Evidence mapPaperPMID 38211595Full record

Trial reportDiabetes care2024

Longitudinal Effects of Glucose-Lowering Medications on β-Cell Responses and Insulin Sensitivity in Type 2 Diabetes: The GRADE Randomized Clinical Trial.

Neda Rasouli, Naji Younes, Alokananda Ghosh, Jeanine Albu, Robert M Cohen, Ralph A DeFronzo, Elsa Diaz, Laure Sayyed Kassem, José A Luchsinger, Janet B McGill 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 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

17 citing papers in PubMed, 15 citations in OpenAlex.

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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 10 institutions in 1 country.

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
Naji YounesThe Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Alokananda GhoshThe Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Jeanine AlbuIcahn School of Medicine, Mount Sinai Morningside, New York, NY.
Robert M CohenDivision of Endocrinology, Diabetes and Metabolism, University of Cincinnati College of Medicine and Cincinnati VA Medical Center, Cincinnati, OH.
Ralph A DeFronzoUniversity of Texas Health Science Center, San Antonio, TX.ORCID 0000-0002-8581-6273
Elsa DiazVA San Diego Healthcare System, San Diego, CA.
Laure Sayyed KassemDepartment of Endocrinology, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, OH.
José A LuchsingerDepartments of Medicine and Epidemiology, Columbia University Irving Medical Center, New York, NY.ORCID 0000-0002-5886-3648
Janet B McGillDivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO.
William I SivitzDepartment of Internal Medicine, University of Iowa, Iowa City, IA.ORCID 0000-0002-7829-0189
William V TamborlaneYale School of Medicine, New Haven, CT.ORCID 0000-0002-9928-559X
Kristina M UtzschneiderDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle.ORCID 0000-0002-4924-196X
Steven E KahnDivision of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle.ORCID 0000-0001-7307-9002
GRADE Research Group
Milken Institute · USUniversity of Washington · USVA San Diego Healthcare System · USCincinnati VA Medical Center · USColumbia University Irving Medical Center · USLouis Stokes Cleveland VA Medical Center · USThe University of Texas Health Science Center at San Antonio · USUniversity of Iowa · USVA Eastern Colorado Health Care System · USWashington University in St. Louis · 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
Yale Clinical and Translational Science AwardUL1TR001863 · YALE UNIVERSITY · 2025 to 2025
$9.9M
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
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 TR001863NCATS 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 TR004528NIDDK 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 P30 DK111022NIDDK NIH HHS U01 DK098246NIDDK NIH HHS U01DK098246NIDDK NIH HHS U34 DK088043NIGMS NIH HHS U54 GM104940
6 · The paper itself

Abstract

objectiveTo compare the long-term effects of glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, and sitagliptin) when added to metformin on insulin sensitivity and β-cell function. RESEARCH DESIGN AND

methodsIn the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) cohort with type 2 diabetes (n = 4,801), HOMA2 was used to estimate insulin sensitivity (HOMA2-%S) and fasting β-cell function (HOMA2-%B) at baseline and 1, 3, and 5 years on treatment. Oral glucose tolerance test β-cell responses (C-peptide index [CPI] and total C-peptide response [incremental C-peptide/incremental glucose over 120 min]) were evaluated at the same time points. These responses adjusted for HOMA2-%S in regression analysis provided estimates of β-cell function.

resultsHOMA2-%S increased from baseline to year 1 with glargine and remained stable thereafter, while it did not change from baseline in the other treatment groups. HOMA2-%B and C-peptide responses were increased to variable degrees at year 1 in all groups but then declined progressively over time. At year 5, CPI was similar between liraglutide and sitagliptin, and higher for both than for glargine and glimepiride [0.80, 0.87, 0.74, and 0.64 (nmol/L)/(mg/dL) * 100, respectively; P < 0.001], while the total C-peptide response was greatest with liraglutide, followed in descending order by sitagliptin, glargine, and glimepiride [1.54, 1.25, 1.02, and 0.87 (nmol/L)/(mg/dL) * 100, respectively, P < 0.001]. After adjustment for HOMA2-%S to obtain an estimate of β-cell function, the nature of the change in β-cell responses reflected those in β-cell function.

conclusionsThe differential long-term effects on insulin sensitivity and β-cell function of four different glucose-lowering medications when added to metformin highlight the importance of the loss of β-cell function in the progression of type 2 diabetes.

Indexed as

Diabetes Mellitus, Type 2Insulin ResistanceMetforminSulfonylurea CompoundsBlood GlucoseC-PeptideGlucoseHumansHypoglycemic AgentsInsulin GlargineLiraglutideSitagliptin PhosphateBlood GlucoseC-PeptideglimepirideGlucoseHypoglycemic AgentsInsulin GlargineLiraglutideMetforminSitagliptin PhosphateSulfonylurea Compounds

Identifiers

PMID38211595
PMCPMC10973918
OpenAlexW4390766400

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.