^{Figure 1: Percentage risk reduction with GLP-1 therapy across indications based on selected real-world studies: Sources: 1. Lin H, Tsai Y, Liao P, Wei JC. Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. JAMA Netw Open. 2025;8(7):e2521016. doi:10.1001/jamanetworkopen.2025.21016 2. Xie, Y., Choi, T. & Al-Aly, Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med 31, 951–962 (2025). https://doi.org/10.1038/s41591-024-03412-w, 3. GLP-1 Receptor Agonists May Modestly Reduce Risk of Fourteen Obesity-Related Cancers for People with Diabetes - ASCO. (2025). Asco.org. https://www.asco.org/about-asco/press-center/news-releases/glp-1-receptor-agonists-may-modestly-reduce-risk-obesity-related-cancers-people-with-diabetes}

Individual real-world studies (RWS) can, however, be non-representative. The above-mentioned Veterans Affairs study, for example, was skewed towards older white males; thus, challenging its generalisability. Combining real-world datasets in diverse populations is essential to achieve broader applicability. On the other hand, RWE lacks the ability to establish causality by minimising confounding effects which is a key strength of randomised clinical trials (RCTs). This underscores the need for both RWE and RCTs in parallel and reinforces the need to need to run clinical trials that reflect real-world populations, a topic explored in more detail in our blog “Obesity trials on trial”

Some health improvement seen with GLP-1 therapy may be a direct effect of weight loss, rather than unique drug effect as seen by improvements in liver and kidney health⁴. This is highlighted by the new European Association for the Study of Obesity (EASO) guidelines on obesity management via pharmacotherapy dividing obesity-related complications into either fat mass, or metabolic dysfunction associated comorbidities. In both these instances, conditions tend to improve due to body weight dropping making it important to recognise which benefits are due to weight loss rather than any specific pharmacological action.

The exciting “beyond obesity” frontier for GLP-1 drugs is their potential to treat conditions where inflammation, or other non-obesity factors, are the primary cause. In these cases, GLP-1s appear to exert direct pharmacological effects on specific tissues, independent of weight change. For example, GLP-1 receptors are present in key brain regions involved in cognition and reward⁵. Studies indicate that GLP-1 therapies can reduce inflammation, protect against neurodegeneration, regulate hormone production and even modulate the brain’s reward system ^6,7 . These findings demonstrate the potential of GLP-1s in directly addressing neurological conditions where inflammation and dysregulated signalling are central issues. Large-scale RCTs are required to rigorously validate these early findings, and encouragingly, we are already starting to see several studies exploring these areas.

R&D pipeline: where are we now and what’s next

Currently, GLP-1s have received regulatory approval from both the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of: T2D; chronic weight management in individuals with obesity or overweight; reducing cardiovascular risk in adults with established cardiovascular disease (CVD); management of chronic kidney disease (CKD); obstructive sleep apnoea (OSA); and more recently, metabolic-dysfunction associated steatohepatitis (MASH).

Semaglutide is approved as Ozempic for T2D and CKD in people with T2D, as Wegovy for obesity and reducing the risk of serious heart problems in adults with CVD and either obesity or overweight, and as Rybelsus as an oral medication for T2D. In August 2025, the FDA also approved Wegovy for the treatment of noncirrhotic MASH with moderate to advanced liver fibrosis⁸. Tirzepatide is approved as Mounjaro for T2D and as Zepbound for chronic weight management and, notably by the FDA, for treatment of moderate to severe OSA in adults with obesity. Liraglutide is approved as Victoza for T2D and reducing the risk of serious heart problems in individuals with T2D, and Saxenda for weight management.

^{Figure 2: FDA and EMA approved GLP-1 molecules and selected clinical trials outside obesity; Sources: GLP-1 Pipeline Update: May 2025 - Prime Therapeutics - Portal, clinicaltrials.gov, Analytics Link.}

^{HFpEF: Heart Failure with Preserved Ejection Fraction; MASH: Metabolic Dysfunction-Associated Steatohepatitis; CVD: Cardiovascular Disease; CKD: Chronic Kidney Disease; T2DM: Type 2 Diabetes Mellitus}

Industry-sponsored trials are actively underway (or have already been completed) exploring the potential for GLP-1 based therapies in a range of new indications. These include Alzheimer’s disease, Parkinson’s disease and alcohol use disorder (Figure 2). These studies aim to extend the therapeutic indications of currently approved GLP-1 molecules beyond their established roles in diabetes, obesity and CVD management.

As part of the evolving R&D pipeline, Figure 3 summarises the emerging research frontiers into the potential therapeutic applications of GLP-1s beyond cardiometabolic conditions, including neurodegeneration, addiction, mental health, cancer, women’s health and asthma.

Neurodegenerative diseases

One of the most closely watched areas is GLP-1’s potential in treating neurodegenerative diseases. Novo Nordisk has launched two large Phase III trials (EVOKE and EVOKE+) to assess whether semaglutide can slow cognitive decline in participants with early-stage Alzheimer’s disease. The highly anticipated results are expected to readout in September 2025⁹.

Early optimism in the use of GLP-1 therapies for Parkinson’s disease has been tempered by the recent failure of a Phase III exenatide trial which did not show any benefits of slowing Parkinson’s progression¹⁰. This was disappointing after smaller studies suggested benefits where GLP-1 improved motor symptoms. It emphasises the difficulty of translating success in preclinical trials across the pipeline to clinical outcomes. However, research in this area continues with several companies exploring novel GLP-1 treatment strategies. Peptron has developed PT320, a novel sustained-release exenatide formulation designed to penetrate the blood-brain barrier more effectively. Phase II trials are underway in South Korea following successful early-stage studies. Kariya Pharmaceuticals has taken a unique approach with KP405, a first-in-class dual GLP-1/GIP receptor agonist with the potential to synergistically reduce neuroinflammation, enhance mitochondrial function and support neuronal survival. A Phase I trial is currently in progress exploring the safety of KP405 as a new Parkinson’s treatment.

Addiction

GLP-1s are being explored for their potential role in reducing the risk of substance use disorders. This is likely due to their role in dampening the brain’s reward circuits. GLP-1 medications activate receptors in key dopamine-rich areas such as the ventral tegmental areas (VTA) and the nucleus accumbens (Nac). This reduces drug-induced dopamine release and makes addictive substances feel less rewardin¹¹. Preclinical studies have shown that GLP-1s can reduce self-administration of various addictive substances including alcohol, nicotine and cocaine in rodent models¹², laying the groundwork for further investigation in human trials. Several pharmaceutical companies are actively pursuing GLP-1 based therapies for alcohol use disorder (AUD), signalling a growing interest in expanding their use beyond metabolic conditions. Eli Lilly is leading with a phase II trial initiated in early 2025 to evaluate mazdutide, a GLP-1/GIP dual agonist, in participants with AUD. Novo Nordisk is also conducting a Phase II trial investigating semaglutide and cagrilintide, with alcohol consumption as a secondary endpoint alongside liver damage. Meanwhile, Altimmune has repurposed its dual GLP-1/glucagon agonist, pemvidutide, in a Phase II trial focused on reducing heavy drinking days as a primary endpoint.

While alcohol is currently the primary focus, interest is expanding to other substance use disorders, including nicotine dependence and opioid use. Considering the significant public health burden and limited availability of effective treatments, these trials represent a high-stakes opportunity to redefine how substance use disorders are managed.

Asthma

RWE showed that individuals with obesity and asthma treated with GLP-1s experienced better symptom control and fewer exacerbations compared to non-users. These improvements occurred even with modest weight loss suggesting the possibility that GLP-1s have direct anti-inflammatory effects in the airways.

Women’s Health

In women’s health, GLP-1s are being investigated for polycystic ovary syndrome (PCOS) and related fertility issues. A 2023 meta-analysis found that GLP-1 treatment significantly increased the natural pregnancy rate and improved menstrual regularity in women with PCOS¹². These benefits can be partly attributed to weight loss and reduced insulin resistance through GLP-1 use as this helps reduce insulin-driven androgen excess and restore regular ovulation¹³. GLP-1s, however, may also exert direct hormonal effects as GLP-1 receptors can be found across the hypothalamus-pituitary-ovarian (HPO) axis and influence gonadotropin release and follicle development. The phenomenon of “Ozempic babies”, where individuals can conceive more easily on GLP-1 therapy, underscores how closely metabolic and reproductive health interact.

Final thoughts

The potential for rapid expansion of GLP-1 therapies into new indications raises important questions about the future of medical treatment, research priorities and healthcare policy. The expectations are high and for GLP-1s to fulfil their enormous potential, innovators should focus on following priorities:

1. Run rigorous RCTs and expand RWS: Much of the enthusiasm has been driven by real‑world evidence and observational studies. Large, well‑controlled randomised trials are needed to characterise benefits and risks, with designs that distinguish weight‑loss‑mediated effects from direct pharmacology. Pre‑specify mechanistic endpoints, include appropriate comparators, and ensure diverse, representative populations. In parallel, health systems should consider commissioning large RWS to understand the full benefits of GLP-1s in routine use including outcomes in the many patients currently using these drugs out-of-pocket.
2. Monitor safety and risks proactively: The Veterans Affair study¹ found GLP-1 use was associated with an increased risk of 19 conditions, mainly affecting the digestive and musculoskeletal system. Vulnerable populations such as frail patients, pregnant women, adolescents and the elderly may be more susceptible to adverse effects like muscle loss or nutritional deficits. Additional treatments such as muscle preserving agents or intermittent dosing strategies may need to be investigated.
3. Plan for reimbursement and budget impact: GLP-1 medications are generally not reimbursed solely for weight loss in most countries, although this is beginning to change. Notably, the NHS in the UK now covers both Wegovy and Mounjaro for obesity treatment. Likewise, Switzerland’s basic health insurance reimburses Wegovy for obesity¹⁴ and major health funds in Israel have introduced subsidies for Wegovy and Mounjaro to support weight loss treatment¹⁵. However, such coverage comes with strict eligibility requirements, such as patients needing an extremely high BMI and associated health conditions. Typically, payers have justified covering GLP-1 therapies by targeting co-morbidities rather than obesity alone. For example, Medicare will cover Eli Lilly’s Zepbound for OSA¹⁶ and Novo Nordisk’s Wegovy for lowering the risk of CVD¹⁷. These cases illustrate how reimbursement often follows the pathway of treating serious obesity-related health complications first. As GLP-1s expand their indications, pressure is building on payors to reassess reimbursement policies.
4. Advance equitable access and shape policy: GLP-1 medications have the potential to significantly benefit populations with lower socioeconomic status, yet these groups often face the greatest barriers to access. Crucially, just as GLP-1s are improving their benefits beyond weight loss, they are also becoming more accessible and inexpensive than ever. Liraglutide and exenatide are already off-patent and semaglutide will begin losing exclusivity in several large countries from 2026 (read more in our blog “Off-patent semaglutide in 2026”). Statins provide a powerful parallel for GLP-1 therapies, demonstrating how a medication can transition from specialist use to widespread preventative care once cost barriers are removed. When statins became inexpensive generics, clinical guidelines broadened eligibility, public health programmes expanded access, and reimbursement policies adapted to support equitable uptake. GLP-1s are now approaching a similar turning point. Policymakers should drive more equitable access of GLP-1 treatments as the benefits become more significant and proactively update guidelines for preventative use to ensure broader eligibility and earlier intervention.

GLP-1s are increasingly proving themselves to be more than weight-loss agents, with the potential to touch nearly every aspect of human health. If their promise holds, these ‘everything drugs’ may mark the turning point where sick care finally becomes health care.

References:

¹Xie, Y., Choi, T., & Al-Aly, Z. (2025). Mapping the effectiveness and risks of GLP-1 receptor agonists. Nature medicine, 31(3), 951–962. https://doi.org/10.1038/s41591-024-03412-w
²Lin H, Tsai Y, Liao P, Wei JC. Neurodegeneration and Stroke After Semaglutide and Tirzepatide in Patients With Diabetes and Obesity. JAMA Netw Open. 2025;8(7):e2521016. doi:10.1001/jamanetworkopen.2025.21016
³GLP-1 Receptor Agonists May Modestly Reduce Risk of Fourteen Obesity-Related Cancers for People with Diabetes - ASCO. (2025). Asco.org. https://www.asco.org/about-asco/press-center/news-releases/glp-1-receptor-agonists-may-modestly-reduce-risk-obesity-related-cancers-people-with-diabetes
⁴GLP-1 medicines and kidney disease: what you need to know. (2025, July). Kidney Care UK. https://kidneycareuk.org/kidney-disease-information/treatments/glp-1-medicines-and-kidney-disease/
⁵Fu, Z., Gong, L., Liu, J., Wu, J., Barrett, E. J., Aylor, K. W., & Liu, Z. (2020). Brain Endothelial Cells Regulate Glucagon-Like Peptide 1 Entry Into the Brain via a Receptor-Mediated Process. Frontiers in Physiology, 11. https://doi.org/10.3389/fphys.2020.00555
⁶Mehan, S., Bhalla, S., Siddiqui, E. M., Sharma, N., Shandilya, A., & Khan, A. (2022). Potential Roles of Glucagon-Like Peptide-1 and Its Analogues in Dementia Targeting Impaired Insulin Secretion and Neurodegeneration. Degenerative neurological and neuromuscular disease, 12, 31–59. https://doi.org/10.2147/DNND.S247153
⁷Abdalla, M. A., Deshmukh, H., Atkin, S., & Sathyapalan, T. (2021). The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence. Therapeutic advances in endocrinology and metabolism, 12, 2042018821989238. https://doi.org/10.1177/2042018821989238
⁸Wegovy® approved by FDA for the treatment of adults with noncirrhotic MASH with moderate to advanced liver fibrosis. (2025, August 15). Prnewswire.com; Cision PR Newswire. https://www.prnewswire.com/news-releases/wegovy-approved-by-fda-for-the-treatment-of-adults-with-noncirrhotic-mash-with-moderate-to-advanced-liver-fibrosis-302531394.html
⁹Manalac, T. (Ed.). (2025, July 28). 5 Alzheimer’s Readouts To Watch. BioSpace. https://www.biospace.com/drug-development/5-alzheimers-readouts-to-watch
¹⁰Brooks, M. (2025, February 7). Despite Early Promise GLP-1 Disappoints in Parkinson’s Disease. Medscape. https://www.medscape.com/viewarticle/despite-early-promise-glp-1-disappoints-parkinsons-disease-2025a1000325
¹¹Amorim Moreira Alves, G., Teranishi, M., Teixeira de Castro Gonçalves Ortega, A. C., James, F., & Perera Molligoda Arachchige, A. S. (2025). Mechanisms of GLP-1 in Modulating Craving and Addiction: Neurobiological and Translational Insights. Medical Sciences, 13(3), 136. https://doi.org/10.3390/medsci13030136
¹²Zhou, L., Qu, H., Yang, L., & Shou, L. (2023). Effects of GLP1RAs on pregnancy rate and menstrual cyclicity in women with polycystic ovary syndrome: a meta-analysis and systematic review. BMC endocrine disorders, 23(1), 245. https://doi.org/10.1186/s12902-023-01500-5
¹³GLP-1 for PCOS: Impact on Ovarian Health and Metabolic Balance. (2025, April 29). Biology Insights. https://biologyinsights.com/glp-1-for-pcos-impact-on-ovarian-health-and-metabolic-balance/
¹⁴News, L. (2025, July 4). Swiss insurers fear cost explosion from weight loss drug. Le News. https://lenews.ch/2025/07/04/swiss-insurers-fear-cost-explosion-from-weight-loss-drugs/
¹⁵Gal, I. (2024, December 30). Wegovy weight loss shot cost to be subsidized | The Jerusalem Post. The Jerusalem Post | JPost.com. https://www.jpost.com/health-and-wellness/article-835391
¹⁶Constantino, A. K. (2025, January 8). Medicare can now cover Eli Lilly’s Zepbound for sleep apnea, Health Department agency says. CNBC. https://www.cnbc.com/2025/01/08/medicare-can-now-cover-eli-lillys-zepbound-for-sleep-apnea-cms-says.html?msockid=0c949fe3b07a6c1b334489acb1976d2d
¹⁷Noguchi , Y., & Wroth, C. (2024, March 22). Medicare plans can now cover Wegovy for patients at risk of heart disease. NPR. https://www.npr.org/sections/health-shots/2024/03/22/1240170094/wegovy-medicare-part-d-weight-loss-drugs