FOR RESEARCH USE ONLY. NOT FOR HUMAN OR VETERINARY USE. NOT FOR HUMAN CONSUMPTION.
Compounds described on this site are supplied solely for laboratory research. They are not offered for human or veterinary use or for clinical use, and they are not intended to diagnose, mitigate, cure or prevent any disease.
Tirzepatide is a synthetic peptide reported as an agonist at both the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the GLP-1 receptor. Four publications are reviewed: three laboratory studies of receptor pharmacology and structure, and SURMOUNT-1, a 72-week randomised, double-blind, placebo-controlled phase 3 trial whose results are kept separate for each study arm. The U.S. FDA has approved a drug product containing tirzepatide; PepGenex research material is not that product, and the trial figures apply only to the material that trial used.
At a glance
Also identified as
LY3298176
Class
Dual hormone receptor agonist (GIPR, GLP-1R)
Target or mechanism
Agonist — GIP receptor; GLP-1 receptor
Evidence types represented
in vitro, human
Published studies reviewed
4
Regulatory and registry records
1
Last reviewed
2026-09-24
U.S. FDA status
An FDA approved drug product containing tirzepatide exists. Source: Drugs@FDA, Applications NDA 215866 and NDA 217806.
Overview
Tirzepatide is a synthetic peptide reported to act as an agonist at two receptors: the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R).
The study recorded on this page is SURMOUNT-1: a double-blind, randomised, placebo-controlled trial over 72 weeks in adults with obesity, or with overweight and at least one coexisting condition, and without diabetes, published in the New England Journal of Medicine in 2022.
Its results are reported separately for each of three tirzepatide arms, and they are recorded that way here. A single headline number for this trial is a number that has had the amounts averaged out of it, and the difference between the arms is large enough that the average describes none of them.
Regulatory status
An FDA approved drug product containing tirzepatide exists. PepGenex research materials are not that product, are not FDA approved, and are not for human or veterinary use.
Source: Drugs@FDA, Applications NDA 215866 and NDA 217806. Verified 2026-09-24.
Mechanism under investigation
Tirzepatide
Agonist
→
GIP receptor
GLP-1 receptor
Described in the literature as an agonist at both the GIP and the GLP-1 receptor. The trial recorded on this page measured endpoints, not mechanism.
Scope of the published work
Areas investigated
Body weight
Cardiometabolic measures
Tolerability
Models used
Randomised human study
Every figure on this page was recorded in a controlled trial, under supervision, using material prepared for that trial, in a population selected by its entry criteria. It is not the research material PepGenex supplies and no result here transfers to it.
Limitations
Evidence represented on this page: in vitro and human. No animal research is represented. The page reviews 4 published studies, and each figure is reported for the study that published it; results are not pooled across studies.
Common questions
What is Tirzepatide?
Tirzepatide is a synthetic peptide reported to act as an agonist at two receptors: the glucose-dependent insulinotropic polypeptide receptor (GIPR) and the glucagon-like peptide-1 receptor (GLP-1R).
How does Tirzepatide work, according to the published research?
Described in the literature as an agonist at both the GIP and the GLP-1 receptor. The trial recorded on this page measured endpoints, not mechanism.
Cryo-electron microscopy structures of tirzepatide bound to the human GIP receptor (3.1 Å) and the human GLP-1 receptor (2.9 Å) were reported. As with the native ligands, tirzepatide adopted an α-helical conformation with its N terminus reaching deep into the transmembrane core of both receptors, and its N-terminal tyrosine (Tyr1) showed a weak interaction with the GLP-1 receptor. (Sun et al., 2022, PMID 35333651)
In a β-galactosidase enzyme fragment complementation assay of β-arrestin2 recruitment, tirzepatide showed full agonism, close to equipotent with GIP, at the GIP receptor, but a partial agonist profile reaching less than 10% Emax at the GLP-1 receptor; independent techniques gave an equivalent profile for β-arrestin1 and β-arrestin2 recruitment at both the human and mouse GLP-1 receptor. The authors describe this as signalling bias at the GLP-1 receptor favouring cAMP generation over β-arrestin recruitment. (Willard et al., 2020, PMID 32730231)
In binding assays with HEK293 cells expressing the human receptors, run without albumin, LY3298176 bound the GIP receptor with Ki = 0.135 nM (SEM 0.020) and the GLP-1 receptor with Ki = 4.23 nM (SEM 0.23). The authors reported GIP receptor affinity comparable to native GIP and GLP-1 receptor affinity approximately 5-fold weaker than native GLP-1. (Coskun et al., 2018, PMID 30473097)
What has published research on Tirzepatide found, and what are its limits?
This page records 4 publications, reporting laboratory (in vitro) work in 3, human work in 1. Each is listed with its identifier under References.
Human studies represented: Jastreboff et al., 2022, PMID 35658024.
Evidence represented on this page: in vitro and human.
No animal research is represented.
The page reviews 4 published studies, and each figure is reported for the study that published it; results are not pooled across studies.
Every figure on this page was recorded in a controlled trial, under supervision, using material prepared for that trial, in a population selected by its entry criteria. It is not the research material PepGenex supplies and no result here transfers to it.
Is Tirzepatide approved by the U.S. FDA?
An FDA approved drug product containing tirzepatide exists. PepGenex research materials are not that product, are not FDA approved, and are not for human or veterinary use.
Source: Drugs@FDA, Applications NDA 215866 and NDA 217806. Verified 2026-09-24.
What risks have published studies of Tirzepatide reported?
1 published human study on this page reports adverse events or safety measurements. Each is listed with its publication in the adverse-events section of this page.
Trial events do not establish a complete safety profile.
What adverse events have been reported in published studies of Tirzepatide?
Adverse events and safety measurements as reported by the published human studies on this page. Each entry is attributed to its publication.
Jastreboff et al., 2022, PMID 35658024
Design and population
Double-blind, randomised, placebo-controlled trial over 72 weeks in adults with obesity, or with overweight and at least one weight-related coexisting condition, and without diabetes. Participants were assigned to one of three tirzepatide arms or to placebo.
Events reported
The most common adverse events in the tirzepatide arms were gastrointestinal. Most were mild to moderate in severity and occurred primarily while the amount given was being increased.
Trial events do not establish a complete safety profile.
Published research
Grouped by the kind of study. Select one to narrow what is shown below.
Laboratory (in vitro)(3)
Laboratory (in vitro)
Structural determinants of dual incretin receptor agonism by tirzepatide
Sun B, Willard FS, Feng D, et al., Proceedings of the National Academy of Sciences of the United States of America, 2022;119(13):e2116506119
published
Cryo-electron microscopy structures of tirzepatide bound to the human GIP receptor (3.1 Å) and the human GLP-1 receptor (2.9 Å) were reported. As with the native ligands, tirzepatide adopted an α-helical conformation with its N terminus reaching deep into the transmembrane core of both receptors, and its N-terminal tyrosine (Tyr1) showed a weak interaction with the GLP-1 receptor.
Molecular dynamics simulations indicated a greater propensity for intermittent hydrogen bonding between the lipid moiety of tirzepatide and the GIP receptor than the GLP-1 receptor, consistent with a more compact tirzepatide–GIP receptor complex. The authors report that at the GIP receptor tirzepatide tolerates its fatty acid modification with an affinity equalling that of GIP.
Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist
Willard FS, Douros JD, Gabe MB, et al., JCI Insight, 2020;5(17):e140532
published
In a β-galactosidase enzyme fragment complementation assay of β-arrestin2 recruitment, tirzepatide showed full agonism, close to equipotent with GIP, at the GIP receptor, but a partial agonist profile reaching less than 10% Emax at the GLP-1 receptor; independent techniques gave an equivalent profile for β-arrestin1 and β-arrestin2 recruitment at both the human and mouse GLP-1 receptor. The authors describe this as signalling bias at the GLP-1 receptor favouring cAMP generation over β-arrestin recruitment.
In internalisation assays with SNAP-tagged receptors, tirzepatide and GIP produced comparable internalisation of the GIP receptor, whereas tirzepatide was less effective than GLP-1 at internalising the GLP-1 receptor (<40% Emax). The finding was corroborated by on-cell Western assays and confocal imaging in HEK293 cells expressing epitope- and EGFP-tagged receptors.
LY3298176 (tirzepatide) was described as a 39-amino-acid linear peptide conjugated to a C20 fatty diacid moiety via a linker attached to the lysine residue at position 20. Its sequence contains two non-coded residues, α-aminoisobutyric acid (Aib), at positions 2 and 13, and its C-terminus is amidated. The reported molecular formula was C225H348N48O68, with a molecular mass of 4810.52 Da.
In binding assays with HEK293 cells expressing the human receptors, run without albumin, LY3298176 bound the GIP receptor with Ki = 0.135 nM (SEM 0.020) and the GLP-1 receptor with Ki = 4.23 nM (SEM 0.23). The authors reported GIP receptor affinity comparable to native GIP and GLP-1 receptor affinity approximately 5-fold weaker than native GLP-1.
In HEK293 cells recombinantly expressing the human GIP or GLP-1 receptor, LY3298176 stimulated cAMP accumulation with EC50 = 0.0224 nM (SEM 0.0053) at the GIP receptor and EC50 = 0.934 nM (SEM 0.068) at the GLP-1 receptor — reported as similar in potency to native GIP and approximately 13-fold weaker than GLP-1 — with minimal activity at the glucagon receptor.
Jastreboff et al., 2022 (title withheld on this site; see the publication record)
Jastreboff AM, Aronne LJ, Ahmad NN, et al.; SURMOUNT-1 Investigators, The New England Journal of Medicine, 2022;387(3):205-216
published
Double-blind, randomised, placebo-controlled trial over 72 weeks in adults with obesity, or with overweight and at least one weight-related coexisting condition, and without diabetes. Participants were assigned to one of three tirzepatide arms or to placebo.
Body weight, mean percent change from baseline (primary endpoint)
Randomised, controlled · Week 72 · Adults with obesity, or overweight with at least one coexisting condition, without diabetes
Arm
Reported
Tirzepatide (lowest dose)
-15.0% (95% CI -15.9 to -14.2)
Tirzepatide (middle dose)
-19.5% (95% CI -20.4 to -18.5)
Tirzepatide (highest dose)
-20.9% (95% CI -21.8 to -19.9)
Placebo
-3.1% (95% CI -4.3 to -1.9)
Proportion reaching a reduction in body weight of 5% or more
Randomised, controlled · Week 72 · Adults with obesity, or overweight with at least one coexisting condition, without diabetes
Arm
Reported
Tirzepatide (lowest dose)
85% (95% CI 82 to 89)
Tirzepatide (middle dose)
89% (95% CI 86 to 92)
Tirzepatide (highest dose)
91% (95% CI 88 to 94)
Placebo
35% (95% CI 30 to 39)
Proportion reaching a reduction in body weight of 20% or more
Randomised, controlled · Week 72 · Adults with obesity, or overweight with at least one coexisting condition, without diabetes
Arm
Reported
Tirzepatide (middle dose)
50% (95% CI 46 to 54)
Tirzepatide (highest dose)
57% (95% CI 53 to 61)
Placebo
3% (95% CI 1 to 5)
Proportion who stopped taking part because of adverse events
Randomised, controlled · Week 72 · Adults with obesity, or overweight with at least one coexisting condition, without diabetes
Arm
Reported
Tirzepatide (lowest dose)
4.3%
Tirzepatide (middle dose)
7.1%
Tirzepatide (highest dose)
6.2%
Placebo
2.6%
The most common adverse events in the tirzepatide arms were gastrointestinal. Most were mild to moderate in severity and occurred primarily while the amount given was being increased.
The publication reports improvements in all prespecified cardiometabolic measures in the tirzepatide arms. It does not give those measures as single figures in its abstract, and none is reproduced here.
What this study establishes
Each of the three amounts separated from placebo on the primary endpoint at week 72, and the separation grew with the amount given. The responder tables are the more informative view: they show what proportion of each arm reached a 5% and a 20% reduction, which is the distribution an average figure hides.
Limitations
Three arms is not one result, and the figures are printed separately because the lowest- and highest-dose arms differ by nearly six percentage points. Alongside them sits the rate at which people stopped taking part because of adverse events — between 4.3% and 7.1% across the tirzepatide arms, against 2.6% on placebo — which belongs to the same trial and the same 72 weeks.
Classification, structure, recorded targets, evidence types and FDA status only, each read from the two compounds' own pages. These comparisons do not compare study results.
An FDA approved drug product containing tirzepatide exists. Source: Drugs@FDA, Applications NDA 215866 and NDA 217806.
Not shown (no Drugs@FDA application record verified for this page)
References
Published studies reviewed (4)
Jastreboff et al., 2022 (title withheld on this site; see the publication record) — Jastreboff AM, Aronne LJ, Ahmad NN, et al.; SURMOUNT-1 Investigators, The New England Journal of Medicine, 2022;387(3):205-216
DOI 10.1056/NEJMoa2206038 · PMID 35658024 · NCT04184622
Coskun et al., 2018 (title withheld on this site; see the publication record) — Coskun T, Sloop KW, Loghin C, et al., Molecular Metabolism, 2018;18:3-14
DOI 10.1016/j.molmet.2018.09.009 · PMID 30473097 · PMC6308032
Structural determinants of dual incretin receptor agonism by tirzepatide — Sun B, Willard FS, Feng D, et al., Proceedings of the National Academy of Sciences of the United States of America, 2022;119(13):e2116506119
DOI 10.1073/pnas.2116506119 · PMID 35333651 · PMC9060465
