proteomic clocks across 10,052 participants

Novo's study drew blood from 10,052 people, half on the drug and half on placebo, at baseline and again months later. The samples were measured with proteomic clocks, which use levels of key proteins to predict a person's age and risk of dying. The company found a broad slowdown in aging clocks, as much as four years on a clock based on heart proteins.

Nikolaj Roed, Novo's global project leader for research and development, said the company has been seeing "improved biological age in our patients across trials and across different tissues," with an overall difference of around two to three years. Alejandro Aguayo-Orozco, a senior scientific director at Novo, told the meeting that the question of whether semaglutide can reach diseases relevant to health span and aging has already been answered yes, and that the next question was whether the clocks move under the drug. They do, he said.

Semaglutide showed lower proteomic age estimates across cardiovascular outcome trials, with a rapid effect within 13 to 20 weeks that was either sustained or enhanced over 150 weeks. When Novo modeled SELECT trial effect estimates onto a UK real-world semaglutide cohort of 19,117 people, it projected remaining life-year gains of 1.9 years overall, with the largest gain at younger treatment ages.

Lilly's epigenetic pilot inside SURMOUNT-5

Kevin Duffin, vice president for aging research at Eli Lilly, presented an epigenetic sub-study within SURMOUNT-5, Lilly's head-to-head trial of tirzepatide against semaglutide. The pilot took paired whole-blood samples from tirzepatide-treated participants at baseline and at week 72, equivalent to 1.38 elapsed years, with Zymo Research and TruDiagnostic independently generating the methylation data so the two sets could be checked against each other. After quality control, the analysis covered 82 unique subjects, 71 of whom had paired samples.

All 15 age-unit epigenetic clocks showed less aging than the 1.38 years of chronological time that had passed. Two clocks reached statistical significance, with median gains of 1.1 and 0.7 years. On pace-of-aging measures, the Zymo data showed DunedinPACE falling from a median of 1.13 to 1.08, and TruDiagnostic's data reproduced the direction of travel across six second-generation clocks, including GrimAge V1 and V2. Organ clocks suggested lower predicted age in the immune system, kidney, liver and cardiovascular system, while methylation-based protein predictions pointed to reduced innate inflammatory signalling and increased adaptive immune surveillance.

"All the clocks are telling a consistent story that we're seeing a reduction in age," Duffin said, while framing the work as a small pilot to test methods rather than a definitive result.

Heavy caveats

Lilly described the presentation as heavily caveated. The sub-study was small and single-arm with no placebo or control group, follow-up was short relative to the measurement error of the clocks, and some clock signals were discordant. Several predicted protein changes, including VCAM1, SHBG and TNFRSF1B, did not match actual measurements, and the clocks themselves were not trained on randomized or longitudinal data. Lilly called the findings preliminary and hypothesis-generating, needing replication in larger and ideally randomized studies, and said it plans to expand the work to semaglutide and other chronic weight management studies.

Outside researchers were similarly measured. Steve Horvath, the University of California, Los Angeles professor credited with inventing aging clocks, said the emerging data could provide evidence that GLP-1 drugs are "geroprotectors" and described a two-year effect as "pretty strong," but said he is not ready to take the drugs himself, citing insufficient evidence of benefit for people who are not obese. Vadim Gladyshev, a Harvard biologist who assisted Novo with its molecular measurements, said that in an unhealthy population "I do think it's an anti-aging drug. But in a healthy population, no one knows." Several people at the meeting also cautioned that GLP-1 drugs carry side effects, including muscle loss.

Why it matters

These are the first clinical readouts tying GLP-1 drugs to aging clocks, reframing the industry's biggest drug class as a candidate for longevity medicine. The practical consequence is drug development: answers on healthy populations could begin to emerge within a year or two, aided by a $38 million ARPA-H-funded study in Texas that will test whether semaglutide has anti-aging effects in healthy people over 60, looking at cognition, mobility and sensory acuity, while also seeking to define a regulatory pathway for anti-aging drugs. With both Novo and Lilly applying biological-age readouts to their GLP-1 franchises, the two largest obesity drug makers are building the evidence base that an FDA panel said the longevity field itself must supply, and Novo is already exploring further prescription indications spanning immune-mediated inflammatory disease, pain, addiction and men's and women's health.