Can GLP-1 Medications Be Considered for Weight Loss in Patients with APS?

The APS Program Community Q&A Series answers questions received from the APS Program community and covers a variety of topics.
Author: Yu (Ray) Zuo, MD, MSCS

I’m thrilled to introduce Lauren Shevell, MD, a hematologist specializing in conditions such as anemia, low platelet counts, abnormal bleeding, and blood clotting disorders, including antiphospholipid syndrome (APS). Dr. Shevell is an emerging leader in her field, gaining regional recognition for her clinical excellence. Our APS program is fortunate to collaborate with her, and together, we co-manage many APS patients. In this article, Dr. Shevell and I will explore what GLP-1 drugs are, how they work, and whether they are a safe option for people with APS.

If you’re living with APS, managing the ups and downs of this condition can be challenging. In addition to the ongoing concern about blood clots, symptoms like fatigue, headaches, joint pain, and brain fog can make daily life more challenging than you would like it to be. If you also struggle with obesity or metabolic syndrome, maintaining your health can feel even more overwhelming.

Recently, glucagon-like peptide-1 (GLP-1) receptor agonists - a class of medications originally developed to treat type 2 diabetes - have gained attention for their role in weight loss and possible effects on inflammation. But are these medications safe for people with APS, and do they offer any unique benefits or risks?

What are GLP-1 drugs?

GLP-1 receptor agonists are a class of medications primarily used to treat type 2 diabetes¹. These drugs mimic the glucagon-like peptide-1 (GLP-1) hormone, which helps regulate blood sugar by:

• Stimulating insulin release when blood sugar is high
• Reducing glucagon secretion (a hormone that increases blood sugar)
• Slowing digestion, leading to an increased sensation of fullness and weight loss

Some common GLP-1 medications include Dulaglutide (Trulicity), Liraglutide (Saxenda, Victoza), and Semaglutide (Mounjaro, Ozempic, Rybelsus, Wegovy).

Although originally designed for diabetes management, GLP-1 medications are now widely used for weight loss, even in people without diabetes. Certain GLP-1 drugs, such as semaglutide (Wegovy) and liraglutide (Saxenda), are FDA-approved for weight management in:

• People with a BMI ≥30 kg/m² (sometimes called “obesity”)
• People with a BMI ≥27 kg/m² (overweight) with at least one weight-related condition (e.g., high blood pressure, high cholesterol, or sleep apnea)

Are GLP-1 drugs safe for people with APS?

For people with APS, the big question is whether these medications are safe, especially when used alongside anticoagulation therapy. Some detailed questions and answers follow.

Do GLP-1 drugs increase the risk of blood clots?

Current evidence suggests that GLP-1 receptor agonists do not increase the risk of thrombosis (blood clots) and may even offer some protection from thrombosis development in certain situations. Large cardiovascular trials, such as LEADER (liraglutide), SUSTAIN-6 (semaglutide), and REWIND (dulaglutide), found that these drugs actually reduced the risk of major heart problems like heart attacks and strokes in people with diabetes^{2, 3}. Importantly, they did not find an increased risk of deep vein thrombosis (DVT) or pulmonary embolism (PE), which are common concerns in APS.

Additional studies have confirmed that GLP-1 drugs do not appear to raise blood clot risk and may even protect the heart and blood vessels by improving blood flow and reducing inflammation^{2, 3}. Furthermore, individuals with diabetes who were treated with GLP-1 drugs were less likely to develop blood clots than those who used another medication class to treat diabetes. The two study populations were well matched in terms of other risk factors for blood clots, including body mass index and hemoglobin A1c (a measure of diabetes severity).⁷

Although rare cases of blood clots have been reported in people taking GLP-1 drugs, these were mostly linked to underlying risk factors like obesity or immobility, not the medication itself. Regulatory agencies like the FDA and EMA have not raised any safety concerns about blood clot risk with GLP-1 drugs. While no research has specifically studied GLP-1 drugs in APS patients, there is no current evidence to suggest that they increase the risk of blood clots.

Do GLP-1 drugs worsen autoimmune diseases?

No evidence exists that GLP-1 receptor agonists worsen autoimmune diseases, but we must acknowledge that research is still limited. In fact, some studies have suggested that GLP-1 drugs actually have anti-inflammatory properties. Having said that, one 2023 case report described a patient developing drug-induced lupus after taking semaglutide⁴. This condition, caused by certain medications like the blood pressure medication hydralazine, can mimic systemic lupus erythematosus (SLE) with symptoms like joint pain, fever, and fatigue. While drug-induced lupus usually resolves after stopping the medication, it’s an important consideration for people already living with lupus or other autoimmune diseases. 

Acknowledging that this is an area where more research is needed, we tend to think GLP-1 medications will be tolerated well in most patients with autoimmune diseases. Of course, it’s always best to discuss the risks with your doctor if you have an autoimmune condition and are considering GLP-1 therapy.

Do GLP-1 drugs interact with warfarin (Coumadin)?

GLP-1 drugs do not have a direct interaction with warfarin, but they can indirectly affect how well warfarin works.

• Slower Digestion: GLP-1 drugs slow digestion, which could slightly delay warfarin absorption, though this is usually not a major issue
• Weight Loss & Diet Changes: Losing weight and eating differently may affect INR levels, which measure how well warfarin is working

One recent study evaluated whether starting a GLP-1 would impact how well warfarin worked, and the results were presented at the 2024 American Society of Hematology’s Annual Meeting⁵. Researchers reviewed medical records from a single center between 2008 and 2023 to assess the impact of GLP-1 receptor agonists on warfarin therapy in 28 patients who had routine INR testing before and after starting a GLP-1 drug. The study found that, on average, INR stability remained unchanged, with patients spending 59% of the time in the desired INR range before GLP-1 therapy and 60% after. So, there was no real difference. No patients experienced major bleeding events. The study did find that a small number of patients who previously had very stable INR control saw a slight decrease in their stability after starting GLP-1 therapy, though without any serious complications.

Overall, the findings suggest that GLP-1 drugs can be safely used with warfarin, but careful monitoring is still recommended. Given the study’s small size and single-center design, further research is needed to confirm these results in a larger population.

If you take warfarin and start a GLP-1 drug, your doctor will likely want to monitor your INR more closely at first. Watch for signs of bleeding (bruising, nosebleeds) or clotting (leg swelling, chest pain, shortness of breath) and report any major dietary or weight changes.

Do GLP-1 drugs interact with any other common APS medications?

Many APS patients take additional immunomodulatory medications, such as hydroxychloroquine (Plaquenil), which helps protect blood vessels and reduce clotting risk.

• Hydroxychloroquine & GLP-1 drugs: Micromedex, a widely used clinical database, suggests that combining these two drugs may slightly increase the risk of low blood sugar. This does not mean they should never be used together, just that monitoring is recommended
• Other APS medications: Drugs like low-dose aspirin, mycophenolate, methotrexate, and rituximab do not show significant interactions with GLP-1 drugs

Potential benefits of GLP-1 drugs for APS patients

GLP-1 drugs offer several potential benefits that may make them a valuable option for APS patients with coexisting conditions like diabetes or obesity. For individuals living with both APS and type 2 diabetes, maintaining stable blood sugar levels is crucial, as poor glucose control can increase the risk of cardiovascular disease - something we are already worried about in people with lupus and APS. GLP-1 drugs help regulate blood sugar, potentially reducing the risk of diabetes-related complications^{1, 6}.

Additionally, weight loss is another key advantage, as obesity can significantly amplify chronic inflammation, which may worsen APS symptoms. By promoting weight loss, GLP-1 medications might help lower inflammation and improve overall health.

Emerging research also suggests that these drugs may have mild anti-inflammatory effects, which could further benefit individuals with inflammatory conditions^{1, 6}.

In summary, GLP-1 drugs are primarily used for diabetes and weight loss, but they do not appear to increase blood clotting risk and have no major interactions with warfarin. While data on their use in APS patients is limited, they may offer potential benefits for those with coexisting metabolic conditions. If you have APS and are considering a GLP-1 medication, talk to your doctor to weigh the potential risks and benefits based on your unique health needs. With careful monitoring and a personalized approach, these medications could be a valuable tool in managing your overall health!

References

1. Moore PW, Malone K, VanValkenburg D, et al. GLP-1 Agonists for Weight Loss: Pharmacology and Clinical Implications. Adv Ther. Mar 2023;40(3):723-742. doi:10.1007/s12325-022-02394-w

2. Ussher JR, Drucker DJ. Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action. Nat Rev Cardiol. Jul 2023;20(7):463-474. doi:10.1038/s41569-023-00849-3

3. Marx N, Husain M, Lehrke M, Verma S, Sattar N. GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients With Type 2 Diabetes. Circulation. Dec 13 2022;146(24):1882-1894. doi:10.1161/CIRCULATIONAHA.122.059595

4. Castellanos V, Workneh H, Malik A, Mehta B. Semaglutide-Induced Lupus Erythematosus With Multiorgan Involvement. Cureus. Mar 2024;16(3):e55324. doi:10.7759/cureus.55324

5. Kisala PAMAAUS. Warfarin and GLP-1 Receptor Agonist Interaction Effects on Time in Therapeutic Range. presented at: Blood (2024) 144 (Supplement 1): 5579; 2024

6. Sandsdal RM, Juhl CR, Jensen SBK, et al. Combination of exercise and GLP-1 receptor agonist treatment reduces severity of metabolic syndrome, abdominal obesity, and inflammation: a randomized controlled trial. Cardiovasc Diabetol. Feb 25 2023;22(1):41. doi:10.1186/s12933-023-01765-z

7. Cho Han Chiang, Soravis Osataphan, Yu-Cheng Chang, Yu-Che Lee, Ko-Yun Chang, Cho-Hung Chiang, Mandy N. Lauw, Kenneth A Bauer, Dhruv S. Kazi, Rushad Patell; Glucagon-like Peptide 1 Receptor Agonists Reduce the Risk of Venous Thromboembolism in Patients with Diabetes Irrespective of Obesity: A Propensity Score-Matched Multicenter Database Analysis. Blood 2024; 144 (Supplement 1): 701

Guest Author: Lauren Shevell, MD

Dr. Lauren Shevell is a hematologist specializing in non-cancerous blood disorders, including anemia, thrombocytopenia, bleeding, and clotting disorders, including antiphospholipid syndrome. She earned her medical degree from Rosalind Franklin University, completed her internal medicine residency at Yale University, and pursued her hematology fellowship at the University of Michigan. She is double board-certified in internal medicine and hematology. Dr. Shevell's clinical interests include the diagnosis and management of complex hematological conditions, with a particular focus on hemostasis and thrombosis. Her research interests center on investigating new therapies for hematologic conditions and understanding the uptake of novel therapies. Outside of medicine, Dr. Shevell enjoys going on adventures with her husband and son, both locally and internationally.

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