Trial reportDiabetes care2025

Weight Gain Was Associated With Worsening Glycemia and Cardiovascular and Kidney Outcomes in Patients With Type 2 Diabetes Independent of Diabetes Medication in the GRADE Randomized Controlled Trial.

Deborah J Wexler, W Timothy Garvey, Alokananda Ghosh, Erin J Kazemi, Heidi Krause-Steinrauf, Andrew J Ahmann, Janet Brown-Friday, Sabina Casula, Andrea L Cherrington, Tom A Elasy and 6 more

Registry-linked trialAbstract readRandomized Controlled Trial
In one paragraph

Trial report in Diabetes care, 2025. The graph read 4 numbers from its abstract, feeding 4 cells of the map: it . It reports registered trial NCT01794143. Cited by 5 papers.

4numbers the graph read from it
4cells of the map it votes in
5citing 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.

← favours the treatmentfavours the comparator →
-3.801.200 · no effect
Weight change (kg) during the first yearliraglutidefavours the treatment · ascvd, t2dfeeds one cell of the map
Δ -3.50-3.80 to -3.20< 0.0001
Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide,-1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride (P < 0.0001).
Weight change (kg) during the first yearglarginefavours the comparator · ascvd, t2dfeeds one cell of the map
Δ 0.450.16 to 0.74< 0.0001
Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide,-1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride (P < 0.0001).
Weight change (kg) during the first yearglimepiridefavours the comparator · ascvd, t2dfeeds one cell of the map
Δ 0.890.60 to 1.20< 0.0001
Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide,-1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride (P < 0.0001).
Weight change (kg) during the first yearsitagliptinfavours the treatment · ascvd, t2dfeeds one cell of the map
Δ -1.07-1.40 to -0.78< 0.0001
Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide,-1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride (P < 0.0001).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

DPP-4 inhibitors×body weight & composition

No readable resultOpen on the map →What to test next →

29 readable studies in this cell: 8 favour the treatment, 8 find no difference, 13 favour the comparator.

Belief with this paper
0.50contested · 4 families support, 4 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2025
Δ -1.07-1.40 to -0.78
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT011066771,284 enrolled · 2010
Δ -2.40-3.00 to -1.80
NCT007344741,202 enrolled · 2008
Δ -1.70-2.27 to -1.14
NCT007010901,035 enrolled · 2008
Δ -2.00-2.30 to -1.60
NCT00575588891 enrolled · 2007
Δ -2.20-2.70 to -1.70
NCT00676338820 enrolled · 2008
Δ -1.28-1.92 to -0.63
NCT00432276803 enrolled · 2007
Δ -0.50-1.03 to 0.04
NCT01137812756 enrolled · 2010
Δ -2.80-3.30 to -2.20
NCT01682759751 enrolled · 2012
IRR -3.70-10.6 to 3.30
NCT01438814689 enrolled · 2011
Δ 0.620.25 to 0.98
NCT02849080504 enrolled · 2016
Δ -1.90-2.60 to -1.20
NCT00642278451 enrolled · 2008
Δ 0.40-0.50 to 1.40

GLP-1 receptor agonists×body weight & composition

No readable resultOpen on the map →What to test next →

40 readable studies in this cell: 83 favour the treatment, 15 find no difference, 11 favour the comparator.

Belief with this paper
0.90replicated · 64 families support, 7 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2025
Δ -3.50-3.80 to -3.20
NCT012722193,731 enrolled · 2011
Δ -5.39-5.82 to -4.95
Δ -17.3-18.1 to -16.6
NCT017204463,297 enrolled · 2013
Δ -2.95-3.47 to -2.44
NCT035489351,961 enrolled · 2018
Δ -12.4-13.4 to -11.5
NCT039879191,879 enrolled · 2019
Δ -1.70-2.60 to -0.70
NCT026078651,864 enrolled · 2016
Δ -2.50-3.00 to -2.00
NCT056467061,407 enrolled · 2023
Δ -14.8-16.2 to -13.4
NCT018365231,398 enrolled · 2013
Δ -4.90-5.65 to -4.16
NCT035527571,210 enrolled · 2018
Δ -6.21-7.28 to -5.15
NCT007344741,202 enrolled · 2008
Δ -1.50-2.08 to -0.92
Δ -10.4-11.2 to -9.50
NCT020581471,170 enrolled · 2014
Δ 14.38.37 to 20.3

Insulin×body weight & composition

No readable resultOpen on the map →What to test next →

12 readable studies in this cell: 1 favour the treatment, 1 find no difference, 10 favour the comparator.

Belief with this paper
0.00contested · 0 families support, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2025
Δ 0.450.16 to 0.74
NCT037306622,002 enrolled · 2018
Δ -9.00-9.80 to -8.30
NCT038829701,444 enrolled · 2019
Δ -9.80-10.8 to -8.80
NCT045379231,428 enrolled · 2020
Δ -10.7-11.5 to -9.90
NCT020581471,170 enrolled · 2014
Δ 40.633.6 to 47.6
NCT04093752917 enrolled · 2019
Δ -6.50-7.40 to -5.60
NCT01768559894 enrolled · 2013
Δ -1.99-2.59 to -1.40
NCT01075282810 enrolled · 2010
Δ 2.832.33 to 3.33
NCT02551874650 enrolled · 2015
Δ -3.64-4.20 to -3.09

Sulfonylureas & glinides×body weight & composition

No readable resultOpen on the map →What to test next →

15 readable studies in this cell: 2 favour the treatment, 1 find no difference, 12 favour the comparator.

Belief with this paper
0.27contested · 1 family supports, 2 contradict · against placebo
Without itNot a counted family in this claim, so removing it changes nothing.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2025
Δ 0.890.60 to 1.20
NCT009688121,452 enrolled · 2009
Δ -5.20-5.70 to -4.70
NCT006609071,217 enrolled · 2008
Δ -4.65-5.14 to -4.17
NCT003184611,091 enrolled · 2006
Δ -3.75-4.48 to -3.01
NCT03332771954 enrolled · 2017
Δ -3.58-4.65 to -2.52
NCT02471404939 enrolled · 2015
Δ -5.30-5.93 to -4.67
NCT00575588891 enrolled · 2007
Δ -2.20-2.70 to -1.70
NCT01682759751 enrolled · 2012
IRR -3.70-10.6 to 3.30
NCT00294723746 enrolled · 2006
Δ -3.58-4.28 to -2.87
NCT02033889621 enrolled · 2013
Δ -1.60-2.16 to -1.03
NCT02419612444 enrolled · 2015
Δ -4.06-4.84 to -3.28
NCT00393718400 enrolled · 2006
Least Squares Mean -1.91-2.34 to -1.48
NCT02564926125 enrolled · 2016
Δ -2.60-3.35 to -1.82
4 · 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
5 · Its place in the literature

Who cites it

5 citing papers in PubMed.

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

Corrections and comments

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

7 · Who and what money

Authors and funding

16 authors.

Deborah J WexlerDiabetes Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA.ORCID 0000-0001-6979-402X
W Timothy GarveyDepartment of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL.ORCID 0000-0003-0822-0860
Alokananda GhoshThe Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Erin J KazemiThe Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.
Heidi Krause-SteinraufThe Biostatistics Center, Department of Biostatistics and Bioinformatics, Milken Institute School of Public Health, The George Washington University, Rockville, MD.ORCID 0000-0001-6894-4110
Andrew J AhmannDivision of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health and Science University, Portland, OR.ORCID 0000-0002-4544-5404
Janet Brown-FridayDepartment of Medicine, Albert Einstein College of Medicine, Bronx, NY.
Sabina CasulaEndocrinology, Diabetes, and Metabolism, Bruce W. Carter Department of Veterans Affairs Medical Center, Miami, FL.
Andrea L CherringtonDivisions of Preventive and General Internal Medicine, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL.ORCID 0000-0002-8321-3567
Tom A ElasyVanderbilt University Medical Center, Nashville, TN.
Stephen P FortmannKaiser Permanente Center for Health Research, Portland, OR.
Jonathan A KrakoffObesity and Diabetes Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Sunder MudaliarVeterans Affairs San Diego Healthcare System and Division of Endocrinology and Metabolism, University of California, San Diego School of Medicine, La Jolla, CA.
Margaret TiktinLouis Stokes Cleveland Veterans Affairs Medical Center and Case Western Reserve University, Cleveland, OH.
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
GRADE Study Research Group

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
North Carolina Translational and Clinical Sciences Institute (NC TraCS)UM1TR004406 · UNIV OF NORTH CAROLINA CHAPEL HILL · 2025 to 2025
$8.6M
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
UAB Nutrition Obesity Research Center (NORC)P30DK056336 · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2000 to 2025
$6.0M
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
American Diabetes AssociationCDC HHSNCATS NIH HHS UL1 TR000170NCATS NIH HHS UL1 TR000439NCATS NIH HHS UL1 TR000445NCATS NIH HHS UL1 TR001102NCATS 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 TR002541NCATS NIH HHS UL1 TR002548NCATS NIH HHS UM1 TR004406NCATS NIH HHS UM1 TR004528NHLBI NIH HHSNIDDK NIH HHS P30 DK017047NIDDK NIH HHS P30 DK020541NIDDK NIH HHS P30 DK020572NIDDK NIH HHS P30 DK056336NIDDK NIH HHS P30 DK072476NIDDK NIH HHS P30 DK079626NIDDK NIH HHS P30 DK092926NIDDK NIH HHS U01 DK098246NIDDK NIH HHS U01DK098246NIDDK NIH HHS U34 DK088043NIDDK NIH HHS U34-DK-088043NIGMS NIH HHS U54 GM104940
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

objectiveWeight gain with glucose-lowering medications may interfere with effective type 2 diabetes (T2D) management. We evaluated weight change and the effect of weight gain on outcomes over 5 years on four diabetes medications. RESEARCH DESIGN AND

methodsThe Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) randomized trial compared the addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin in participants with T2D. We report weight change and hazard ratio (HR) per kilogram of weight change for HbA1c >7.5%; cardiovascular disease (CVD), kidney disease, and neuropathy outcomes; and diabetes treatment satisfaction.

resultsParticipants (n = 4,980) were 57 ± 10 years, 44% non-White, with HbA1c 7.5% ± 0.5%, and BMI 34.3 ± 6.8 kg/m2. Mean (95% CI) weight change (kg) during the first year was -3.5 (-3.8,-3.2) with liraglutide,-1.07 (-1.4,-0.78) with sitagliptin, 0.45 (0.16, 0.74) with glargine, and 0.89 (0.60, 1.2) with glimepiride (P < 0.0001). Thereafter, weight decreased in all groups. Weight gain within the first 6 months was associated with increased risk of HbA1c >7.5%, with modest differences by treatment, and with subsequent CVD (HR 1.03 [95% CI 1.005, 1.06]). Weight gain at 1 year was associated with increased risk of HbA1c >7.5% (HR 1.05 [1.04, 1.07]) and kidney disease (HR 1.03 [1.01, 1.06]). Baseline weight, but not weight gain, was associated with new-onset neuropathy. Weight gain was associated with lower diabetes treatment satisfaction.

conclusionsLiraglutide and sitagliptin were associated with initial weight loss and glargine and glimepiride with slight weight gain, followed by weight loss in metformin-treated T2D. Weight gain was associated with worsening glycemia and increased risk of cardiovascular and kidney outcomes largely independent of treatment.

Indexed as

Cardiovascular DiseasesDiabetes Mellitus, Type 2Hypoglycemic AgentsWeight GainAgedBlood GlucoseFemaleGlycated HemoglobinHumansInsulin GlargineLiraglutideMaleMetforminMiddle AgedSitagliptin PhosphateSulfonylurea CompoundsBlood GlucoseglimepirideGlycated HemoglobinHypoglycemic AgentsInsulin GlargineLiraglutideMetforminSitagliptin PhosphateSulfonylurea Compounds

Identifiers

PMID40267365
PMCPMC12094209

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.