Evidence Against Using Oral Semaglutide in Arthritis
Oral semaglutide should be used with caution in patients with arthritis due to potential gastrointestinal adverse effects and a reported case of GLP-1 receptor agonist-induced polyarthritis, though recent evidence suggests potential benefits for knee osteoarthritis patients with obesity.
Concerns with GLP-1 Receptor Agonists in Arthritis
Reported Adverse Effects
- There is a documented case report of bilateral, symmetrical, seronegative polyarthritis associated with liraglutide (a GLP-1 receptor agonist), which resolved within one week after discontinuation of the medication 1
- The most common adverse effects of semaglutide are gastrointestinal disturbances including nausea, vomiting, diarrhea, constipation, and abdominal pain, which could potentially exacerbate discomfort in arthritis patients 2, 3
- Semaglutide may increase the risk of gallstones and cholecystitis, which could complicate management of patients with arthritis who may already be on multiple medications 2
Medication Interactions
- Patients with arthritis often take multiple medications for pain management and inflammation control, which could potentially interact with semaglutide 4
- The American College of Rheumatology guidelines for osteoarthritis management do not specifically address GLP-1 receptor agonists, suggesting limited evidence for their use in this population 4
- Semaglutide may delay gastric emptying, which could affect the absorption of oral medications commonly used for arthritis management 4
Recent Evidence Supporting Use in Specific Arthritis Populations
Benefits in Knee Osteoarthritis with Obesity
- A recent 2024 randomized controlled trial (STEP 9) demonstrated that once-weekly injectable semaglutide (2.4 mg) significantly reduced both body weight (-13.7% vs -3.2% with placebo) and knee osteoarthritis pain in patients with obesity 5
- The STEP 9 trial showed significant improvement in WOMAC pain scores (-41.7 points with semaglutide vs -27.5 points with placebo) and physical function in patients with knee osteoarthritis and obesity 5
- A 2023 study found that semaglutide use in patients undergoing total knee arthroplasty was associated with lower odds of prosthetic joint infections (2.1% vs 3.0%) and hospital readmissions (7.0% vs 9.4%) 6
Potential Risks in Surgical Patients
- The same 2023 study found that semaglutide use in total knee arthroplasty patients was associated with higher incidence of myocardial infarction (1.0% vs 0.7%), acute kidney injury (4.9% vs 3.9%), pneumonia (2.8% vs 1.7%), and hypoglycemic events (1.9% vs 1.2%) 6
- Careful monitoring is recommended if semaglutide is used in patients with diabetes who are at risk for deterioration of existing diabetic retinopathy, which could be relevant for arthritis patients with comorbid diabetes 3
Clinical Considerations for Use
Dosing and Administration
- If semaglutide is used in arthritis patients, gradual dose titration is recommended to minimize gastrointestinal adverse effects 4
- For oral semaglutide, the recommended starting dose is lower than the maintenance dose, with gradual titration to improve tolerability 4
- Patients should be monitored for potential adverse effects, particularly gastrointestinal symptoms, which are the most common reason for discontinuation 5, 3
Cost-Effectiveness
- A 2025 cost-effectiveness analysis found that both tirzepatide and semaglutide would be considered cost-effective compared to usual care for patients with knee osteoarthritis and obesity 7
- For patients with knee osteoarthritis and obesity who are eligible, bariatric surgery may provide greater health benefits at lower costs than GLP-1 receptor agonists 7
Monitoring Recommendations
- Monitor for signs of polyarthritis in patients starting semaglutide, particularly in the first few months of treatment 1
- Regular assessment of gastrointestinal symptoms is important, as these are the most common adverse effects and may lead to discontinuation 3
- In patients with diabetes and arthritis, monitor for potential hypoglycemia if the patient is also on insulin or insulin secretagogues 4
- Monitor for gallbladder disease, which has been reported with semaglutide use 2, 3