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Tirzepatide

Tirzepatide is a synthetically modified analog of gastric inhibitory polypeptide (GIP) with affinity at the glucagon-like peptide-1 (GLP-1) receptor. It was recently approved in the US to help type 2 diabetes patients better manage blood sugar. Tirzepatide is under active study as a weight loss agent and for its cardioprotective and anti-inflammatory properties

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    What is Tirzepatide?

    Tirzepatide (LY3298176) is a synthetic peptide agonist of both the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. With a length of 39 amino acids, tirzepatide is primarily based on human GIP and modified with a C20 fatty di-acid moiety to extend its duration and thus allow for once-weekly subcutaneous administration [1, 2].

    What are GIP and GLP-1?

    GIP is an incretin that is secreted from K cells in the upper small intestine in response to food, and is responsible for the majority of the insulinotropic incretin effect in man. GLP-1 is also an incretin, but which also inhibits glucagon secretion in the hyperglycaemic and normoglycaemic states. The hormone slows gastric emptying, promotes satiety, and reduces food intake, and GLP-1 analogs like semaglutide have had their own success as type 2 diabetes treatments [1, 2, 3, 4].

    Research indicates that tirzepatide’s activation of both the GLP-1 and GIP receptors produces a synergistic effect to exert greater insulin and glucagonostatic responses, compared to administering GIP or GLP-1 alone. This makes the peptide a powerful tool in the treatment of both type 2 diabetes and obesity [1, 3].

    Tirzepatide Regulatory Status

    Following completion of clinical trials in type 2 diabetes patients, tirzepatide became roundly acknowledged as a potent glucose lowering and weight loss agent with a comparable safety profile to other GLP-1 receptor agonists [5, 6, 7, 8, 9].

    In May 2022, the US Food and Drug Administration approved tirzepatide as an adjunct treatment of type 2 diabetes, available by prescription under brand name Mounjaro [10].

    Licensed researchers may also buy tirzepatide online as a reference material for laboratory experimentation only.

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    Tirzepatide Benefits | Clinical Trials

    Tirzepatide has already been demonstrated as an effective treatment of type 2 diabetes, and is additionally being investigated as an obesity treatment and for its cardioprotective effect.

    While a number of clinical trials involving tirzepatide are pending through at least 2024, here is a summary of the published results to date.

    Tirzepatide as a Weight Loss Agent

    Through its activation of GIP receptors in fat cells, tirzepatide works to decrease adipose inflammation while increasing adiponectin, thus reducing fat cell differentiation and increasing energy expenditure, leading to weight loss [11].

    In late 2022, Eli Lilly commenced SURMOUNT, a development program comprising four global phase 3 trials to assess the efficacy and safety of tirzepatide as an adjunct treatment of chronic weight management in adults with a BMI of 27 or greater [12].

    Numbering over 2,500 participants, the first trial confirmed the efficacy of tirzepatide in inducing weight loss in the obese and overweight patients, with average weight reductions of tirzepatide 16% on 5mg/weekly, 21.4% on tirzepatide 10mg/weekly, and 22.5% on tirzepatide 15 mg/weekly, administered for a duration of 72 weeks. Results for the remaining trials are expected to be published in 2023 [12, 13].

    Tirzepatide as a Type 2 Diabetes Treatment

    As mentioned, animal research has shown that tirzepatide regulates hypothalamic feeding centers via GIP signaling, resulting in improved glucose handling and reduced food intake [11].

    Tirzepatide has demonstrated superiority to diabetes treatments like dulaglutide and semaglutide in terms of glycemic control and obesity reduction. In one study, researchers found that tirzepatide was more effective than semaglutide at reducing hemoglobin A1c and inducing weight loss in type 2 diabetes patients [6, 14].

    Based on its superior effectiveness compared to these other diabetes therapies in clinical studies, tirzepatide was approved by the US Food and Drug Administration as an adjunct treatment to improve blood sugar control in adults with type 2 diabetes [10].

    Tirzepatide and Cardioprotection

    Through its selective targeting of GLP-1 receptors, tirzepatide plays a role in abating inflammation, a condition that contributes to the initiation and progression of atherosclerosis [4]. Tirzepatide also increases adiponectin, and researchers have found a correlation between high levels of adiponectin and a reduced risk of coronary heart disease [15].

    In a 26-week study on patients with type 2 diabetes, researchers found that once-weekly tirzepatide injections improved lipoprotein biomarkers associated with insulin resistance and cardiovascular risk while lowering triglycerides, suggesting a net lowering of the patients’ risk of of heart disease [16].

    A pending cardiovascular outcomes study is expected to provide a clearer picture on the cardiovascular benefit of tirzepatide, compared to treatment with the GLP-1 receptor agonist dulaglutide [17]. Learn more about the benefits of Tirzepatide here.

    Tirzepatide Side Effects

    Clinical trial data indicates that tirzepatide is generally well tolerated and is not associated with serious adverse effects in obese patients with or without type 2 diabetes [5, 6, 7, 8, 9, 13].

    There are minor side effects linked with tirzepatide administration, and these generally subside with discontinuation of treatment or an adjustment of the total weekly tirzepatide dose.

    Tirzepatide may induce the following side effects, most of which are GI tract related [5, 6, 7, 8, 9, 13]:

    • Nausea
    • Diarrhea
    • Vomiting
    • Decreased appetite
    • Indigestion
    • Constipation
    • Abdominal pain
    • Dyspepsia
    • Hypersensitivity reactions

    Due to its gastric emptying effect and lack of data in patients with severe gastrointestinal disease, researchers are advised against administering tirzepatide to subjects with serious gastroparesis [18].

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    Is Tirzepatide Safe?

    Based on extensive clinical study (the SURPASS program), the US Food and Drug Administration has deemed tirzepatide safe for use in adults with type 2 diabetes [5, 6, 7, 8, 9, 10].

    For example, in the phase 3 SURPASS-1 trial, the investigators deemed that tirzepatide had a safety profile consistent with that of other GLP-1 receptor agonists, while in the phase 3 SURPASS-4 trial, the investigators ruled out excess cardiovascular risk as a safety concern in administering tirzepatide to type 2 diabetes patients [5, 6].

    While safety studies for other indications are still pending, studies into using tirzepatide as a treatment of obesity in adults (the SURMOUNT program), have already yielded positive outcomes [12, 13].

    As a research chemical, tirzepatide is intended to be handled strictly by professional researchers and their authorized assistants, bearing in mind that the peptide has only been approved for use as a type 2 diabetes treatment to date.

    To see information on the safe and effective administration of tirzepatide, researchers may refer to the Mounjaro (tirzepatide) package insert published by Eli Lilly. Here are some noteworthy points regarding the safe administration of tirzepatide [18]:

    • Administer tirzepatide via subcutaneous injection (i.e. into the fatty tissue beneath the subject’s skin, typically in the abdomen, thigh, or upper arm). Researchers are advised to rotate the site of injection with each weekly administration.
    • Tirzepatide is contraindicated in subjects with any history of medullary thyroid carcinoma, as the peptide has been found to cause thyroid C-cell tumors in rats. It is further contraindicated in subjects with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
    • Administering tirzepatide concomitantly with insulin or an insulin secretagogue may result in a higher risk of hypoglycemia.
    • Tirzepatide may slow absorption of certain oral medications. Researchers should also closely monitor subjects who are being administered drugs with a narrow therapeutic index.

    Tirzepatide Dosage Calculator

    There are no set guidelines for dosing tirzepatide in a research setting, as the peptide may be studied for a range of applications.

    On the other hand, reference may be made to the dosing schedules followed in both the Mounjaro (tirzepatide) package insert and clinical trials involving the peptide [5, 6, 7, 8, 9, 13, 18].

    Based on the aforecited sources, researchers may refer to the following tirzepatide dosing protocol for weight loss in obese subjects:

    • Tirzepatide Dose: Starting dose of 2.5mg/week for the first four weeks of the study period, thereafter increased to a total weekly dose of 5mg, with subsequent increases of the total weekly dose in 2.5/mg increments, as needed.
    • Frequency: Administer once weekly as a subcutaneous injection.
    • Study Duration: 12-24 weeks.
    • Notes: Both the Mounjaro package insert document and clinical trials have adopted a maximum tirzepatide dose of 15mg/week.

    Where To Buy Tirzepatide Online

    Tirzepatide is available by prescription to patients who have a medical need for treatment. The drug is not sold online to individuals for therapeutic purposes.

    On the other hand, qualified researchers and laboratory professionals may legally buy tirzepatide online for in vitro testing.

    Researchers are advised to avoid purchasing tirzepatide from online peptide vendors who do not clearly state that their peptides are intended for research purposes only, or similar.

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    FAQ

    How to Reconstitute Tirzepatide

    Tirzepatide that is provided in lyophilized (freeze-dried) powder form must be reconstituted with bacteriostatic water prior to injection. To reconstitute tirzepatide, extract the correct amount of bacteriostatic water from its vial and insert into the tirzepatide vial, letting the water slowly enter before swirling the solution until dissolved.

    How is Tirzepatide Delivered?

    Tirzepatide is intended to be delivered via subcutaneous injection, into the fatty tissue beneath the subject’s skin, typically in the abdomen.

    How to Take Tirzepatide

    Tirzepatide should be administered once weekly at a dose ranging from 2.5mg to 15mg, depending on the study phase, research objective, and test subject.

    Tirzepatide For Sale | Verdict

    Tirzepatide is a novel, FDA-approved medication that acts on both the GIP and GLP-1 receptors to improve insulin sensitivity, induce weight loss, and favorably impact the lipid profiles of type 2 diabetes patients.

    It is now targeted as an obesity treatment, with positive data from the SURMOUNT clinical trial program already published and further results pending.

    The overall safety data and relative lack of adverse effects further support the use of this dual GIP/GLP-1 receptor agonist in a range of clinical applications.

    Licensed researchers who wish to buy tirzepatide online for investigation should head over to Peptide Sciences, a trusted name in the research peptides industry.

    References

    1. Coskun T, Sloop KW, Loghin C, Alsina-Fernandez J, Urva S, Bokvist KB, Cui X, Briere DA, Cabrera O, Roell WC, Kuchibhotla U, Moyers JS, Benson CT, Gimeno RE, D'Alessio DA, Haupt A. LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept. Mol Metab. 2018 Dec;18:3-14. doi: 10.1016/j.molmet.2018.09.009. Epub 2018 Oct 3. PMID: 30473097; PMCID: PMC6308032.
    2. Thomas MK, Nikooienejad A, Bray R, et al. Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. J Clin Endocrinol Metab. 2021;106(2):388-396. doi:10.1210/clinem/dgaa863
    3. Min T, Bain SC. The Role of Tirzepatide, Dual GIP and GLP-1 Receptor Agonist, in the Management of Type 2 Diabetes: The SURPASS Clinical Trials. Diabetes Ther. 2021;12(1):143-157. doi:10.1007/s13300-020-00981-0
    4. Tate M, Chong A, Robinson E, Green BD, Grieve DJ. Selective targeting of glucagon-like peptide-1 signalling as a novel therapeutic approach for cardiovascular disease in diabetes. Br J Pharmacol. 2015;172(3):721-736. doi:10.1111/bph.12943
    5. Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, Mao H, Cui X, Karanikas CA, Thieu VT. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021 Jul 10;398(10295):143-155. doi: 10.1016/S0140-6736(21)01324-6. Epub 2021 Jun 27. Erratum in: Lancet. 2021 Jul 17;398(10296):212. PMID: 34186022.
    6. Frías JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25. PMID: 34170647.
    7. Ludvik, B., Giorgino, F., Jódar, E., Frias, J. P., Landó, L. F., Brown, K., Bray, R., & Rodríguez, Á. (2021, August 6). Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (surpass-3): A randomised, open-label, parallel-group, phase 3 trial. The Lancet. Retrieved August 9, 2022, from https://www.sciencedirect.com/science/article/abs/pii/S0140673621014434
    8. Prato, S. D., Kahn, S. E., Pavo, I., Weerakkody, G. J., Yang, Z., Doupis, J., Aizenberg, D., Wynne, A. G., Riesmeyer, J. S., Heine, R. J., & Wiese, R. J. (2021, October 18). Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (surpass-4): A randomised, open-label, parallel-group, multicentre, phase 3 trial. The Lancet. Retrieved August 9, 2022, from https://www.sciencedirect.com/science/article/abs/pii/S0140673621021887
    9. Dahl D, Onishi Y, Norwood P, Huh R, Bray R, Patel H, Rodríguez Á. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 2022 Feb 8;327(6):534-545. doi: 10.1001/jama.2022.0078. PMID: 35133415; PMCID: PMC8826179.
    10. FDA Approves Novel, Dual-Targeted Treatment for Type 2 Diabetes". U.S. Food and Drug Administration (FDA) (Press release)
    11. Zhang, Qian et al. “The glucose-dependent insulinotropic polypeptide (GIP) regulates body weight and food intake via CNS-GIPR signaling.” Cell metabolism vol. 33,4 (2021): 833-844.e5. doi:10.1016/j.cmet.2021.01.015
    12. le Roux CW, Zhang S, Aronne LJ, Kushner RF, Chao AM, Machineni S, Dunn J, Chigutsa FB, Ahmad NN, Bunck MC. Tirzepatide for the treatment of obesity: Rationale and design of the SURMOUNT clinical development program. Obesity (Silver Spring). 2023 Jan;31(1):96-110. doi: 10.1002/oby.23612. Epub 2022 Dec 7. PMID: 36478180.
    13. Jastreboff AM, Aronne LJ, Ahmad NN, Wharton S, Connery L, Alves B, Kiyosue A, Zhang S, Liu B, Bunck MC, Stefanski A; SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022 Jul 21;387(3):205-216. doi: 10.1056/NEJMoa2206038. Epub 2022 Jun 4. PMID: 35658024.
    14. Vadher, Karan et al. “Efficacy of tirzepatide 5, 10 and 15 mg versus semaglutide 2 mg in patients with type 2 diabetes: An adjusted indirect treatment comparison.” Diabetes, obesity & metabolism, 10.1111/dom.14775. 19 May. 2022, doi:10.1111/dom.14775
    15. Yanai H, Yoshida H. Beneficial Effects of Adiponectin on Glucose and Lipid Metabolism and Atherosclerotic Progression: Mechanisms and Perspectives. International Journal of Molecular Sciences. 2019; 20(5):1190. https://doi.org/10.3390/ijms20051190
    16. Wilson, JM, Nikooienejad, A, Robins, DA, et al. The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes. Diabetes Obes Metab. 2020; 22: 2451– 2459.
    17. National Library of Medicine (U.S.). (2020, May 29 - ). A Study of Tirzepatide (LY3298176) Compared With Dulaglutide on Major Cardiovascular Events in Participants With Type 2 Diabetes (SURPASS-CVOT). Identifier NCT04255433. https://www.clinicaltrials.gov/ct2/show/NCT04255433
    18. Highlights of prescribing information ... - eli lilly and company. (n.d.). Retrieved January 10, 2023, from https://pi.lilly.com/us/mounjaro-uspi.pdf?s=pi

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