Evidence mapPaperPMID 38190619Full record

Trial reportDiabetes care2024

Impact of Insulin Sensitivity and β-Cell Function Over Time on Glycemic Outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE): Differential Treatment Effects of Dual Therapy.

Kristina M Utzschneider, Naji Younes, Nicole M Butera, Ashok Balasubramanyam, Richard M Bergenstal, Joshua Barzilay, Cyrus DeSouza, Ralph A DeFronzo, Tom Elasy, Jonathan Krakoff and 5 more

Registry-linked trialOpen access · bronzeAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It reports registered trial NCT01794143. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
2.5field-weighted citation impact, top 10% 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.

NCT01794143 phase3completed

Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study

Ran2013Enrolled7,850Registered outcomes4Posted comparisons0ConditionsComparative Effectiveness of Glycemia-lowering Medications, Type 2 DiabetesArmsDPP-4 inhibitor (sitagliptin), GLP-1 receptor agonist (liraglutide), Insulin (glargine), Sulfonylurea (glimepiride)
Open the trial in the graph
3 · Its place in the literature

Who cites it

4 citing papers in PubMed, 7 citations in OpenAlex.

  1. Trial
  2. Review
  3. Exploring the potential role of C-peptide in type 2 diabetes management.Diabetic medicine : a journal of the British Diabetic Association · 2025
    Review
  4. 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

15 authors at 13 institutions in 1 country.

Kristina M UtzschneiderVA Puget Sound Health Care System and Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA.ORCID 0000-0002-4924-196X
Naji YounesThe Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.ORCID 0000-0002-8913-0340
Nicole M ButeraThe Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Ashok BalasubramanyamDivision of Diabetes, Endocrinology and Metabolism, Baylor College of Medicine, Houston, TX.ORCID 0000-0003-2093-5201
Richard M BergenstalInternational Diabetes Center, HealthPartners Institute, Minneapolis, MN.ORCID 0000-0002-9050-5584
Joshua BarzilayDepartment of Endocrinology, Kaiser Permanente of Georgia, Duluth, GA.ORCID 0000-0001-7044-4166
Cyrus DeSouzaDivision of Diabetes, Endocrinology and Metabolism, University of Nebraska and Omaha VA Medical Center, Omaha, NE.ORCID 0000-0001-6660-0568
Ralph A DeFronzoDiabetes Division, University of Texas Health Science Center at San Antonio, San Antonio, TX.ORCID 0000-0002-8581-6273
Tom ElasyVanderbilt University Medical Center, Nashville, TN.
Jonathan KrakoffDivision of General Internal Medicine and Public Health, Southwestern American Indian Center, Phoenix, AZ.
Steven E KahnVA Puget Sound Health Care System and Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA.ORCID 0000-0001-7307-9002
Neda RasouliDivision of Endocrinology, Metabolism and Diabetes, Department of Medicine, University of Colorado School of Medicine, and VA Eastern Colorado Health Care System, Aurora, CO.ORCID 0000-0003-1269-3580
Willy M ValenciaGeriatric Research Education and Clinical Center, Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL.
William I SivitzDepartment of Internal Medicine, Endocrinology and Metabolism, University of Iowa, Iowa City, IA.ORCID 0000-0002-7829-0189
GRADE Research Group
University of Iowa · USCleveland Clinic · USAmerican Indian Center · USVA Eastern Colorado Health Care System · USUniversity of Washington · USKaiser Permanente · USThe University of Texas Health Science Center at San Antonio · USHealthPartners · USMilken Institute · USBaylor College of Medicine · USOmaha VA Medical Center · USVanderbilt University Medical Center · USUniversity of Miami · US

Funding

Continuation of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) StudyU01DK098246 · NIDDK · GEORGE WASHINGTON UNIVERSITY · PI Heidi Krause-Steinrauf, JOHN M LACHIN · 2021 to 2022
$21.0M
Vector and Transgenic Mouse CoreP30DK017047 · NIDDK · UNIVERSITY OF WASHINGTON · 1986 to 2025
$12.6M
Vanderbilt Institute for Clinical and Translational Research (VICTR)UL1TR002243 · VANDERBILT UNIVERSITY MEDICAL CENTER · 2025 to 2025
$10.7M
Washington University Institute of Clinical and Translational SciencesUL1TR002345 · WASHINGTON UNIVERSITY · 2025 to 2025
$9.3M
Georgia Clinical & Translational Science Alliance (Georgia CTSA)UL1TR002378 · EMORY UNIVERSITY · 2025 to 2025
$9.3M
Clinical and Translational Science Collaborative of Northern Ohio, Catalyzing Linkages for Everyone's Health (CLE Health)UM1TR004528 · CASE WESTERN RESERVE UNIVERSITY · 2025 to 2025
$7.9M
Pilot and Feasibility ProgramP30DK020572 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 to 2025
$4.9M
Louisiana Clinical and Translational Science CenterU54GM104940 · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2025 to 2025
$3.9M
NYR-Diabetes Research Center (NYR-DRC)P30DK020541 · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2025 to 2025
$2.4M
Pilot and Feasibility ProgramP30DK072476 · LSU PENNINGTON BIOMEDICAL RESEARCH CTR · 2005 to 2025
$2.2M
UAB Diabetes Research CenterP30DK079626 · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2025 to 2025
$1.3M
Pilot and Feasibility ProgramP30DK092926 · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2025 to 2025
$779k
CDC HHSNCATS NIH HHS UL1 TR000439NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001108NCATS NIH HHS UL1 TR001409NCATS NIH HHS UL1 TR001425NCATS NIH HHS UL1 TR001449NCATS NIH HHS UL1 TR002243NCATS NIH HHS UL1 TR002345NCATS NIH HHS UL1 TR002378NCATS NIH HHS UL1 TR002489NCATS NIH HHS UL1 TR002529NCATS NIH HHS UL1 TR002535NCATS NIH HHS UL1 TR002537NCATS NIH HHS UL1 TR002548NCATS NIH HHS UM1 TR004528NHLBI NIH HHSNIDDK NIH HHS P30 DK017047NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK072476NIDDK NIH HHS P30 DK079626NIDDK NIH HHS P30 DK092926NIDDK NIH HHS U01 DK098246NIDDK NIH HHS U01DK098246NIDDK NIH HHS U34 DK088043NIGMS NIH HHS U54 GM104940
6 · The paper itself

Abstract

objectiveTo compare the effects of insulin sensitivity and β-cell function over time on HbA1c and durability of glycemic control in response to dual therapy. RESEARCH DESIGN AND

methodsGRADE participants were randomized to glimepiride (n = 1,254), liraglutide (n = 1,262), or sitagliptin (n = 1,268) added to baseline metformin and followed for mean ± SD 5.0 ± 1.3 years, with HbA1c assessed quarterly and oral glucose tolerance tests at baseline, 1, 3, and 5 years. We related time-varying insulin sensitivity (HOMA 2 of insulin sensitivity [HOMA2-%S]) and early (0-30 min) and total (0-120 min) C-peptide (CP) responses to changes in HbA1c and glycemic failure (primary outcome HbA1c ≥7% [53 mmol/mol] and secondary outcome HbA1c >7.5% [58 mmol/mol]) and examined differential treatment responses.

resultsHigher HOMA2-%S was associated with greater initial HbA1c lowering (3 months) but not subsequent HbA1c rise. Greater CP responses were associated with a greater initial treatment response and slower subsequent HbA1c rise. Higher HOMA2-%S and CP responses were each associated with lower risk of primary and secondary outcomes. These associations differed by treatment. In the sitagliptin group, HOMA2-%S and CP responses had greater impact on initial HbA1c reduction (test of heterogeneity, P = 0.009 HOMA2-%S, P = 0.018 early CP, P = 0.001 total CP) and risk of primary outcome (P = 0.005 HOMA2-%S, P = 0.11 early CP, P = 0.025 total CP) but lesser impact on HbA1c rise (P = 0.175 HOMA2-%S, P = 0.006 early CP, P < 0.001 total CP) in comparisons with the glimepiride and liraglutide groups. There were no differential treatment effects on secondary outcome.

conclusionsInsulin sensitivity and β-cell function affected treatment outcomes irrespective of drug assignment, with greater impact in the sitagliptin group on initial (short-term) HbA1c response in comparison with the glimepiride and liraglutide groups.

Indexed as

Diabetes Mellitus, Type 2Insulin ResistanceMetforminSulfonylurea CompoundsBlood GlucoseDrug Therapy, CombinationGlycated HemoglobinHumansHypoglycemic AgentsLiraglutideSitagliptin PhosphateTreatment OutcomeBlood GlucoseglimepirideGlycated HemoglobinHypoglycemic AgentsLiraglutideMetforminSitagliptin PhosphateSulfonylurea Compounds

Identifiers

PMID38190619
PMCPMC10973903
OpenAlexW4390660981

What Socratic holds

Texttitle and abstract
Read underepoch 390

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.