Evidence map›Paper›PMID 33236115›Full record

Trial reportThe Journal of clinical endocrinology and metabolism2021

Dual GIP and GLP-1 Receptor Agonist Tirzepatide Improves Beta-cell Function and Insulin Sensitivity in Type 2 Diabetes.

Melissa K Thomas, Amir Nikooienejad, Ross Bray, Xuewei Cui, Jonathan Wilson, Kevin Duffin, Zvonko Milicevic, Axel Haupt, Deborah A Robins

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Journal of clinical endocrinology and metabolism, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 178 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
178citing papers in PubMed, 11 pooled it
18.4field-weighted citation impact, top 1% of its field
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

178 citing papers in PubMed, 11 syntheses or guidelines pooled it, 305 citations in OpenAlex.

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118 more citing papers are in PubMed but not listed here.

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

9 authors at 1 institution in 1 country.

Melissa K ThomasEli Lilly and Company, Indianapolis, IN, USA.
Amir NikooienejadEli Lilly and Company, Indianapolis, IN, USA.
Ross BrayEli Lilly and Company, Indianapolis, IN, USA.
Xuewei CuiEli Lilly and Company, Indianapolis, IN, USA.
Jonathan WilsonEli Lilly and Company, Indianapolis, IN, USA.
Kevin DuffinEli Lilly and Company, Indianapolis, IN, USA.
Zvonko MilicevicEli Lilly and Company, Vienna, Austria.
Axel HauptEli Lilly and Company, Indianapolis, IN, USA.
Deborah A RobinsEli Lilly and Company, Indianapolis, IN, USA.
Eli Lilly (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

contextNovel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist (RA) tirzepatide demonstrated substantially greater glucose control and weight loss (WL) compared with selective GLP-1RA dulaglutide.

objectiveExplore mechanisms of glucose control by tirzepatide.

designPost hoc analyses of fasting biomarkers and multiple linear regression analysis.

settingForty-seven sites in 4 countries. PATIENTS OR OTHER

participantsThree hundred and sixteen subjects with type 2 diabetes.

interventionsTirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), placebo.

main outcome measuresAnalyze biomarkers of beta-cell function and insulin resistance (IR) and evaluate WL contributions to IR improvements at 26 weeks.

resultsHomeostatic model assessment (HOMA) 2-B significantly increased with dulaglutide and tirzepatide 5, 10, and 15 mg compared with placebo (P ≤ .02). Proinsulin/insulin and proinsulin/C-peptide ratios significantly decreased with tirzepatide 10 and 15 mg compared with placebo and dulaglutide (P ≤ .007). Tirzepatide 10 and 15 mg significantly decreased fasting insulin (P ≤ .033) and tirzepatide 10 mg significantly decreased HOMA2-IR (P = .004) compared with placebo and dulaglutide. Markers of improved insulin sensitivity (IS) adiponectin, IGFBP-1, and IGFBP-2 significantly increased by 1 or more doses of tirzepatide (P < .05). To determine whether improvements in IR were directly attributable to WL, multiple linear regression analysis with potential confounding variables age, sex, metformin, triglycerides, and glycated hemoglobin A1c was conducted. WL significantly (P ≤ .028) explained only 13% and 21% of improvement in HOMA2-IR with tirzepatide 10 and 15 mg, respectively.

conclusionsTirzepatide improved markers of IS and beta-cell function to a greater extent than dulaglutide. IS effects of tirzepatide were only partly attributable to WL, suggesting dual receptor agonism confers distinct mechanisms of glycemic control.

Indexed as

Glucagon-Like Peptide-1 Receptor AgonistsInsulin ResistanceAdolescentAdultAgedBiomarkersBlood GlucoseClinical Trials, Phase II as TopicDiabetes Mellitus, Type 2FemaleFollow-Up StudiesGastric Inhibitory PolypeptideGlycated HemoglobinHumansHypoglycemic AgentsInsulin-Secreting CellsBiomarkersBlood GlucoseGastric Inhibitory PolypeptideGlucagon-Like Peptide-1 Receptor AgonistsGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsTirzepatidebeta-cell functionGIPGLP-1insulin sensitivitytirzepatidetype 2 diabetes

Identifiers

PMID33236115
PMCPMC7823251
OpenAlexW3108676144

What Socratic holds

Texttitle and abstract
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.