Semaglutide & Tirzepatide Exhibit Both Weight Loss and Neuroprotective Benefits.

The Remarkable Neuroprotective Benefits of Larazotide, Semaglutide (GLP-1) and Tirzepetide (GLP-1/GIP).

GLP-1 is an incretin hormone produced by intestinal L cells that have growth- factor-like and neuroprotective effects.[1,2,5] These 36 amino acid gut peptides, also known as Larazotide and Semaglutide operate through neural and hormonal pathways to regulate satiety, gut motility, and pancreatic islet function.[1,2,4,5] The pancreatic islet controls blood glucose levels that the Central Nervous System (CNS) relies on as its primary metabolic fuel.[3] Dysfunction in the pancreatic islet function causes Type 2 diabetes (T2DM) which is well known to be a factor for progressive neurodegenerative conditions such as Alzheimer’s disease (AD), Parkinson’s disease (PD), and others.[1] Current clinical trials testing GLP-1 receptor (GLP-1R) agonists demonstrate improvement in PD, AD, and diabetic patients.[1,2,3,7] The glucose-dependent insulinotropic polypeptide (GIP) is known as the GLP-1 “sister.” GIP analogs, better known as Tirzepeptide, have recently demonstrated neuroprotective effects on illness, improving the GLP-1 efficacy.[1] According to recent research, overcoming insulin resistance in the brain decreases illness progress in AD, making these peptides reliable for analysis.[1,5] The GLP-1R is present in most brain regions like the hippocampus, neocortex, hypothalamus, and cerebellum, implying that GLP-1 plays a critical signaling role.[2] GLP-1 analogs also have anti-inflammatory properties essential for combating the neurodegenerative effects of chronic inflammation, which are well known to cause disease progression.[4]

GLP-1 Agonist Benefits and Neuroprotection: 

One of the most remarkable GLP-1 functions lies in its role as a potent glucagon inhibitor in the periods following a meal, which is essential for maintaining the correct levels of glucose in the blood.[7] On the other hand, GIP enables glucagon release during fasting.[7] Since both have a crucial role in regulating glucose homeostasis, analogs have been well studied to develop treatments for T2DM and PD.[1,7] Furthermore, researchers have found that GLP-1 receptor agonists like the exendin-4 showed promising effects in their phase II clinical trial in PD patients.[2] Exendin-4 can decrease dopaminergic neurodegeneration and brain inflammation by inhibiting the recruitment and activation of glial cells in animal models.[2] Exendin-4 also has a beneficial impact on motor function and exhibited a shielding effect on CNS from illnesses.[3,4,7] These findings cause the development of GLP-1/GIP dual receptor agonists and PEGylated versions of exendin-4.[2] GLP-1/GIP dual receptor agonists have been demonstrated to cross the blood-brain barrier easily and significantly reduce the chronic inflammation response.[2,8]

GLP-1R key points.[1,2]

• The β-cell GLP-1R obtains signals from both GLP-1 and glucagon to control glucose-stimulated insulin secretion.

• Brain-derived GLP-1 is synthesized in the brainstem and generally distributed to numerous GLP-1Rs throughout the CNS.

GLP-1/GIP dual receptor agonists benefits.[1,2,4,5,6,8]

• Cross BBB easily

• Reduce chronic inflammation response

• Decrease dopaminergic neurodegeneration

• Present in most CNS regions

• Anti-inflammatory properties

• Improving motor behavior in animal models

• Decrease of alpha-synuclein (α-syn) levels

• Weight loss

• Lipid-lowering

References

1. Hölscher, C. (2022). Protective properties of GLP‐1 and associated peptide hormones in neurodegenerative disorders. British Journal of Pharmacology, 179(4), 695-714.

2. Lv, M., Xue, G., Cheng, H., Meng, P., Lian, X., Hölscher, C., & Li, D. (2021). The GLP‐1/GIP dual‐receptor agonist DA5‐CH inhibits the NF‐κB inflammatory pathway in the MPTP mouse model of Parkinson’s disease more effectively than the GLP‐1 single‐receptor agonist NLY01. Brain and Behavior, 11(8), e2231.

3. McLean, B. A., Wong, C. K., Campbell, J. E., Hodson, D. J., Trapp, S., & Drucker, D. J. (2021). Revisiting the complexity of GLP-1 action from sites of synthesis to receptor activation. Endocrine reviews, 42(2), 101-132.

4. Nauck, M. A., Quast, D. R., Wefers, J., & Meier, J. J. (2021). GLP-1 receptor agonists in the treatment of type 2 diabetes–state-of-the-art. Molecular metabolism, 46, 101102.

5. Nguyen, T. T., Ta, Q. T. H., Nguyen, T. T. D., Le, T. T., & Vo, V. G. (2020). Role of insulin resistance in the Alzheimer’s disease progression. Neurochemical research, 45(7), 1481-1491.

6. Samms, R. J., Coghlan, M. P., & Sloop, K. W. (2020). How may GIP enhance the therapeutic efficacy of GLP-1?. Trends in Endocrinology & Metabolism, 31(6), 410-421.

7. Vaccari, C., Grotto, D., Pereira, T. D. V., de Camargo, J. L. V., & Lopes, L. C. (2021). GLP-1 and GIP receptor agonists in the treatment of Parkinson’s disease: Translational systematic review and meta-analysis protocol of clinical and preclinical studies. PloS one, 16(8), e0255726.

8. Wang, Y., Cai, F., Li, G., & Tao, Y. (2022). Novel dual glucagon-like peptide- 1/glucose-dependent insulinotropic polypeptide receptor agonist attenuates diabetes and myocardial injury through inhibiting hyperglycemia, inflammation, and oxidative stress in rodent animals. Bioengineered, 13(4), 9184-9196.

Product available for research use only: