Novo Nordisk and Eli Lilly Report GLP-1 Signals of Slowed Biological Aging at ARDD
Key Insights
Novo Nordisk and Eli Lilly presented early data at the ARDD conference suggesting semaglutide and tirzepatide may slow molecular measures of biological aging.
Novo reported proteomic clock differences of roughly two to three years, with up to four years on a clock tracking heart proteins, in a 10,052-person study.
Lilly's epigenetic sub-study within SURMOUNT-5 found all 15 age-unit clocks showed less aging than the 1.38 years of elapsed chronological time.
Novo Nordisk and Eli Lilly each presented early data at the Aging Research & Drug Discovery (ARDD) conference at Harvard suggesting that their GLP-1 receptor (search) agonists may slow molecular measures of biological aging, the first clinical readouts tying the drug class to aging clocks.
Novo's Global Project Leader for Research and Development, Nikolaj Roed, presented evidence that semaglutide and other GLP-1 receptor (search) agonists "may" support healthier aging, citing survival and physical function data and class-level evidence pointing to broader longevity potential. Roed 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 is no longer whether semaglutide reaches diseases relevant to health span and aging. "If the question is, 'Can semaglutide reach several diseases relevant to health span and aging?' we know we can say the answer is yes," he said. The next question, he added, is whether those effects are accompanied by changes to molecular measures of biological aging: "When you intervene with semaglutide, does it actually move the clocks in any direction? And the answer is yes."
Proteomic Clocks in 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 the drugs caused a broad slowdown in aging clocks, as much as four years on a clock that looks at heart proteins. "I think it's pretty clear that the organ age is shifting," Aguayo-Orozco said.
Semaglutide showed lower proteomic biological age estimates across cardiovascular outcome trials, with a rapid effect within 13 to 20 weeks that was either sustained or enhanced over 150 weeks. Proteomic signatures suggested improvements in vitality and locomotion. Modeled from SELECT trial effect estimates in a UK real-world semaglutide cohort of 19,117 people, remaining life-year gains of 1.9 years overall were projected across every age group, with the largest gain at younger treatment ages.
Lilly's Epigenetic Sub-Study Within SURMOUNT-5
Kevin Duffin, vice president for aging research at Eli Lilly, presented early epigenetic data suggesting tirzepatide "may" slow biological aging, framing it as a small pilot to test methods and check consistency rather than a definitive result. "All the clocks are telling a consistent story that we're seeing a reduction in age," Duffin said. "It's not like we're going to reverse age by 30 years or something, but it's a significant reduction."
The data came from an epigenetic sub-study within SURMOUNT-5, Lilly's head-to-head trial of tirzepatide against semaglutide. The sub-study took paired whole-blood samples from tirzepatide-treated participants at baseline and at week 72, equivalent to 1.38 elapsed years, with 91.5% of participants on the 15 mg dose by week 72. Zymo Research (search) and TruDiagnostic (search) independently generated 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 baseline and week 72 data.
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 over the study period. On pace-of-aging measures, the Zymo data showed DunedinPACE falling from a median of 1.13 to 1.08. TruDiagnostic (search)'s data reproduced the direction of travel across six second-generation clocks, including GrimAge V1 and V2, and showed larger effects on the DunedinPACE and FraminghamPACE pace clocks.
Organ clocks suggested lower predicted age in the immune system, kidney, liver and cardiovascular organs, which Lilly said fits the improved clinical outcomes seen in patient trials. Methylation-based protein predictions, known as EpiScores, found 21 proteins significantly changed at week 72. The pattern pointed to reduced innate inflammatory signalling, metabolic inflammation and tissue damage, and increased adaptive immune surveillance, and it replicated 28 previously reported diabetes-associated protein signatures. Lilly drew parallels with findings from caloric restriction and bariatric surgery studies.
Caveats and Open Questions
Lilly described the presentation as heavily caveated. The sub-study was small and single-arm, with no placebo or control. Follow-up was short relative to the measurement error of the clocks, and some clock signals were discordant or unresolved. Several predicted protein changes did not match actual measurements, including VCAM1, SHBG and TNFRSF1B. The clocks themselves were not trained on randomized controlled trial or longitudinal data. Lilly called the findings preliminary and hypothesis-generating, needing replication in larger, ideally randomized studies, and said it plans to expand the work to semaglutide and other chronic weight management studies.
Steve Horvath, a professor at the University of California, Los Angeles, credited with inventing aging clocks, said the emerging data could provide "evidence that these GLP-1 drugs are actually what is known as geroprotectors, medications that slow or possibly even reverse biologic aging." He described a two-year effect as "pretty strong." But Horvath cautioned that he is not ready to take the drugs himself. "Clearly, the drugs have many benefits in obese people, but I did not yet see sufficient evidence that they will benefit skinny people," he said. "I guess we will have to wait."
Vadim Gladyshev, a Harvard biologist who assisted Novo with its molecular measurements, said: "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 cautioned that GLP-1 drugs have side effects, including muscle loss.
Yuge Ji, a biologist who previously worked in the field and now runs a startup, Reflector Bio, said the studies are a boost for aging clock science. "The clock people have been pushing for a decade to get this kind of study done," she said.
A Regulatory Path for Longevity Drugs
Answers on healthy populations could begin to emerge in a year or two. In January, the US agency ARPA-H (search) put $38 million toward a study in Texas that will attempt to determine whether semaglutide has anti-aging effects in healthy people over 60, looking at changes in cognition, mobility, and acuity of the senses. That project also seeks to help define a regulatory pathway for anti-aging drugs and to "build a new therapeutic industry" around longevity.
With both Novo and Lilly now applying biological-age readouts to their GLP-1 franchises, the industry's two largest obesity (search) players are building the evidence base that an FDA panel said the field itself must supply. Novo said it is exploring consumer prescription indications across immune-mediated inflammatory diseases, pain and addiction, and women's and men's health, with assets including incretins, amylins, anti-inflammatory assets and other mechanisms of action.