Evidence map›Paper›PMID 43015368›Full record

ArticleNature metabolism2026

Rare GLP1R variants attenuate weight loss with semaglutide but not tirzepatide.

Matthew E Levy, Kelly M Schiabor Barrett, Natalie Telis, William H Lagarde, Pradyumna D Phatak, James F Maher, Chad Haldeman-Englert, Joseph J Grzymski, Douglas Stoller, Amy C Sturm and 11 more

Abstract read
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In one paragraph

Article in Nature metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

21 authors.

Matthew E LevyHelix, San Mateo, CA, USA. matt.levy@helix.com.ORCID http://orcid.org/0000-0002-2164-1726
Kelly M Schiabor BarrettHelix, San Mateo, CA, USA.ORCID http://orcid.org/0000-0001-6194-787X
Natalie TelisHelix, San Mateo, CA, USA.
William H LagardeDepartment of Pediatrics, WakeMed Health and Hospitals, Raleigh, NC, USA.
Pradyumna D PhatakRochester Regional Health, Rochester, NY, USA.ORCID http://orcid.org/0000-0002-9661-5004
James F MaherTriHealth Cancer Institute, Cincinnati, OH, USA.
Chad Haldeman-EnglertCone Health Precision Health, Greensboro, NC, USA.
Joseph J GrzymskiUniversity of Nevada School of Medicine, Reno, NV, USA.
Douglas StollerUniversity of Nebraska Medical Center, Omaha, NE, USA.ORCID http://orcid.org/0000-0002-4064-4324
Amy C SturmThe Ohio State University Wexner Medical Center, Columbus, OH, USA.
Daniel P JudgeDivision of Cardiology, Medical University of South Carolina, Charleston, SC, USA.ORCID http://orcid.org/0000-0002-3407-0248
C Anwar A ChahalCenter for Inherited Cardiovascular Diseases, WellSpan Health, Ephrata, PA, USA.ORCID http://orcid.org/0000-0001-7825-8827
Jamie L RenbargerParkview Health, Fort Wayne, IN, USA.
Christopher N ChapmanDepartment of Pathology & Laboratory Medicine, St. Luke's University Health Network, Bethlehem, PA, USA.
Steven F PowellSanford Health, Sioux Falls, SD, USA.
Douglas A OlsonHealthPartners, Minneapolis, MN, USA.
Kent ShefchekHelix, San Mateo, CA, USA.
Lisa M McEwenHelix, San Mateo, CA, USA.
Nicole L WashingtonHelix, San Mateo, CA, USA.ORCID http://orcid.org/0000-0001-8936-9143
William LeeHelix, San Mateo, CA, USA.
Elizabeth T CirulliHelix, San Mateo, CA, USA.ORCID http://orcid.org/0000-0001-7808-2809

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Weight loss with glucagon-like peptide-1 receptor agonists (GLP-1RAs) is heterogeneous across individuals, yet the genetic causes of this variation are not fully known. We integrated exome sequencing data with electronic health records within the Helix Research Network (n = 351,818). Here, we show that, among 13,725 GLP-1RA-treated adults, carriers of rare damaging GLP1R variants lose less weight with semaglutide than matched non-carriers but achieve a near-normal tirzepatide response. Carriers of rare variants in GIPR, which encodes the glucose-dependent insulinotropic polypeptide receptor, the second target of tirzepatide, also achieve normal weight loss responses. Our study demonstrates that rare GLP1R variants affect the response to semaglutide but not to tirzepatide.

Identifiers

PMID43015368

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Registered trials

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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 OpenQuestion graph.