Semaglutide – the Surprising New Anti-Fibrosis Drug

Disclaimer: The information provided in this blog in not intended to be medical advice. Always consult your doctor before taking a new medication.

You’ve probably heard about the wonder drugs, Ozempic and Wegovy, which are taken by millions of people worldwide to treat diabetes and obesity. The amazing health benefits of semaglutide - the drug in these medications - are well established for people with diabetes or obesity, with numerous clinical trials demonstrating that it’s safe and highly effective. But the news keeps getting better, with recent clinical trials in a wide range of chronic (long-term) conditions suggesting significant treatment benefits even when patients are normal weight and not diabetic. Now, semaglutide looks set to transform almost every area of medicine. These surprising benefits appear to be due to the potent anti-inflammatory and anti-fibrotic effects of semaglutide [1] on the whole body, with systemic reductions in oxidative stress and inflammatory cytokines [2] (the signalling molecules the body makes). And a growing body of evidence indicates that many of semaglutide’s anti-inflammatory and anti-fibrosis actions are independent of blood sugar improvements and weight-loss [1,3], greatly expanding the potential to help non-obese people who have a chronic condition.

Clinical trials with semaglutide have demonstrated significant potential to treat diseases of the brain, liver, heart, vascular system (veins and arteries), lungs, bones, skin, and kidneys [1,4], and this class of drugs also shows promise for treating arthritis [1,5]. The benefits to health have led to the approval of semaglutide for treating kidney and heart fibrosis in the US, but the treatment potential is much wider, opening possibilities for treating cancer, psoriasis, polycystic ovary syndrome, sinus disease, obstructive sleep apnoea, Alzheimer’s, Parkinson’s, liver disease, atherosclerosis (vascular disease) [6], asthma, some forms of nerve damage [2] and more. This news has created a sub-culture of off-label semaglutide micro-dosing (staying on, or near, the starting dose) by people with a variety of chronic conditions.

Does semaglutide have potential for treating arthrofibrosis? Given the promising research in organ fibrosis and the reduction in chronic low-grade inflammation and joint fibrosis in arthritis [1], I think this is likely, but research is needed.

In arthrofibrosis, osteoarthritis and rheumatoid arthritis, fibrosis of the synovial lining (lining around joints) can occur, creating inflammation, pain and restricted joint mobility [1,7]. So, although osteoarthritis and rheumatoid arthritis are different in some aspects of their pathology, treatments for these diseases may benefit arthrofibrosis patients. Clinical and pre-clinical osteoarthritis research suggests that semaglutide reduces pain scores and cartilage loss over 2 years, compared to placebo [1], and pre-clinical research showed that a similar drug (liraglutide) reduced fibrosis of the joint synovium and reduced pain severity, despite no difference in weight-loss compared to the control groups [1].

Figure from Jones 2026 [1]. Summary of preclinical and clinical evidence for the anti-fibrotic potential of semaglutide and similar drugs across organ systems.

So, how does semaglutide do all these surprising things? Semaglutide belongs a class of drugs called glucagon-like peptide-1 receptor agonists (GLP-1RAs) that mimic GLP-1 protein produced naturally by our bodies. GLP-1 is a hormone that regulates insulin, makes people feel full for longer, and decreases blood sugar levels, but it turns out it does much more than this. GLP-1RAs remain active for much longer than the natural form, and are powerful suppressors of inflammation and fibrosis [1,8], regulating immune cells and inflammatory pathways [9]. The binding of GLP-1RAs to cell receptors has both direct and indirect anti-inflammatory and anti-fibrotic effects, reducing inflammatory cytokines and the accumulation of immune cells and suppressing fibrotic signalling pathways including the key fibrosis factor, TGF-β1. GLP-1 receptors are present in much of the body, including in joint cartilage and synovium [10]. There are a number of drugs available in the GLP-1RA class, such as liraglutide, but semaglutide is the best-known and most widely used [2] and can demonstrate more effective treatment outcomes [6].

It appears that GLP-1RAs, such as semaglutide, can reduce inflammation and fibrosis in joints, with disease-modifying and pain-reducing outcomes [1].

Semaglutide counteracts an unhealthy type of metabolism that is created by chronic conditions, and makes more energy available for the brain and muscles. However, in addition to the frequent headlines about the health benefits of semaglutide, there have also been concerns raised about potential negative side-effects, with suggestions of an increased risk of pancreatitis and loss of bone, vision and muscle. However, these claims have recently been discounted. A meta-analysis of 80 000 patients found “GLP-1 RAs were not associated with an increased risk of optic nerve/vision-threatening events” [11], and a recent clinical trial of people taking the highest dose of semaglutide demonstrated excellent safety, increased muscle strength and an increased ratio of lean mass relative to total body mass in people taking semaglutide [12]. This, together with research in animals, suggest that semaglutide may improve muscle quality, and could potentially protect against muscle atrophy (loss) [12,13]. However, it’s well known that weight-loss from dieting is associated with muscle and bone loss because of reduced mechanical loading. Studies suggest that GLP-1RAs don’t adversely affect bone mineral density and may be associated with a reduced risk of fractures [14]. But more clinical trials are needed, especially in patients that don’t have diabetes or obesity.

I believe we need a clinical trial to determine if semaglutide significantly reduces the risk of arthrofibrosis returning after surgery, beginning treatment before surgery and continuing for three months post-op.

Research from the Yale School of Medicine suggests that for people with diabetes, taking semaglutide for two to 3-months before a total knee replacement significantly reduces infections and all other severe and minor postoperative complications [15]. It seems that 4 to 5 weeks of semaglutide use is required for clinical efficacy [15]. Semaglutide has also been reported to improve outcomes of surgically repaired tendons in people with diabetes [16]. Semaglutide may also help manage symptoms in people who have chronic arthrofibrosis; however, weight-bearing activities are likely to remain painful when the Hoffa’s fat pad is fibrotic and impinged (pinched) by the bones of the knee, as this regular insult will maintain fibrosis (see “Hoffa’s fat pad”). Semaglutide is sometimes used in combination with metformin, increasing the anti-inflammatory and anti-fibrotic effects [2,8], and significantly improving liver inflammation and fibrosis in people with non-alcoholic fatty liver disease [8].

I’m excited to see what the future holds for GLP-1 drugs. The successes GLP-1RAs have prompted an enormous surge in research, with new drug developments and clinical trials in an ever-expanding range of conditions. However, it’s important to note that at this stage, GLP-1 RAs should not be thought of as a cure for arthrofibrosis (or any form of fibrosis).

Side-effects and Considerations

• Common side effects of semaglutide include gastrointestinal upset such as constipation and diarrhea. These side-effects are typically short-lived and manageable as body becomes accustomed to the medication [8] and in most cases are dose-dependent [4]. However, people with significant gastrointestinal disease may not be able to take this drug [4]. Clinicians often advise patients to “start low and go slow”, meaning people should only increase the dose as needed. Please consult your doctor to check for drug interactions and contraindications.

• Because semaglutide slows the emptying of stomach contents, some hospitals require patients to stop semaglutide treatment prior to surgery to reduce the risk of aspiration (inhaling vomit) as the patient wakes up. However, recent guidelines indicate that only patients identified as high risk should stop semaglutide a week before surgery [15].

• Food intake is reduced by semaglutide, and although research shows people taking it purchase fewer highly processed, sugary foods and instead buy more protein (and fruit and veg), some people may need to consume a high-quality protein supplement after the final meal of the day.

• People who are not diabetic or overweight may find it difficult to get semaglutide prescribed, and it may be expensive.

• Obese people who lose a lot of weight rapidly can develop facial drooping. Semaglutide can cause what is known as “Ozempic face” from the loss of fat in the face.

  
  

References

1. Simon, W. J. The Anti-Fibrotic Potential of GLP-1 and GIP Receptor Agonists in Chronic Inflammatory Disorders: Mechanisms and Therapeutic Horizons. Fibrosis 4, 10001–10001 (2026). https://doi.org/10.70322/fibrosis.2026.10001

2. Petkovic-Dabic, J. et al. Effects of Semaglutide Treatment on Psoriatic Lesions in Obese Patients with Type 2 Diabetes Mellitus: An Open-Label, Randomized Clinical Trial. Biomolecules 15 (2025). https://doi.org/10.3390/biom15010046

3. Wong, C. K. & Drucker, D. J. Antiinflammatory actions of glucagon-like peptide-1-based therapies beyond metabolic benefits. J Clin Invest 135 (2025). https://doi.org/10.1172/JCI194751

4. Ros-Madrid, I., Cano-Marmol, R., Ferrer-Gomez, M. & Ramos-Molina, B. Anti-inflammatory properties of GLP-1 receptor agonists and other ancillary benefits from a pharmacological perspective. Can J Physiol Pharmacol 103, 369–377 (2025). https://doi.org/10.1139/cjpp-2025-0148

5. Yang, Y. et al. Osteoarthritis treatment via the GLP-1-mediated gut-joint axis targets intestinal FXR signaling. Science 388, eadt0548 (2025). https://doi.org/10.1126/science.adt0548

6. Zarei, M., Sabetkasaei, M., Mozafari, M. & Zaeri, S. The expanding role of semaglutide: beyond glycemic control. J Diabetes Metab Disord 24, 160 (2025). https://doi.org/10.1007/s40200-025-01663-z

7. Bhamidipati, K. et al. Spatial patterning of fibroblast TGFbeta signaling underlies treatment resistance in rheumatoid arthritis. Nat Immunol (2026). https://doi.org/10.1038/s41590-025-02386-2

8. Ren, R., Pei, Y., Kong, L. & Shi, Y. The effect of semaglutide combined with metformin on liver inflammation and pancreatic beta-cell function in patients with type 2 diabetes and non-alcoholic fatty liver disease. J Diabetes Complications 39, 108932 (2025). https://doi.org/10.1016/j.jdiacomp.2024.108932

9. Jamal, N., Hollabaugh, W., Scott, L. & Takkouche, S. Unravelling the ties that bind: The intersection of obesity, osteoarthritis, and inflammatory pathways with emphasis on glucagon-like peptide-1 agonists. Clin Obes 15, e12700 (2025). https://doi.org/10.1111/cob.12700

10. Meurot, C. et al. Liraglutide, a glucagon-like peptide 1 receptor agonist, exerts analgesic, anti-inflammatory and anti-degradative actions in osteoarthritis. Scientific Reports 12 (2022). https://doi.org/10.1038/s41598-022-05323-7

11. Li, H.-Y. et al. GLP-1 Receptor Agonists and Risk of Optic Nerve or Vision-Threatening Events in Patients With Type 2 Diabetes or Cardiometabolic Diseases: A Meta-analysis of Randomized Controlled Trials. Diabetes Care (2026). https://doi.org/10.2337/dc25-1929

12. Alissou, M. et al. Impact of Semaglutide on fat mass, lean mass and muscle function in patients with obesity: The SEMALEAN study. Diabetes Obes Metab 28, 112–121 (2026). https://doi.org/10.1111/dom.70141

13. Samajdar, S. S. & Joshi, S. Semaglutide beyond weight loss: Mechanistic insights and functional paradoxes from the SEMALEAN study. Diabetes Obes Metab 28, 779–781 (2026). https://doi.org/10.1111/dom.70242

14. Hansen, M. et al. Local administration of insulin-like growth factor-I (IGF-I) stimulates tendon collagen synthesis in humans. Scand J Med Sci Sports 23, 614–619 (2013). https://doi.org/10.1111/j.1600-0838.2011.01431.x

15. Seddio, A. E. et al. As Few as Three Months of Preoperative Semaglutide Exposure Prior to Total Knee Arthroplasty Is Associated With Reduced Postoperative Adverse Events in Patients Who Have Type II Diabetes. J Arthroplasty 40, 3089–3096.e3081 (2025). https://doi.org/10.1016/j.arth.2025.08.003

16. Seddio, A. E. et al. Lower Risk of Postoperative Complications and Rotator Cuff Retear Associated With Semaglutide Use in Patients with Type II Diabetes Mellitus Undergoing Arthroscopic Rotator Cuff Repair. Arthroscopy 41, 199–206 (2025). https://doi.org/10.1016/j.arthro.2024.09.057