# References — The Tirzepatide Source Cabinet

> Primary-source references underpinning the Get Tirzepatide cabinet: SURPASS, SURMOUNT, SUMMIT, SURMOUNT-OSA, SYNERGY-NASH, SURMOUNT-5, pharmacokinetic studies, and the structural pharmacology record.

## Cabinet VII — The Source Record

**The Folios, Fully Cited.** Eighteen primary sources from the published clinical and pharmacological record on tirzepatide. Every figure on every page in the cabinet is traceable to one of these folios.

## About this folio list

Every quantitative claim on the Get Tirzepatide cabinet is cited inline by a bracketed number that resolves to one of the folios below. The list is ordered by first appearance in the cabinet, not by author or year. Where possible, links resolve to PubMed, PubMed Central, or the journal's primary record; the digital object identifier (DOI) is provided for every entry. Readers who wish to read the original record are encouraged to follow the links and read the trial protocols and methods sections in full — the cabinet abridges; the folios do not.

## Primary sources

[01] Rosenstock J, et al. 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. The Lancet. 2021. DOI: 10.1016/S0140-6736(21)01324-6. PubMed: https://pubmed.ncbi.nlm.nih.gov/34186022/

[02] Frias JP, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine. 2021. DOI: 10.1056/NEJMoa2107519. Article: https://www.nejm.org/doi/full/10.1056/NEJMoa2107519

[03] Jastreboff AM, et al. Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. 2022. DOI: 10.1056/NEJMoa2206038. Article: https://www.nejm.org/doi/full/10.1056/NEJMoa2206038

[04] Willard FS, et al. Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist. JCI Insight. 2020. DOI: 10.1172/jci.insight.140532. PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7526454/

[05] Schneck KB, et al. Population pharmacokinetics of the GIP/GLP receptor agonist tirzepatide. CPT: Pharmacometrics & Systems Pharmacology. 2024. DOI: 10.1002/psp4.13099. PubMed: https://pubmed.ncbi.nlm.nih.gov/38356317/

[06] Packer M, et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity (SUMMIT). New England Journal of Medicine. 2024. DOI: 10.1056/NEJMoa2410027. Article: https://www.nejm.org/doi/abs/10.1056/NEJMoa2410027

[07] Malhotra A, et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity (SURMOUNT-OSA). New England Journal of Medicine. 2024. DOI: 10.1056/NEJMoa2404881. Article: https://www.nejm.org/doi/abs/10.1056/NEJMoa2404881

[08] Loomba R, et al. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis (SYNERGY-NASH). New England Journal of Medicine. 2024. DOI: 10.1056/NEJMoa2401943. Article: https://www.nejm.org/doi/abs/10.1056/NEJMoa2401943

[09] Aronne LJ, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5). New England Journal of Medicine. 2025. DOI: 10.1056/NEJMoa2416394. Article: https://www.nejm.org/doi/full/10.1056/NEJMoa2416394

[10] Heerspink HJL, et al. 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. The Lancet Diabetes & Endocrinology. 2022. DOI: 10.1016/S2213-8587(22)00243-1. Article: https://www.thelancet.com/journals/landia/article/PIIS2213-8587(22)00243-1/abstract

[11] de Boer IH, et al. Systolic blood pressure reduction with tirzepatide in patients with type 2 diabetes: insights from the SURPASS clinical program. Cardiovascular Diabetology. 2023. DOI: 10.1186/s12933-023-01775-x. PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039543/

[12] Del Prato S, et al. 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. 2021. DOI: 10.1016/S0140-6736(21)02188-7. Article: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02188-7/abstract

[13] Sun B, et al. Structural determinants of dual incretin receptor agonism by tirzepatide. Proceedings of the National Academy of Sciences. 2022. DOI: 10.1073/pnas.2116506119. PMC: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9060465/

[14] Tirzepatide, a dual GIP/GLP-1 receptor agonist, alleviates metabolic dysfunction-associated steatotic liver disease by reducing the expression of CD36 and OBP2A. Biochemical and Biophysical Research Communications. 2025. DOI: 10.1016/j.bbrc.2025.151849. PubMed: https://pubmed.ncbi.nlm.nih.gov/40837406/

[15] Hankosky ER, et al. Tirzepatide and the 10-year predicted risk of cardiovascular disease and type 2 diabetes in adults with obesity and prediabetes: A post hoc analysis from the three-year SURMOUNT-1 trial. Diabetes, Obesity and Metabolism. 2025. DOI: 10.1111/dom.70143. Article: https://dom-pubs.onlinelibrary.wiley.com/doi/full/10.1111/dom.70143

[16] Wang Y, et al. Dual GLP-1 and GIP Agonist Tirzepatide Exerted Neuroprotective Action in a Parkinson's Disease Rat Model. Journal of Molecular Neuroscience. 2025. DOI: 10.1007/s12031-025-02312-z. PubMed: https://pubmed.ncbi.nlm.nih.gov/39964252/

[17] Farzam K, Patel P. Tirzepatide. StatPearls, NCBI Bookshelf. 2024. ID: NBK585056. URL: https://www.ncbi.nlm.nih.gov/books/NBK585056/

[18] Heerspink HJL, et al. Tirzepatide Associated With Reduced Albuminuria in Participants With Type 2 Diabetes: Pooled Post Hoc Analysis From the Randomized Active- and Placebo-Controlled SURPASS-1-5 Clinical Trials. Diabetes Care. 2025. DOI: 10.2337/dc24-1773. Article: https://diabetesjournals.org/care/article/48/3/430/157650/

## A note on what is not cited here

Phase-four observational studies, registry analyses, and post-marketing pharmacovigilance reports are not cited above. The cabinet is built on the published phase-three trial programme, the structural and pharmacokinetic literature, and a small number of preclinical mechanism papers — that is, the primary clinical-evidence base. Real-world-evidence literature on tirzepatide is sizeable and growing; readers interested in that record are encouraged to consult the relevant systematic reviews and meta-analyses, which the cabinet treats as derivative of the trial sources cited above.

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