In brief
The paper that introduced LY3298176, later named tirzepatide, written by the company developing it. It is a fatty-acid-modified peptide that activates both the GIP and the GLP-1 receptor and is designed for once-weekly injection. In cell assays it signalled through both receptors; in mice it increased glucose-dependent insulin secretion, improved glucose tolerance and, with repeated dosing, reduced body weight and food intake. In the phase-1 programme, 142 people received at least one dose of the compound, dulaglutide or placebo; the two highest doses lowered fasting glucose in patients with type 2 diabetes relative to placebo, and four weeks of treatment reduced body weight by up to about 5 kilograms in healthy subjects and 2 to 2.6 kilograms in patients. The most frequent adverse effects were gastrointestinal, dose-dependent and rated mild to moderate.
Study design
Discovery-to-clinic paper: receptor assays, mouse studies, then a phase-1 programme with single and four-week multiple ascending doses in healthy subjects and a four-week proof-of-concept in type 2 diabetes.
What it does not show
Four-week exposure, small groups and a company-authored report. The later phase-3 trials cited alongside it are where the efficacy claims for tirzepatide actually come from.
A clinical trial tests a pharmaceutical form of a compound, in a defined patient group, under medical supervision, with a defined endpoint. None of that transfers to a research-grade vial, and this page does not suggest it does.
Where this paper is cited
- Tirzepatide — The discovery paper: a GIP-biased dual agonist with a fatty diacid for weekly dosing, and its first clinical proof of concept.
Other papers cited for Tirzepatide
- Study in humans Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial Garvey et al. (2023), Lancet
- Study in humans Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes Frías et al. (2021), N Engl J Med
Further reading
- Research library: every paper cited on this site, by compound and by study type.
- GLP-1 family comparison
- How to read a certificate of analysis
- Lyophilised peptide storage and stability
How this page was made: the citation was retrieved from PubMed by PMID and checked against the title on the product page; the summary was written from the paper's abstract and reports only what the abstract reports. Read the paper itself before relying on any figure here.