Could a diabetes drug change the future of neurodegenerative disorders?

GLP-1 is a natural hormone that stimulates insulin release and promotes satiety, but is rapidly broken down by enzymes. (2) GLP-1RAs with longer half-lives have transformed the treatment of metabolic diseases, with Novo Nordisk’s semaglutide (marketed as Ozempic and Wegovy) dominating the T2DM and obesity market, accounting for 59% of the company’s total sales over the past year. (3) Eli Lilly’s tirzepatide (Mounjaro and Zepbound) is also gaining traction. (4) Now, these drugs may also hold the potential to revolutionise the treatment of neurodegenerative disorders.

Epidemiological studies indicate that T2DM significantly increases the risk of developing both AD and PD. (5) Insulin resistance serves as a critical bridge between these conditions, highlighting the relevance of the gut-brain axis—complex communication between digestive system and brain—as a key player in neurodegeneration. (6) Given this link, it follows that GLP-1RAs could treat these diseases.

Research shows that GLP-1Rs are present in the brain, and several GLP-1RAs can cross the blood-brain barrier (BBB), allowing them to influence brain function. (7) Preclinical studies using animal models of AD and PD suggest that GLP-1 agonists provide neuroprotection, reduce neuroinflammation, and slow cognitive decline in AD and improve motor function in PD. (8, 9, 10)

Despite these initially promising preclinical results, further trials are needed to confirm the efficacy, safety, and disease-modifying potential of GLP-1RAs in neurodegenerative conditions. Some trials have shown encouraging results—such as the phase II trial of lixisenatide, which suggested a potential slowing of motor symptom progression in PD. (11) However, not all studies have been as successful: a recent phase III study led by UCL researchers, recently published in The Lancet, found no evidence to support exenatide as a disease-modifying treatment for PD. (12)

Data from clinical trials for AD are more limited, but anticipation is high for Novo Nordisk’s phase III trials (EVOKE and EVOKE Plus), which aim to evaluate semaglutide’s potential disease-modifying effects in AD. (13) The results of these trials could mark a turning point for the use of GLP-1 drugs in neurodegenerative disorders. If proven effective, they could

transform how we treat these conditions, potentially delivering another revolutionary breakthrough for Novo Nordisk.

The journey of GLP-1s highlights the value of initiating path-to-market strategy in the early stages of drug development, and the importance of continuous lifecycle planning, even as post-approval data accumulates, to maximise its potential and extend the portfolio of opportunity.

References

1.Zheng, Z. et al. Glucagon-like peptide-1 receptor: mechanisms and advances in therapy. Signal Transduct. Target. Ther. 9, 1–29 (2024).

2.Collins, L. & Costello, R. A. Glucagon-Like Peptide-1 Receptor Agonists. in StatPearls (StatPearls Publishing, Treasure Island (FL), 2025).

3.Kansteiner, F. Novo Nordisk predicts milder growth in 2025 after obesity star Wegovy doubles sales in Q4 | Fierce Pharma. https://www.fiercepharma.com/pharma/novo-nordisk-predicts-milder-sales-growth-2025-after-obesity-star-wegovy-doubles-numbers-q4 (2025).

4.Lilly’s Zepbound (tirzepatide) superior to Wegovy (semaglutide) in head-to-head trial showing an average weight loss of 20.2% vs. 13.7% | Eli Lilly and Company. https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head.

5.Santiago, J. A., Karthikeyan, M., Lackey, M., Villavicencio, D. & Potashkin, J. A. Diabetes: a tipping point in neurodegenerative diseases. Trends Mol. Med. 29, 1029–1044 (2023).

6.S, H., T, T. & Vellapandian, C. Gut-Brain Axis: Unveiling the Interplay Between Diabetes Mellitus and Alzheimer’s Disease. Cureus 16, e68083.

7.Muscogiuri, G., DeFronzo, R. A., Gastaldelli, A. & Holst, J. J. Glucagon-like Peptide-1 and the Central/Peripheral Nervous System: Crosstalk in Diabetes. Trends Endocrinol. Metab. 28, 88–103 (2017).

8.Kopp, K. O., Glotfelty, E. J., Li, Y. & Greig, N. H. Glucagon-like peptide-1 (GLP-1) recepto agonists and neuroinflammation: implications for neurodegenerative disease treatment. Pharmacol. Res. 186, 106550 (2022).

9.Hansen, H. H. et al. The GLP-1 Receptor Agonist Liraglutide Improves Memory Function and Increases Hippocampal CA1 Neuronal Numbers in a Senescence-Accelerated Mouse Model of Alzheimer’s Disease. J. Alzheimers Dis. 46, 877–888 (2015).

10.Kalinderi, K., Papaliagkas, V. & Fidani, L. GLP-1 Receptor Agonists: A New Treatment in Parkinson’s Disease. Int. J. Mol. Sci. 25, 3812 (2024).

11.Meissner, W. G. et al. Trial of Lixisenatide in Early Parkinson’s Disease. N. Engl. J. Med. 390, 1176–1185 (2024).

12.Vijiaratnam, N. et al. Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson’s disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial. The Lancet 405, 627–636 (2025).

13.Cummings, J. L. et al. evoke and evoke+: design of two large-scale, double-blind, placebo-controlled, phase 3 studies evaluating efficacy, safety, and tolerability of semaglutide in early-stage symptomatic Alzheimer’s disease. Alzheimers Res. Ther. 17, 14 (2025).