Studies of Tirzepatide in Obesity and Type 2 Diabetes

by | Feb 1, 2023 | Research


Tirzepatide is a novel peptide that is a modified version of the human incretins called glucose-dependent insulinotropic polypeptide (GIP), formerly known as gastric inhibitory peptide and GLP-1 (Glucagon-like peptide-1).

The human duodenum and small intestines normally produce incretins after a meal, and an incretin’s function is to stimulate insulin production.[1] This may help the body produce enough insulin before glucose is released into the bloodstream.

Tirzepatide peptide has 14 unique amino acids (engineered from the GIP sequence) and an amidated exenatide-like (GLP-1 agonist) C terminus. It is made of 39 amino acids and has a sequence of YXEGTFTSDY SIXLDKIAQK AFVQWLIAGG PSSGAPPPS. Tirzepatide was developed to activate both the GLP-1 and GIP receptors. In general, it activates GIP more significantly than GLP-1. Furthermore, Tirzepatide peptide is also lipidated, which improves its bioavailability and stability.

Scientists are investigating its potential as a therapy for obesity, osteoporosis, and Parkinson’s, as well as treatment for type 2 diabetes.

Research on the Potential Benefits of Tirzepatide


Tirzepatide peptide and type 2 diabetes patients

Tirzepatide appears to help diabetes patients control their blood sugar levels by activating both the GIP and GLP-1 receptors. Both receptors can be found in the pancreas and other organs such as the gut, heart, and brain.[2,3] Activating the receptors in the pancreas leads to the release of insulin and improved control over blood sugar levels. Tirzepatide peptide is under active study as to its efficacy in triggering these receptors.

The effect of Tirzepatide peptide appears to be glucose-dependent, so the peptide may not trigger insulin secretion if glucose levels are low or average. Therefore, Tirzepatide may have an advantage over many other anti-diabetic medications as it is not likely to cause hypoglycemia.

Another possible advantage of the dual-agonist properties of Tirzepatide peptide is that it may lead to better glycemic control than GLP-1 agonists. A meta-analysis of 26 randomized control trials observed that Tirzepatide had higher efficacy than Semaglutide, Liraglutide, Sitagliptin, Canagliflozin, and Empagliflozin.[4] The researchers concluded that “Tirzepatide, oral and SC semaglutide has a favorable efficacy in treating T2DM.

Another meta-analysis which included more than 7000 participants, reported similar results, observing that Tirzepatide peptide experiments led to at least 5 kg of weight loss in as little as 8 weeks of therapy in the test subjects.[5]

Further studies suggest that Tirzepatide has the potential to reduce appetite and calorie intake, leading to weight loss and improved insulin sensitivity.[6] Some scientists suggest that a significant part of the improvement in insulin sensitivity may be independent of weight loss. 

For example, one study with 316 participants with type 2 diabetes reported that about 15-20% of the improvement in insulin sensitivity was weight loss related, while the other 80-85% was apparently attributed to the effects of the peptide.[7] Moreover, the researchers noted that the beneficial effects on insulin resistance and glucose control appear to be greater than other experimental peptides which appear to activate GLP-1 alone, such as Dulaglutide.

Recent studies also suggest that Tirzepatide’s effects on type 2 diabetes patients may help reduce the risk of complications such as diabetic nephropathy.


Tirzepatide & Obesity

Tirzepatide peptide may have the potential to help with weight loss regardless of whether a patient has diabetes or not. The largest study on obese non-diabetic individuals was conducted in 2022 and covered more than 2500 patients.[9] In 17 months of therapy, the participants lost a whopping 20% or more of their body weight. Considering the average weight of the patients was 104kg, they lost at least 20 kg or more of their body mass. 

Tirzepatide may also lead to a significant reduction of visceral fat. In contrast to subcutaneous fat, visceral fat is the adipose tissue that deposits around and inside the internal organs. Small amounts of visceral fats are essential for the normal functioning of the organs and the human body. However, obese individuals also often have increased levels of visceral fat. This is called visceral obesity, which can lead to severe metabolic problems. This is because visceral fat is more metabolically active than subcutaneous fat and releases significant amounts of proinflammatory cytokines and triglycerides in the bloodstream.[10] As a result, an elevated level of inflammation and triglycerides in the body leads to insulin resistance, unfavorable lipid profile, etc.

Ultimately, research suggests visceral obesity is a significant risk factor for debilitating chronic conditions such as type 2 diabetes, heart disease, and cancer.[11] Studies hypothesize that Tirzepatide may help with weight loss and visceral fat reduction. One trial in obese individuals with fatty liver reported that for 12 months of therapy, the peptide led to an average of 8% reduction in liver fat.[12] The researchers concluded that “Tirzepatide peptide showed a significant reduction in LFC and VAT and ASAT volumes compared with insulin degludec in this subpopulation of patients with type 2 diabetes in the SURPASS-3 study. ” Despite the research suggesting the significant effect of the peptide on weight loss, as of 2023, the peptide is still in testing and is not approved for the management of obesity with related comorbidities. 



Tirzepatide appears to be the first dual-agonist anti-diabetic peptide that activates both the GIP and GLP-1 receptors in the pancreas and other body parts. This may lead to more significant weight loss and glycemic control benefits than the previous from the same class.

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  1. Thorens B. (1995). Glucagon-like peptide-1 and control of insulin secretion. Diabete & metabolisme, 21(5), 311–318.
  2. Usdin, T. B., Mezey, E., Button, D. C., Brownstein, M. J., & Bonner, T. I. (1993). Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain. Endocrinology, 133(6), 2861–2870.
  3. Abu-Hamdah R, Rabiee A, Meneilly GS, Shannon RP, Andersen DK, Elahi D. Clinical review: The extrapancreatic effects of glucagon-like peptide-1 and related peptides. J Clin Endocrinol Metab. 2009 Jun;94(6):1843-52. doi: 10.1210/jc.2008-1296. Epub 2009 Mar 31. PMID: 19336511; PMCID: PMC2690432.
  4. Zaazouee, M. S., Hamdallah, A., Helmy, S. K., Hasabo, E. A., Sayed, A. K., Gbreel, M. I., Elmegeed, A. A., Aladwan, H., Elshanbary, A. A., Abdel-Aziz, W., Elshahawy, I. M., Rabie, S., Elkady, S., Ali, A. S., Ragab, K. M., & Nourelden, A. Z. (2022). Semaglutide for the treatment of type 2 Diabetes Mellitus: A systematic review and network meta-analysis of safety and efficacy outcomes. Diabetes & metabolic syndrome, 16(6), 102511.
  5. Permana, H., Yanto, T. A., & Hariyanto, T. I. (2022). Efficacy and safety of tirzepatide as novel treatment for type 2 diabetes: A systematic review and meta-analysis of randomized clinical trials. Diabetes & metabolic syndrome, 16(11), 102640.
  6. Frias JP, Nauck MA, Van J, Benson C, Bray R, Cui X, Milicevic Z, Urva S, Haupt A, Robins DA. Efficacy and tolerability of tirzepatide, a dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes: A 12-week, randomized, double-blind, placebo-controlled study to evaluate different dose-escalation regimens. Diabetes Obes Metab. 2020 Jun;22(6):938-946. doi: 10.1111/dom.13979. Epub 2020 Feb 11. PMID: 31984598; PMCID: PMC7318331.
  7. Thomas, M. K., Nikooienejad, A., Bray, R., Cui, X., Wilson, J., Duffin, K., Milicevic, Z., Haupt, A., & Robins, D. A. (2021). Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes. The Journal of clinical endocrinology and metabolism, 106(2), 388–396.
  8. 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.
  9. Heerspink HJL, Sattar N, Pavo I, Haupt A, Duffin KL, Yang Z, Wiese RJ, Tuttle KR, Cherney DZI. Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes in the SURPASS-4 trial: post-hoc analysis of an open-label, randomised, phase 3 trial. Lancet Diabetes Endocrinol. 2022 Nov;10(11):774-785. doi: 10.1016/S2213-8587(22)00243-1. Epub 2022 Sep 21. PMID: 36152639.
  10. Tchernof A, Després JP. Pathophysiology of human visceral obesity: an update. Physiol Rev. 2013 Jan;93(1):359-404. doi: 10.1152/physrev.00033.2011. PMID: 23303913.
  11. Dhawan D, Sharma S. Abdominal Obesity, Adipokines and Non-communicable Diseases. J Steroid Biochem Mol Biol. 2020 Oct;203:105737. doi: 10.1016/j.jsbmb.2020.105737. Epub 2020 Aug 18. PMID: 32818561; PMCID: PMC7431389.
  12. Gastaldelli A, Cusi K, Fernández Landó L, Bray R, Brouwers B, Rodríguez Á. Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial. Lancet Diabetes Endocrinol. 2022 Jun;10(6):393-406. doi: 10.1016/S2213-8587(22)00070-5. Epub 2022 Apr 22. PMID: 35468325.