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The Potential for GLP-1s in the Treatment of Rheumatoid Arthritis

Medically Reviewed By Alexandra Perez, PharmD, MBA, BCGP

Researchers are exploring the potential benefits of glucagon-like peptide 1 (GLP-1) analogs on various diseases, including rheumatoid arthritis (RA).

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The Food and Drug Administration (FDA) approved the use of GLP-1 analogs for some people as a weight loss treatment for obesity. Other names for GLP-1 analogs include GLP-1 agonists, GLP-1 receptor agonists, and incretin mimetics. Here’s a look at early research into how they might work to treat RA.

Exploring glucagon-like peptide 1

Glucagon-like peptide 1 (GLP-1) is an incretin hormone Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source . Initially studied in type 2 diabetes, it can help stimulate insulin release in the gut in response to food. Other GLP-1 effects include:

In people with type 2 diabetes, these GLP-1 effects can be muted or totally absent. GLP-1 analogs can help restore the insulin-glucagon balance in these people by mimicking the hormone.

A noticeable side effect of GLP-1 analogs in type 2 diabetes treatment is weight loss. Noticing this led researchers to study and approve GLP-1 analogs to treat obesity in people with or without diabetes. People using them for this purpose may lose more than 10–15% Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source  of their body weight. 

Researchers studying GLP-1 found receptors for the hormone throughout the body, not just in the gut. GLP-1 seems to have widespread effects on various organ systems, including these:

  • cardiovascular
  • respiratory
  • nervous
  • skeletal

One of the GLP-1 effects on these systems is inflammation reduction, a key process involved in many diseases, including RA.

Research on GLP-1 analogs for rheumatoid arthritis 

A 2021 research review showed a potential link between inflammatory arthritis forms and metabolic irregularities involving insulin. Also, there might be a link between insulin resistance and RA disease activity. This has led researchers to study how the following glucose-lowering medications may treat RA:

  • dipeptidyl peptidase-4 inhibitors
  • GLP-1 analogs
  • metformin
  • thiazolidinediones

A 2024 review involved three preclinical studies examining how GLP-1 analogs can treat RA. The preclinical studies showed that GLP-1 analogs may have various anti-inflammatory effects on human fibroblast-like synoviocytes. These dose-dependent effects include reductions in:

  • inflammatory pathway activations
  • proinflammatory cytokine and collagen degradation enzyme expressions
  • mitochondrial dysfunction
  • oxidative stress

According to the above review, all three studies highlighted that GLP-1 analogs may work to treat RA by inhibiting the nuclear factor kappa-light-chain-enhancer of activated B cells pathway, which can improve immune responses.

However, preclinical research may only sometimes pan out in human studies. Research on GLP-1 analogs treating RA in humans is limited but promising.

The review also involved two studies examining how the drug liraglutide may treat RA. Both described improvements in Disease Activity Score 28, a scoring system that can help experts rate RA disease activity and treatment responses.

Early study results may support further research into how GLP-1 analogs might treat RA. More studies with larger populations are necessary to fully understand whether these drugs have a place in RA treatment.

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  1. Collins L, et al. (2023). Glucagon-like peptide-1 receptor agonists. https://www.ncbi.nlm.nih.gov/books/NBK551568/
  2. Jensterle M, et al. (2022). Efficacy of GLP-1 RA approved for weight management in patients with and without diabetes: A narrative review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9063254/
  3. Karacabeyli D, et al. (2024). Glucagon-like peptide 1 receptor agonists in patients with inflammatory arthritis or psoriasis: A scoping review. https://journals.lww.com/jclinrheum/fulltext/2024/01000/glucagon_like_peptide_1_receptor_agonists_in.5.aspx
  4. Klausen MK, et al. (2022). The role of glucagon‐like peptide 1 (GLP‐1) in addictive disorders. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820218/
  5. Mehdi SF, et al. (2023). Glucagon-like peptide-1: A multi-faceted anti-inflammatory agent. https://www.frontiersin.org/articles/10.3389/fimmu.2023.1148209/full
  6. Tejera-Segura B, et al. (2017). Incretins in patients with rheumatoid arthritis. https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-017-1431-9
  7. Tripolino C, et al. (2021). Insulin signaling in arthritis. https://www.frontiersin.org/articles/10.3389/fimmu.2021.672519/full

Medical Reviewer: Alexandra Perez, PharmD, MBA, BCGP
Last Review Date: 2023 Dec 20
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