TIRZEPATIDE (GLP-2) 30mg

Tirzepatide (GLP-2) — Research Overview

Introduction

Tirzepatide is a long-acting synthetic polypeptide designed as a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP‐1) receptors. By engaging both incretin receptors, tirzepatide has been studied for effects on glycemic control, body-weight reduction, and cardiometabolic risk markers in controlled research settings. Dose-escalated once‐weekly administration is used in many protocols, with outcomes characterized across the SURPASS (type 2 diabetes) and SURMOUNT (obesity without diabetes) trial programs [1–6].

Chemical Characteristics

CAS #: 2023788-19-2
Molecular Formula: C₂₂₅H₃₄₈N₄₈O₆₈
Molecular Weight: 4813.527 g/mol

Other Known Titles: LY3298176; dual GIP/GLP‐1RA

Research Applications

1. Glycemic Control in Type 2 Diabetes (SURPASS Program)

– Tirzepatide improved HbA1c versus placebo and active comparators including semaglutide 1 mg and basal insulin in multicenter trials [1–4].

– Across studies, a high proportion of subjects reached HbA1c <7% and even normoglycemia thresholds (≤5.7%) at higher doses under intensive titration [1–3].

2. Body‐Weight Outcomes

– In participants with type 2 diabetes, tirzepatide produced clinically meaningful weight loss compared with basal insulin and semaglutide 1 mg [1–4].

– In adults with obesity without diabetes (SURMOUNT‐1), mean weight reduction approached 15–22% at the highest doses over 72 weeks, with greater proportions achieving ≥20% loss versus placebo [5].

3. Cardiometabolic Risk Markers

– Trials report favorable changes in fasting lipids (triglycerides, total/LDL cholesterol), systolic blood pressure, and inflammatory markers aligned with weight loss and glycemic improvement [1–5].

– A dedicated cardiovascular outcomes study is/was planned to assess major adverse cardiovascular events (MACE) versus an active GLP‐1 comparator [4].

4. Gastric Emptying and Appetite

– As with GLP‐1 agonism, tirzepatide delays gastric emptying acutely; tachyphylaxis to this effect has been described with chronic dosing while appetite suppression persists [1,5,6].

5. Dosing, PK/PD, and Administration

– Long effective half-life supports once‐weekly administration with gradual dose escalation to improve GI tolerability; exposure–response relationships are consistent with incretin class effects [1–4].

6. Safety/Tolerability Under Research Conditions

– The most commonly observed events are GI related (nausea, diarrhea, vomiting), generally during dose escalation. Hypoglycemia risk is low when not combined with insulin/secretagogues, but increases when co-administered; protocols include monitoring and dose adjustments [1–4].

Conclusion

Tirzepatide is a dual GIP/GLP‐1 receptor agonist studied across type 2 diabetes and obesity research programs, showing robust glycemic efficacy and substantial body‐weight reductions, with cardiometabolic marker improvements and a safety profile consistent with incretin‐based therapies. Availability and use are limited to controlled laboratory research.

Tirzepatide — References

• Frias, J. P., Davies, M. J., Rosenstock, J., Pérez Manghi, F. C., Fernández Landó, L., Bergman, B. K., Liu, B., Cui, X., & Brown, K. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine. 2021;385(6):503–515.https://doi.org/10.1056/NEJMoa2107519
• Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., Stefanski, A., & Lau, D. C. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022;387(3):205–216.https://doi.org/10.1056/NEJMoa2206038
• Min, T., Bain, S. C. The role of tirzepatide, dual GIP and GLP-1 receptor agonist, in the management of type 2 diabetes: the SURPASS clinical trials. Diabetes Therapy. 2021;12(6):1431–1445.https://doi.org/10.1007/s13300-021-01055-1
• Coskun, T., Sloop, K. W., Loghin, C., Alsina-Fernandez, J., Urva, S., Bokvist, K. B., Cui, X., Briere, D. A., Cabrera, O., Roell, W. C., Kuchibhotla, U., Demarest, K. T., & Gedulin, B. R. 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. Molecular Metabolism. 2018;18:3–14.https://doi.org/10.1016/j.molmet.2018.09.009
• Heise, T., Seewaldt-Becker, E., Macha, S., Hantel, S., Pinnetti, S., Chen, S., & Woerle, H. J. Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple ascending doses of tirzepatide in patients with type 2 diabetes: a randomised, double-blind, placebo-controlled, phase 1 study. Diabetes, Obesity and Metabolism. 2021;23(1):193–203.https://doi.org/10.1111/dom.14175
• Rosenstock, J., Wysham, C., Frías, J. P., Kaneko, S., Lee, C. J., Chiang, Y., Rodriguez, A., Milicevic, Z., & Haupt, A. Efficacy and Safety of Tirzepatide Once Weekly Versus Dulaglutide Once Weekly as Add-on Therapy to Metformin in Patients With Type 2 Diabetes (SURPASS-HEAD-TO-HEAD): A Double-Blind, Randomized, Phase 3 Trial. Diabetes Care. 2022;45(6):1250–1259.https://doi.org/10.2337/dc21-2248
• Del Prato, S., Kahn, S. E., Pavo, I., Weerakkody, G. J., Jacob, S., Doupis, J., Urva, S., Andersen, K. R., & Nauck, M. A. Tirzepatide versus Insulin Glargine in Type 2 Diabetes and Increased Cardiovascular Risk. New England Journal of Medicine. 2021;385(17):1529–1541.https://doi.org/10.1056/NEJMoa2107519
• Sattar, N., McGuire, D. K. Tirzepatide, obesity, and cardiovascular risk: Additional insights from SURMOUNT-1. The Lancet Diabetes & Endocrinology. 2022;10(9):600–602.https://doi.org/10.1016/S2213-8587(22)00205-1

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