How GLP-1 became the breakthrough multi-organ drug of the decade.

GLP-1 drugs have quickly moved beyond their image as “just weight-loss medicines.”

Recent U.S. approvals, Zepbound (tirzepatide) for sleep apnea in 2024, Wegovy (semaglutide) for MASH with fibrosis in 2025, and Ozempic (semaglutide) for reducing the risk of kidney disease worsening, show how these medicines are now being used for a wide range of health issues. 

This shift is backed by growing clinical evidence. A UC San Diego study found that people with colon cancer who took semaglutide or tirzepatide had less than half the five-year death rate of those who did not. Real-world data from Munich and Harvard also showed up to an 18% drop in heart attacks and strokes. 

GLP-1 receptors are found across the body in the heart, liver, kidneys, fat tissue, and even the brain. As a result, GLP-1 medicines can reduce inflammation, improve how organs use energy, protect blood vessels, and support brain health. The next wave of drugs is expanding this even further. Dual and triple agonists add new pathways, such as GIP, glucagon, or amylin, to strengthen or target effects in specific organs.

Key Applications of GLP-1 Drugs Across Different Organs

GLP-1 drugs are now being tested far beyond diabetes and obesity. They have already entered Phase 3 trials to protect the heart and kidneys, as well as to treat obesity-related heart failure (HFpEF). Results from Alzheimer’s trials are expected in 2025. Phase 3 studies are also underway for MASH and sleep apnea, while earlier trials show promise in areas like addiction and PCOS.

1. Eli Lilly’s oral GLP-1 for sleep apnea & hypertension

Lilly is arguably the most aggressive mover in broadening the use of GLP-1 beyond diabetes and weight loss. They’re mixing GLP-1, GIP, and glucagon to tackle a wide range of complex, multi-organ conditions, including cardiometabolic issues, liver diseases, and even neurological disorders.

Their Tirzepatide (which you probably know as Zepbound) is already approved for obesity, type 2 diabetes, and sleep apnea. This is their foundation for cardiometabolic health and liver diseases. Then there’s Retatrutide, a triple agonist currently in Phase 2, which is expanding its reach even further by helping with fat metabolism, lipid profiles, and blood pressure. 

Orforglipron, Lilly’s oral GLP-1 pill in Phase 3 trials, which adds an extra layer of convenience and has the potential to help with diseases like sleep apnea and even neurodegenerative conditions.

Building on the proven success of Tirzepatide and Orforglipron, Lilly’s next strategic move will likely focus on expanding GLP-1 therapies into cardiovascular and neurodegenerative diseases. These areas align with the broader, multi-organ benefits these treatments offer.

2. Novo Nordisk’s CagriSema lowers BP & CRP levels

While Lilly is moving toward triple-agonist drugs, Novo Nordisk is building on semaglutide by combining it with amylin therapy. 

Their combo drug, CagriSema, which pairs semaglutide with cagrilintide, has shown clear improvements in blood pressure, cholesterol, and overall vascular health. It also supports the liver by improving fat clearance and reducing inflammation, making it a strong candidate for NASH treatment. 

Early data even shows a 70% drop in a primary inflammatory marker linked to heart disease, and about 40% of patients were able to reduce or stop their blood pressure medicines. Fewer patients on CagriSema were at medium-to-high risk of developing cardiovascular disease over the next decade.

Semaglutide on its own is also showing benefits beyond metabolism. Studies indicate it can help protect the kidneys, brain, and retina because of its anti-inflammatory and anti-fibrotic effects. In one retinal study, semaglutide boosted tissue survival by nearly 56%, improved mitochondrial function, and showed no toxicity, supporting its potential in conditions like stroke, Alzheimer’s, and Parkinson’s disease.

3. Dual-action drug from Merck targets NAFLD and NASH

Merck is taking a liver-focused approach to treating metabolic diseases such as NAFLD and NASH through dual GLP-1/glucagon co-agonists, with its lead investigational drug, efinopegdutide (MK-6024). Efinopegdutide is a new kind of injectable medicine being studied for people with non-alcoholic fatty liver disease (NAFLD) — a condition where too much fat builds up in the liver, often linked to obesity or type 2 diabetes. Right now, there are no approved treatments for the more serious form of this condition, called non-alcoholic steatohepatitis (NASH), so researchers are exploring new options.

In a recent phase IIa clinical trial, researchers compared efinopegdutide (10 mg once weekly) with semaglutide (1 mg once weekly) in people with NAFLD. After 24 weeks, those taking efinopegdutide had a 72.7% reduction in liver fat, compared with 42.3% with semaglutide. This is a significant improvement. Both medicines also led to weight loss (8.5% for efinopegdutide and 7.1% for semaglutide). But the greater liver fat reduction seen with efinopegdutide suggests it does more than just help people lose weight; it may directly improve liver function.

Although it’s still in preclinical development, Merck’s approach stands out from competitors like Lilly and Novo, especially in treating liver and metabolic diseases. Their focus on liver-targeted therapies could make it easier to get regulatory approval. 

GLP-1 2.0 in the Brain and Beyond

Beyond big pharma, a cluster of biotechs and academic groups is exploring where GLP-1 biology might go next. 

D&D Pharmatech’s NLY01 (pegsebrenatide) is a long-acting GLP-1 receptor drug designed to protect the brain in diseases like Parkinson’s, Alzheimer’s, and Multiple Sclerosis (MS). It can cross the blood–brain barrier and works by reducing brain inflammation, calming overactive immune cells, and preventing damage to nerve cells. In animal studies, NLY01 has shown promise in protecting neurons and reducing inflammation, but recent research in MS models found no clear benefit in repairing nerve damage. While early human trials in Parkinson’s disease didn’t meet the main goals, NLY01 still shows potential as a brain-protective treatment and continues to be studied further.

Dana-Farber Cancer Institute is developing structurally stabilized GLP-1 peptides using hydrocarbon-stitching technology. Their lead peptide, SAH-GLP-1, shows excellent stability and targets Alzheimer’s, Huntington’s, and cardiovascular diseases.

Conclusion

GLP-1 sales have skyrocketed from $300 million in 2018 to a projected $30 billion by 2024, with half of that growth coming from non-diabetes and non-obesity uses. The real challenge now is identifying new opportunities beyond existing applications.

While GLP-1s show promise in neuroprotection, including for Alzheimer’s, there are still significant gaps in CNS penetration and treatments for neurodegenerative diseases. This represents a vast, untapped market where both biotech and pharma can make a substantial impact. Companies should focus on overcoming the blood-brain barrier and developing treatments for neuroinflammation and cognitive decline, as early investment in these areas could provide a significant advantage. 

As a next step, explore the GLP-1 food landscape supporting weight loss and metabolic health treatments, and how companies are entering this space.