Evidence mapPaperPMID 41391569Full record

Trial reportMolecular metabolism2026

Long-acting GIPR agonist LY3537021 reduces body weight and fasting blood glucose in patients with T2D: Preclinical development and phase 1 randomized ascending dose studies.

William Roell, Jorge Alsina-Fernandez, Hongchang Qu, Tamer Coskun, Charles Benson, Axel Haupt, Ronan P Kelly, Libbey O'Farrell, Kyle W Sloop, James P Steele and 6 more

Registry-linked trialAbstract readClinical Trial, Phase IRandomized Controlled Trial
In one paragraph

Trial report in Molecular metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04586907 (A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY3537021 in Healthy Participants and Patients With Type 2 Diabetes Mellitus), which is not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT04586907 phase1completednot on this map

A Single- and Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of LY3537021 in Healthy Participants and Patients With Type 2 Diabetes Mellitus

TypeinterventionalSponsorEli Lilly and CompanyRan2020 to 2021Enrolled85ConditionsHealthy, Type 2 Diabetes MellitusArmsLY3537021, Placebo
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

William RoellEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: roell_william_c@lilly.com.
Jorge Alsina-FernandezEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: alsina-fernandez_jorge@lilly.com.
Hongchang QuEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: qu_hongchang@lilly.com.
Tamer CoskunEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: coskun_tamer@lilly.com.
Charles BensonEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: benson_charles_t@lilly.com.
Axel HauptEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: haupt_axel@lilly.com.
Ronan P KellyEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: kelly_ronan_p@lilly.com.
Libbey O'FarrellEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: ofarrell_libbey_s@lilly.com.
Kyle W SloopEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: sloop_kyle_w@lilly.com.
James P SteeleEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: steele_james_patrick@lilly.com.
James FicorilliEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: ficorilli_james@lilly.com.
Ajit RegmiEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: regmi_ajit@lilly.com.
Mallikarjuna RettigantiEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: rettiganti_mallikarjuna@lilly.com.
Shweta UrvaEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: urva_shweta@lilly.com.
Kieren J MatherEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: kieren.mather@lilly.com.
Edward PrattEli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285, USA. Electronic address: pratt_edward_john@lilly.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTirzepatide, a single-molecule dual glucose-dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor (R) agonist, has shown superiority in the reduction of blood glucose and body weight, above selective GLP-1R agonists, but the contribution of GIP to these effects remains incompletely understood.

objectivesTo characterize the preclinical and in-human effects of a long-acting GIPR agonist monotherapy in healthy participants and patients with type 2 diabetes (T2D).

methodsA long-acting GIPR agonist (LY3537021) was characterized in vitro and in Long-Evans diet-induced obese rats and Wistar rats. Next, a phase 1, randomized, placebo-controlled, single ascending dose (SAD)/multiple ascending dose (MAD) study explored the safety, tolerability, pharmacokinetics, and pharmacodynamics of LY3537021 in healthy participants and participants with T2D in Singapore.

resultsIn vitro, LY3537021 demonstrated potency greater than native GIP and selectivity for the GIPR. In vivo in rats, chronic treatment with LY3537021 resulted in weight loss and improved glycemic control during a glucose tolerance test. The phase 1 clinical study enrolled 85 healthy participants and patients with T2D (SAD, n = 47 [aged 25-64 years]; MAD, n = 38 [aged 25-69 years]; average baseline BMI was 25.9-27.0 kg/m

conclusionsIn vivo studies demonstrated that LY3537021 reduced body weight and improved glycemia during a glucose challenge in rats. The phase 1 study demonstrated that the long-acting GIPR agonist LY3537021 was well tolerated, induced weight loss, and improved glucose control in humans. These observations better define the therapeutic benefit of long-acting GIPR agonists and support a distinct contribution of GIP agonism to the benefits observed with multi-agonist peptides that act via the GIPR. Future studies are needed in more diverse populations and in cohorts with overweight/obesity to confirm these findings. CLINICALTRIALS: GOV: NCT04586907.

Indexed as

Blood GlucoseBody WeightDiabetes Mellitus, Type 2Hypoglycemic AgentsReceptors, Gastrointestinal HormoneAdultAgedAnimalsDouble-Blind MethodDrug Evaluation, PreclinicalFastingFemaleGastric Inhibitory PolypeptideHumansMaleMiddle AgedBlood GlucoseGastric Inhibitory Polypeptidegastric inhibitory polypeptide receptorHypoglycemic AgentsReceptors, Gastrointestinal HormoneTirzepatideBody weightFasting glucoseGIPR agonistPharmacodynamicsPharmacokineticsType 2 diabetes mellitus

Identifiers

PMID41391569
PMCPMC12808604

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.