Semaglutide/Tirzepatide: Beyond Weight Loss
GLP-1 (glucagon-like peptides 1 such as Semaglutide, active ingredient in Ozempic, Wegovy) and dual GLP-1/GIP (gastric inhibitory polypeptide such as Tirzepatide, active ingredient in Mounjaro, Zepbound) are mostly known for their effects on insulin resistance, blood sugar and weight loss. But they in fact offer way more benefits for the body.
Dr. Dominique Fradin-Read is pleased to share the following:
Treatments that have already been extensively tested in clinical trials and approved by the FDA
Upcoming indications currently under research, showing highly promising preliminary results
Neuroprotective Mechanisms
We already have good clinical evidence supporting these neuroprotective effects:
A large-scale study involving over 5 million obese adults found that GLP-1 receptor agonists were associated with a significantly lower risk of developing Alzheimer's, Lewy body dementia, and vascular dementia. Semaglutide, in particular, showed the most pronounced protective effects.
Preclinical studies indicate that these drugs can reduce inflammation following a stroke, even when administered up to 24 hours post-stroke.
Animal models suggest that GLP-1receptor agonists may improve myelination and reduce neuroinflammation and oxidative stress in multiple sclerosis, though clinical trials are needed to confirm these effects.
For Tirzepatide specific brain studies are still in early stages. The peptide is a dual agonist as described above working on the GIP receptors on top of the GLP1 receptors. Tirzepatide role in the brain needs to be more studied but its dual action suggests that the peptide might have synergistic benefits on brain health. It may have even stronger neuroprotective action than Semaglutide. A study evaluating the benefits of Tirzepatide on early Alzheimer patients is on its way at Loma Linda university.
Mood-related effects have also been observed with Tirzepatide use. Diabetic patients taking the medication were found to be 65% less likely to develop depression and 60% less likely to experience anxiety, suggesting a potential protective effect—possibly linked to improved metabolic health and weight loss. However, some individuals have reported adverse mental health effects while on Tirzepatide, including symptoms of depression and anxiety.
Both agents exert several neuroprotective effects:
Reduction of Neuroinflammation
Enhancement of Neurovascular Function
Promotion of Neurogenesis and Synaptic Plasticity.
Protection Against Neurodegeneration
While current findings are promising, further research is essential to fully understand the neuroprotective mechanisms of these treatments and their potential applications in treating neurodegenerative diseases. Clinical trials are underway to explore their efficacy in conditions such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis.
Cardiovascular Benefits
Semaglutide has demonstrated significant cardiovascular benefits in recent clinical studies, extending its therapeutic potential beyond diabetes and obesity management.
Key Cardiovascular Findings from Recent Studies
SELECT Trial: In a large-scale trial involving over 17,000 adults with cardiovascular risk factors, Semaglutide reduced the incidence of major adverse cardiovascular events (MACE)—including heart attack, stroke, and cardiovascular death—by 20% compared to placebo. Notably, these benefits were observed regardless of participants' baseline weight or the amount of weight lost during the study .
Oral Semaglutide Cardiovascular Outcomes: A study presented at the American College of Cardiology's Annual Scientific Session found that oral Semaglutide reduced the risk of cardiovascular death, heart attack, or stroke by 14% over four years.
Heart Failure and Kidney Disease Substudies: Additional analyses revealed that Semaglutide also benefits individuals with heart failure and chronic kidney disease. In these high-risk populations, Semaglutide reduced the risk of heart failure events and cardiovascular death, underscoring its potential in managing complex cardiometabolic conditions
This protective effect is attributed to several mechanisms that promote heart health, including:
Decreased inflammation
Enhanced endothelial function
Lowered blood pressure
Decrease body weight
Tirzepatide has a similar mechanism of action with added benefits due to its dual target on two receptors. This may further improve insulin sensitivity and fat metabolism. Tirzepatide has been shown to significantly reduce liver fat content, as demonstrated by proton density fat fraction (PDFF) studies, leading to improved liver function and favorable effects on cholesterol levels.
While full cardiovascular outcomes for Tirzepatide are not yet available, the preliminary data are very promising.
Bone Health Support: Osteoporosis and Osteoarthritis
GLP-1 receptors are found in bone tissue, suggesting a direct role in bone metabolism.
Preliminary data indicate that GLP-1 may also influence joint health. For example, Semaglutide has been associated with a 16% reduced risk of developing osteoarthritis in individuals with obesity. This is partly due to weight loss, but also to the anti-inflammatory effects of these peptides, which support joint health and enhance the ability to engage in physical activity.
Tirzepatide’s impact on inflammatory cytokine modulation may play a protective role in bone health (Hassan et al., 2024).
Theoretical mechanisms include:
Decreased bone resorption: GLP-1 may inhibit osteoclast activity, reducing bone breakdown.
Increased bone formation: Some studies show GLP-1 promotes osteoblast activity.
GLP-1 and GIP pathways help reduce inflammation, which is beneficial in conditions like osteoporosis where chronic inflammation contributes to bone resorption.
General Anti-Inflammatory Effects and More
Emerging research indicates that these medications also possess significant systemic anti-inflammatory properties, offering potential therapeutic benefits beyond their conventional uses.
Several mechanisms are underpinning this anti-Inflammatory effect:
Immune Cell Modulation:
These medicines can change how immune cells behave. They help reduce harmful substances in the body called pro-inflammatory cytokines (like TNF-alpha, IL-6, and IL-1β), which are often high in autoimmune diseases.
At the same time, they can increase helpful anti-inflammatory signals, like IL-10, which help calm the immune system.
NF-κB Pathway Inhibition and AMPK Signaling Activation:
GLP-1 and GLP1/ GIP medicines can turn off a key “inflammation switch” in the body called the NF-κB pathway. This pathway controls many of the genes that cause inflammation.
These medicines also activate a natural “helper” in the body called AMPK.
By acting on these pathways, both Semaglutide and Tirzepatide help reduce inflammation by stopping the production of harmful chemicals that cause swelling and pain.
These actions help the body keep a healthy balance between metabolism and inflammation.
Reduction in Inflammatory Biomarkers:
Clinical studies have demonstrated that GLP-1 medications significantly lower levels of C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-αwhile increasing adiponectin levels, indicating a reduction in general systemic inflammation.
Potential Benefits in Autoimmune Conditions
GLP-1 agonists like Semaglutide and dual GIP/GLP-1 agonists like Tirzepatide may offer immune-modulating and anti-inflammatory benefits that could help people with autoimmune diseases. However, more research is needed to confirm their role in treating or preventing these conditions.
Benefits for PCOS patients
Both Semaglutide and Tirzepatide are medications that primarily help with weight loss and insulin resistance, which are common issues in women with PCOS.
Improved Insulin Sensitivity
Semaglutide and Tirzepatide both help improve insulin sensitivity, meaning your body can use insulin more effectively. Since many women with PCOS have insulin resistance, these medications can help reduce blood sugar levels and lower insulin levels, improving overall metabolic health.
Weight Loss
Weight gain is a common issue in PCOS. Semaglutide and Tirzepatide are both effective in promoting weight loss. Losing weight can help improve insulin sensitivity, reduce androgens (male hormones), and may lead to better menstrual regularity.
Menstrual Regularity
By improving insulin sensitivity and helping with weight loss, these medications can help regulate menstrual cycles, which is often a challenge for women with PCOS due to hormonal imbalances.
Improved Fertility
Since weight loss and better insulin control are important for fertility in PCOS patients , these medications may help improve chances of pregnancy by addressing these issues.
While early studies and clinical experiences are promising, these medications are not yet FDA-approved specifically for PCOS. Research on how they work for PCOS-related symptoms is still ongoing.
Conclusion
Beyond their metabolic effects, Semaglutide and Tirzepatide anti-inflammatory properties suggest potential therapeutic applications in conditions characterized by chronic inflammation, such as cardiovascular diseases, neurodegenerative disorders, bone degenerative disease and autoimmune conditions. These peptides could be considered as potential “anti-aging agents.”
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Important Warning
In addendum to the information above, Dr. Dominique Fradin-Read would like to warn her patients of a growing public health issue and a real threat for all patients in the United States.
In addition to legitimate products produced by pharmacies under the Department of Health oversight, many so-called “laboratories" are recruiting doctors to sell research-grade peptides. These entities are not subject to the stringent quality control, safety standards, or regulatory oversight required for legitimate medications. These "laboratories" are not required to spend $1 million on a cleanroom like pharmacies, many use virtual office addresses and don't have a physical location. They are able to import research vials in bulk, unaware of the manufacturing conditions. Research published by Ashraf et al. showed purity of laboratory peptides ranging from 7.7% to 14.37% in samples tested, indicating significant levels of impurities.
Even more concerning is that some physicians are now private-labeling and distributing these laboratory injectables, placing their office's own label directly on the vials.
Equally frightening is the fact that some websites are marketing and selling these products directly to the public. These websites are extremely misleading and the information “for research purpose only -not for human use- or not to be distributed as a dietary supplement” is often dissimulated, written in very small letters, on the bottom of a picture of the bottle after pages of description of the benefits of the product for the body.
Patients are oblivious and believe they are receiving legitimate medications.
We do hope that our government will direct more resources to these fraudulent activities and take the necessary actions to protect the public. One physician has already been charged with a felony after deceiving and administering laboratory Semaglutide to patients.
Please see the link below