From weight-loss drug to 'fountain of youth': Big Pharma bets on GLP-1 as anti-aging treatment

Expectations are growing that glucagon-like peptide-1 (GLP-1) receptor agonists — the drug class that has reshaped the global pharmaceutical market as treatments for diabetes and obesity — could evolve into anti-aging therapies capable of extending healthy lifespan.

Global pharmaceutical giants are pushing the drugs' applications well beyond weight loss, targeting a broad range of age-related conditions including cardiovascular disease, chronic kidney disease, non-alcoholic steatohepatitis (MASH) and Alzheimer's disease. Analysts say South Korea's biotech ecosystem should also be paying close attention to next-generation anti-aging targets that could follow GLP-1.

According to a report titled "Evolution of GLP-1 Class Drugs: Anti-aging Strategy," recently published by the Korea Biotechnology Industry Organization's Bio-Economy Research Center, representatives of Novo Nordisk and Eli Lilly drew attention at the Aging Research and Drug Discovery conference when they raised the possibility that GLP-1 drugs could become "the first drugs associated with aging." GLP-1 is a hormone that acts on receptors distributed throughout the body — including the pancreas and brain — to stimulate insulin secretion and suppress appetite.

Following the first-generation Saxenda (liraglutide) in 2014, the second-generation Wegovy (semaglutide) demonstrated an average weight loss of 14.9 percent over 68 weeks in the Phase 3 STEP 1 trial. Eli Lilly's Mounjaro and Zepbound (tirzepatide) showed an average reduction of 20.9 percent over 72 weeks in the Phase 3 SURMOUNT-1 trial. Oral semaglutide also recorded a significant 15.1 percent weight loss over 68 weeks in the OASIS 1 clinical trial.

Recent clinical data are building a case that GLP-1 drugs can ease systemic age-related complications beyond metabolic improvement. A pooled analysis of large-scale cardiovascular trial data found that the risk of major adverse cardiovascular events (MACE) — including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke — fell by about 14 percent, while the risks of all-cause mortality and heart failure hospitalization declined by 12 percent and 11 percent, respectively.

Particularly notable was the SELECT trial of semaglutide, which enrolled 17,604 non-diabetic obese patients and observed cardiovascular improvements before maximum weight loss was achieved. The finding raised the possibility that an independent mechanism directly protecting the cardiovascular system — separate from weight reduction — may be at work.

Cell and animal studies are confirming multiple cellular-protection mechanisms associated with GLP-1. Antioxidant activity — reducing reactive oxygen species (ROS) and activating the NRF2 pathway — has been observed independently of blood glucose changes, suggesting a direct cell-protective effect.

GLP-1 has also been shown to promote autophagy, the process by which damaged proteins and organelles are broken down and cleared, potentially alleviating hepatocyte damage and lipotoxicity. In the context of neurological disease, studies have reported that GLP-1 may reduce synaptic damage and inhibit the accumulation of amyloid beta and tau in Alzheimer's disease, as well as alpha-synuclein in Parkinson's disease, potentially slowing cognitive and motor decline. Drug repurposing research is now underway through clinical trials including EVOKE and Exenatide-PD3.

The global market is actively debating aging biology-based treatment strategies for the era after GLP-1. The report highlighted the NLRP3 inhibitor — a mediator of chronic inflammation known as "inflammaging" — as a leading candidate. Animal model studies have reported that NLRP3 deficiency extended the average lifespan of male mice by about 34 percent and maximum lifespan by 29 percent, spurring development efforts by companies including BioAge Labs and Insilico Medicine.

Other major research targets identified in the report include cGAS-STING inhibitors, which block the pathway by which cytosolic DNA leakage triggers chronic inflammation; apelin, an exercise-signaling molecule involved in muscle regeneration and cardiac function; IL-11 inhibitors, which block cytokines that drive chronic inflammation and fibrosis; and modulators of the integrated stress response (ISR), which maintains protein homeostasis.

However, the US Food and Drug Administration does not recognize aging as an independent disease indication, meaning anti-aging clinical trials are currently designed around individual age-related conditions. South Korean biotech firms, including GI Innovation — whose executive vice president Kim Guk-hwan co-authored the report — are also directing attention toward next-generation anti-aging mechanism research and unmet medical needs, drawing on their metabolic disease platform capabilities.

The report urged domestic companies to "explore the effects of GLP-1 class drugs on aging-related diseases such as sarcopenia, cardiovascular disease, kidney disease and neurodegenerative disease, given that they are already building capabilities around obesity and metabolic disease treatments." It added that firms should "proactively secure the expertise needed to identify new indications and aging-related clinical benefits by combining therapeutic target discovery technology using AI, multi-omics and bioinformatics, and to rapidly translate those findings into research, development and commercialization."