Autoimmune Reaction and Water Retention from GLP1s

[Stephen Matta, DO, MBA, CAQSM]

Hi everyone,

I’m reaching out to get your thoughts on a complex case I’m managing. I have a 55-year-old female patient presenting with water retention, difficulty losing weight, and suspected autoimmune reactions to GLP-1 agonists. Her history includes a single Depo-Provera injection at age 27, which I believe may have contributed to long-term metabolic and immune changes. She gained 25 lbs (from 105 to 130 lbs) within six months post-injection, a weight she’s maintained despite lifestyle efforts. She also has a history of fatty liver overgrowth. After semaglutide she developed a lupus like reaction include a facial rash and joint pain. She experienced joint pain and swelling also on tirzepatide.

Currently, she’s on retatrutide (which we just discontinued due to suspected water retention), CJC-1295/ipamorelin (100 mcg twice daily, also discontinuing), and testosterone pellets (provided by another provider). She’s also on estradiol patches and oral progesterone. Her diet is paleo with minimal processed foods, and she’s physically active with personal training, though weight loss remains elusive.

My assessment points to retatrutide as the likely cause of her water retention, possibly exacerbated by CJC-1295/ipamorelin, though I believe the latter is less likely to cause issues alone. I’ve discontinued retatrutide and CJC-1295/ipamorelin. I don’t think the peptides are contributing to her joint pain, as they tend to balance the immune system, which should help her autoimmunity. I suspect her Depo-Provera exposure may have led to insulin resistance, elevated insulin levels, and an autoimmune reaction affecting her glucose receptors, which could explain both her weight loss resistance and her reaction to GLP-1 agonists.

I’d greatly appreciate any insights or experiences you’ve had with similar cases, particularly regarding water retention with retatrutide, the interplay of growth hormone peptides with autoimmunity, or long-term effects of Depo-Provera on metabolism and immune function. Thanks in advance for your input!  Just as a side note, I’ve already tried to use artificial intelligence to figure this out.

Thanks.

Steve Matta

[jean berumen]

Hello,

I have had a couple of female patients that have not responded to GLP-1 treatments, which I suspect is likely due to underlying inflammation/autoimmune conditions. I have started them on LDN (Low Dose Naltrexone) therapy , which has significantly improved their overall energy levels and aided in weight loss. Since chronic inflammation is directly associated with insulin resistance, LDN therapy can aid in decreasing this, as well as overall inflammation. There are many benefits implementing  LDN in patients with autoimmune whether they have been diagnosed or not, LDN has shown promise in many disease processes. Below are a few highlights from one article/paper, although LDN has been used in Europe for decades, in US they still claim research to be in its “infancy”. It is worth a try, however patients on opiate therapy are not candidates for LDN therapy. There  are also articles specific to weight loss.

Low-dose naltrexone: A possible safe effective treatment for autoimmune disease and cancer

Anti-Aging Therapeutics, Volume 12, Chapter 3
January 2009:

Naltrexone is an opiate antagonist drug that has been used safely for 25 years in addiction medicine. Research has shown that in addition to its opiate antagonist properties at 50-300 mg per day dosages, it has immunoregulatory properties at dosages as low as 3.0 mg, Low dose naltrexone (LDN) improves the clinical state of patients with autoimmune diseases such as Crohn’s disease, rheumatoid arthritis, and multiple sclerosis. Another impressive property of LDN is its ability to arrest cancer cell growth. The remarkable fact is LDN can enhance the immune system for these two major disease classifications with little or no side effects.

This paper will describe the science behind LDNs physiological mechanisms to reduce the effects of autoimmune disease and inhibit cancer cell growth. 

There are also resources  available at  ldnresearchtrust.org

Implementing this can help with your patients joint pain as well, I find the LDN benefits most with significant improvement, unfortunately it does not benefit all.  Whether it be a compliance issue or underlying pathology, given the variables a specific cause in some may remain elusive.

Hope this helps, sorry for late reply I am new to the group, and exploring the site and members forum.

Jean Berumen

 

[Kristelle Reyes]

Hello @drstevemeetingpointhealth-com,

Here’s a video response from Dr. Seeds’ June 2025 Office Hours at 00:55. Please watch by clicking the link below:

https://ssrpinstitute.org/ssrp-members-videos/

Thank you! ?

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