GRADE
Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study
Sponsor study identifier
Secondary identifiers
interventional
7,850
1 country
36
Study Start
May 2013
Date type not reportedThis date has not been verified as actual or estimated.
Primary Completion
April 30, 2021
Actual (reported)Study Completion
April 30, 2021
Actual (reported)The GRADE Study is a pragmatic, unmasked clinical trial that will compare commonly used diabetes medications, when combined with metformin, on glycemia-lowering effectiveness and patient-centered outcomes.
Registry-reported information. Elapsed time and enrollment totals alone do not measure study progress or recruitment pace.
April 30, 2021
Actual (reported)Click on a node to explore related trials.
Some registry-reported names shown below are not yet linked in this graph.
Dates and qualifiers reported by the registry. Estimated dates do not confirm that a milestone has occurred.
February 13, 2013
Actual (reported)February 18, 2013
Actual (reported)May 2013
Date type not reportedThis date has not been verified as actual or estimated.
April 30, 2021
Actual (reported)April 30, 2021
Actual (reported)February 10, 2026
Actual (reported)Time to HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication
The primary metabolic outcome is the time to primary failure defined as an HbA1c\>=7% (53mmol/mol), subsequently confirmed, after addition of randomly assigned glucose-lowering medication at baseline.
Quarterly for 4 to 7 years
HbA1c>=7%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication
Number of participants who reached primary failure defined as an HbA1c\>=7% (53mmol/mol), subsequently confirmed, after addition of randomly assigned glucose-lowering medication at baseline.
Quarterly, 4-7 years
Time to HbA1c>7.5%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication.
Quarterly, 4-6 years
HbA1c>7.5%, While Receiving Metformin and the Randomly Assigned Glucose-lowering Study Medication.
Quarterly for 4 to 7 years
Sulfonylurea
DPP-4 inhibitor (sitagliptin)
GLP-1 receptor agonist (liraglutide)
Used in accordance with labeling and/or usual practice.
Used in accordance with labeling and/or usual practice
University of Alabama-Birmingham
Birmingham, Alabama, United States
Southwestern American Indian Center
Phoenix, Arizona, United States
Veterans Medical Research Foundation, San Diego (San Diego VA)
San Diego, California, United States
University of Colorado
Denver, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
South Florida VA Foundation (Miami VA)
Miami, Florida, United States
Atlanta VA Medical Center
Decatur, Georgia, United States
Butera NM, Zeng D, Heiss G, Cai J. Modeling longitudinal change in biomarkers using data from a complex survey sampling design: An application to the Hispanic Community Health Study/Study of Latinos. Stat Med. 2023 Feb 28;42(5):632-655. doi: 10.1002/sim.9635. Epub 2023 Jan 11.
Butera NM, Zeng D, Green Howard A, Gordon-Larsen P, Cai J. A doubly robust method to handle missing multilevel outcome data with application to the China Health and Nutrition Survey. Stat Med. 2022 Feb 20;41(4):769-785. doi: 10.1002/sim.9260. Epub 2021 Nov 16.
David M Nathan, MD
Massachusetts General Hospital
7,850 participants (actual enrollment reported by the registry).
First Submitted
February 13, 2013
First Posted
February 18, 2013
Study Start
May 2013
Date type not reportedThis date has not been verified as actual or estimated.
Insulin (glargine), Lantus
Used in accordance with labeling and/or usual practice.
Used in accordance with labeling and/or usual practice.
Registry-reported names are shown in full. Names without a link have not yet been matched to a Syfrah profile.
Contact the study team to confirm eligibility.
Kaiser Permanente of Georgia
Duluth, Georgia, United States
Pacific Health Research and Education Institute (VA Pacific Islands)
Honolulu, Hawaii, United States
Indiana University School of Medicine
Indianapolis, Indiana, United States
University of Iowa
Iowa City, Iowa, United States
Pennington Biomedical Research Center
Baton Rouge, Louisiana, United States
MedStar Health Research Institute
Hyattsville, Maryland, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
University of Michigan
Ann Arbor, Michigan, United States
International Diabetes Center
Minneapolis, Minnesota, United States
University of Minnesota
Minneapolis, Minnesota, United States
Washington University School of Medicine
St Louis, Missouri, United States
University of Nebraska
Omaha, Nebraska, United States
University of New Mexico School of Medicine
Albuquerque, New Mexico, United States
State University of New York (SUNY)-Downstate Medical Center
Brooklyn, New York, United States
Columbia University Naomi Berrie Diabetes Center
New York, New York, United States
Mount Sinai St. Luke's Hospital
New York, New York, United States
Albert Einstein College of Medicine
The Bronx, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
University of North Carolina Diabetes Care Center
Durham, North Carolina, United States
University of Cincinnati
Cincinnati, Ohio, United States
Case Western Reserve University School of Medicine
Cleveland, Ohio, United States
Kaiser Permanente Northwest
Portland, Oregon, United States
Oregon Health and Science University
Portland, Oregon, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
Baylor Endocrine Center
Dallas, Texas, United States
University of Texas-Southwestern Medical Center
Dallas, Texas, United States
Baylor College of Medicine
Houston, Texas, United States
University of Texas Health Science Center
San Antonio, Texas, United States
Seattle Institute for Biomedical and Clinical Research
Seattle, Washington, United States
Ghosh A, Chan W, Younes N, Davis BR. A Dynamic Risk Model for Multitype Recurrent Events. Am J Epidemiol. 2023 Apr 6;192(4):621-631. doi: 10.1093/aje/kwac213.
Lachin JM, Bebu I. Closed testing of each group versus the others combined in a multiple group analysis. Clin Trials. 2020 Feb;17(1):77-86. doi: 10.1177/1740774519879932. Epub 2019 Oct 24.
Bebu I, Lachin JM. Properties of composite time to first event versus joint marginal analyses of multiple outcomes. Stat Med. 2018 Nov 30;37(27):3918-3930. doi: 10.1002/sim.7849. Epub 2018 Jun 28.
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Lachin JM. Applications of the Wei-Lachin multivariate one-sided test for multiple outcomes on possibly different scales. PLoS One. 2014 Oct 17;9(10):e108784. doi: 10.1371/journal.pone.0108784. eCollection 2014.
Lachin JM. Fallacies of last observation carried forward analyses. Clin Trials. 2016 Apr;13(2):161-8. doi: 10.1177/1740774515602688. Epub 2015 Sep 22.
Pop-Busui R, Rosin SP, Butera NM, Krause-Steinrauf H, Abou Assi H, Garg RK, Inzucchi SE, Katona A, McGill JB, Mudaliar S, Schade DS, Seaquist ER, Tiktin M, Soliman EZ, Green JB; GRADE Research Group. Differences in Prevalence and Incidence of Electrocardiogram Abnormalities and Cardiovascular Autonomic Neuropathy Among Randomized Glucose-Lowering Treatments in Early Type 2 Diabetes: The Glycemia Reduction Approaches in Diabetes (GRADE) Cohort. Diabetes Care. 2025 Nov 1;48(11):1960-1970. doi: 10.2337/dc25-1087.
Presley CA, Butera NM, Krause-Steinrauf H, Desouza CV, Hollander PA, Hoogendoorn CJ, Lagari VS, Legowski EA, Martin CL, Rasouli N, Gonzalez JS, Cherrington AL. Lack of Association of Emotional Distress With Insulin Initiation in the GRADE Randomized Diabetes Comparative Effectiveness Trial. Sci Diabetes Self Manag Care. 2025 Aug;51(4):382-393. doi: 10.1177/26350106251361363. Epub 2025 Aug 1.
Hsia DS, Younes N, Ghosh A, Kazemi EJ, Krause-Steinrauf H, Buse JB, Baker C, Brown-Friday J, Diaz E, Diner J, Groessl EJ, Legowski EA, Mariash CN, Waltje AH, Wexler DJ, Martin CL; GRADE Research Group. Association of Hospitalizations With Randomized Glycemia-Lowering Treatment in GRADE. Diabetes Care. 2025 Jul 1;48(7):1288-1294. doi: 10.2337/dc24-2839.
Luchsinger JA, Rosin SP, Kazemi EJ, Younes N, Suratt CE, Fattaleh BN, Florez HJ, Gonzalez JS, Hollander P, Hox SH, Kuo S, Lee MS, Martens T, Pop-Busui R, Seaquist ER, Waltje AH, Barzilay JI; GRADE Research Group. Glucose-Lowering Medications, Glycemia, and Cognitive Outcomes: The GRADE Randomized Clinical Trial. JAMA Intern Med. 2025 Jul 1;185(7):778-787. doi: 10.1001/jamainternmed.2025.1189.
Wexler DJ, Garvey WT, Ghosh A, Kazemi EJ, Krause-Steinrauf H, Ahmann AJ, Brown-Friday J, Casula S, Cherrington AL, Elasy TA, Fortmann SP, Krakoff JA, Mudaliar S, Tiktin M, Younes N; GRADE Study Research Group. 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. Diabetes Care. 2025 Jun 1;48(6):935-944. doi: 10.2337/dc24-2825.
Utzschneider KM, Tripputi M, Butera NM, Mari A, Rosin SP, Banerji MA, Bergenstal RM, Brown N, Carlson AL, DeFronzo RA, Gramzinski MR, Harindhanavudhi T, Kozedub A, Sivitz WI, Steffes MW, Balasubramanyam A, Rasouli N; GRADE Research Group. Differential Treatment Effects on beta-Cell Function Using Model-Based Parameters in Type 2 Diabetes: Results From the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2025 Apr 1;48(4):623-631. doi: 10.2337/dc24-2419.
Nathan DM. Response to Comment on Nathan et al. Relationship Between Average Glucose Levels and HbA1c Differs Across Racial Groups: A Substudy of the GRADE Randomized Trial. Diabetes Care 2024;47:2155-2163. Diabetes Care. 2025 Mar 1;48(3):e34-e35. doi: 10.2337/dci24-0095. No abstract available.
Ehrmann D, Krause-Steinrauf H, Uschner D, Wen H, Hoogendoorn CJ, Crespo-Ramos G, Presley C, Arends VL, Cohen RM, Garvey WT, Martens T, Willis HJ, Cherrington A, Gonzalez JS; GRADE Research Group. Differential associations of somatic and cognitive-affective symptoms of depression with inflammation and insulin resistance: cross-sectional and longitudinal results from the Emotional Distress Sub-Study of the GRADE study. Diabetologia. 2025 Jul;68(7):1403-1415. doi: 10.1007/s00125-025-06369-8. Epub 2025 Feb 14.
Seaquist ER, Phillips LS, Ghosh A, Baker C, Bergenstal RM, Crandall JP, Goland RS, Gramzinski MR, Hox SH, Hsia DS, Johnson ML, Lachin JM, Raskin P, Valencia WM, Waltje AH, Younes N; GRADE Research Group. Glycemia reduction in type 2 diabetes-Hypoglycemia outcomes: A randomized clinical trial. PLoS One. 2024 Nov 15;19(11):e0309907. doi: 10.1371/journal.pone.0309907. eCollection 2024.
Nathan DM, Herman WH, Larkin ME, Krause-Steinrauf H, Abou Assi H, Ahmann AJ, Brown-Friday J, Hsia DS, Harindhanavudhi T, Johnson M, Arends VL, Butera NM, Rosin SP, Lachin JM, Younes N; GRADE Study Research Group. Relationship Between Average Glucose Levels and HbA1c Differs Across Racial Groups: A Substudy of the GRADE Randomized Trial. Diabetes Care. 2024 Dec 1;47(12):2155-2163. doi: 10.2337/dc24-1362.
Gonzalez JS, Bebu I, Krause-Steinrauf H, Hoogendoorn CJ, Crespo-Ramos G, Presley C, Naik AD, Kuo S, Johnson ML, Wexler D, Crandall JP, Bantle AE, Arends V, Cherrington AL; GRADE Research Group. Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2024 Apr 1;47(4):610-619. doi: 10.2337/dc23-2459.
Green JB, Everett BM, Ghosh A, Younes N, Krause-Steinrauf H, Barzilay J, Desouza C, Inzucchi SE, Pokharel Y, Schade D, Scrymgeour A, Tan MH, Utzschneider KM, Mudaliar S; GRADE Study Research Group. Cardiovascular Outcomes in GRADE (Glycemia Reduction Approaches in Type 2 Diabetes: A Comparative Effectiveness Study). Circulation. 2024 Mar 26;149(13):993-1003. doi: 10.1161/CIRCULATIONAHA.123.066604. Epub 2024 Feb 12.
Hampe CS, Shojaie A, Brooks-Worrell B, Dibay S, Utzschneider K, Kahn SE, Larkin ME, Johnson ML, Younes N, Rasouli N, Desouza C, Cohen RM, Park JY, Florez HJ, Valencia WM, Stempel R, Palmer JP, Balasubramanyam A. GAD65Abs Are Not Associated With Beta-Cell Dysfunction in Patients With T2D in the GRADE Study. J Endocr Soc. 2024 Feb 8;8(3):bvad179. doi: 10.1210/jendso/bvad179. eCollection 2024 Jan 16.
Hsia DS, Younes N, Krause-Steinrauf H, Kassem LS; GRADE Research Group. The incidence of retinopathy in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness study (GRADE). J Diabetes Complications. 2024 Mar;38(3):108692. doi: 10.1016/j.jdiacomp.2024.108692. Epub 2024 Feb 5.
Garvey WT, Cohen RM, Butera NM, Kazemi EJ, Younes N, Rosin SP, Suratt CE, Ahmann A, Hollander PA, Krakoff J, Martin CL, Seaquist E, Steffes MW, Lachin JM; GRADE Research Group. Association of Baseline Factors With Glycemic Outcomes in GRADE: A Comparative Effectiveness Randomized Clinical Trial. Diabetes Care. 2024 Apr 1;47(4):562-570. doi: 10.2337/dc23-1782.
Banerji MA, Buse JB, Younes N, Krause-Steinrauf H, Ghazi A, Lee M, Park J, Pop-Busui R, Underkofler C, Fortmann SP; GRADE Research Group. Mortality in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2024 Apr 1;47(4):589-593. doi: 10.2337/dc23-1356.
Cherrington AL, Bebu I, Krause-Steinrauf H, Hoogendoorn CJ, Crespo-Ramos G, Presley C, Naik AD, Balasubramanyam A, Gramzinski MR, Killean T, Arends VL, Gonzalez JS; GRADE Research Group. Does Emotional Distress Predict Worse Glycemic Control Over Time? Results From the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2024 Apr 1;47(4):620-628. doi: 10.2337/dc23-0642.
Hoogendoorn CJ, Krause-Steinrauf H, Uschner D, Wen H, Presley CA, Legowski EA, Naik AD, Golden SH, Arends VL, Brown-Friday J, Krakoff JA, Suratt CE, Waltje AH, Cherrington AL, Gonzalez JS; GRADE Research Group. Emotional Distress Predicts Reduced Type 2 Diabetes Treatment Adherence in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2024 Apr 1;47(4):629-637. doi: 10.2337/dc23-1401.
Rasouli N, Younes N, Ghosh A, Albu J, Cohen RM, DeFronzo RA, Diaz E, Sayyed Kassem L, Luchsinger JA, McGill JB, Sivitz WI, Tamborlane WV, Utzschneider KM, Kahn SE; GRADE Research Group. Longitudinal Effects of Glucose-Lowering Medications on beta-Cell Responses and Insulin Sensitivity in Type 2 Diabetes: The GRADE Randomized Clinical Trial. Diabetes Care. 2024 Apr 1;47(4):580-588. doi: 10.2337/dc23-1070.
Kirkman MS, Tripputi M, Krause-Steinrauf H, Bebu I, AbouAssi H, Burch H, Duran-Valdez E, Florez H, Garvey WT, Hsia DS, Salam M, Pop-Busui R; GRADE Research Group. Comparative Effects of Randomized Second-line Therapy for Type 2 Diabetes on a Composite Outcome Incorporating Glycemic Control, Body Weight, and Hypoglycemia: An Analysis of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2024 Apr 1;47(4):594-602. doi: 10.2337/dc23-1332.
Utzschneider KM, Younes N, Butera NM, Balasubramanyam A, Bergenstal RM, Barzilay J, DeSouza C, DeFronzo RA, Elasy T, Krakoff J, Kahn SE, Rasouli N, Valencia WM, Sivitz WI; GRADE Research Group. Impact of Insulin Sensitivity and beta-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. Diabetes Care. 2024 Apr 1;47(4):571-579. doi: 10.2337/dc23-1059.
Cherrington AL, Tripputi MT, Younes N, Herman WH, Katona A, Groessl EJ, Craig J, Gonzalez JS, Garg R, Casula S, Kuo S, Florez HJ; GRADE Research Group. Impact of Glucose-Lowering Medications on Health-Related Quality of Life in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2024 Apr 1;47(4):603-609. doi: 10.2337/dc23-1648.
Hollander PA, Krause-Steinrauf H, Butera NM, Kazemi EJ, Ahmann AJ, Fattaleh BN, Johnson ML, Killean T, Lagari VS, Larkin ME, Legowski EA, Rasouli N, Willis HJ, Martin CL; GRADE Research Group. The Use of Rescue Insulin in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2024 Apr 1;47(4):638-645. doi: 10.2337/dc23-0516.
Crespo-Ramos G, Bebu I, Krause-Steinrauf H, Hoogendoorn CJ, Fang R, Ehrmann D, Presley C, Naik AD, Katona A, Walker EA, Cherrington A, Gonzalez JS; GRADE Research Group. Emotional distress and cardiovascular disease risk among participants enrolled in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) study. Diabetes Res Clin Pract. 2023 Sep;203:110808. doi: 10.1016/j.diabres.2023.110808. Epub 2023 Jun 30.
Luchsinger JA, Kazemi EJ, Sanchez DL, Larkin ME, Valencia WM, Desouza C, Carlson AL, Pop-Busui R, Seaquist ER, Florez HJ, Barzilay J; GRADE Research Group. BMI, insulin sensitivity, and cognition in early type 2 diabetes: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study. Obesity (Silver Spring). 2023 Jul;31(7):1812-1824. doi: 10.1002/oby.23785.
Cherrington AL, Krause-Steinrauf H, Aroda V, Buse JB, Fattaleh B, Fortmann SP, Hall S, Hox SH, Kuhn A, Killean T, Loveland A, Phillips LS, Jackson AU, Waltje A, McKee MD; GRADE Research Group. Use of comprehensive recruitment strategies in the glycemia reduction approaches in diabetes: A comparative effectiveness study (GRADE) multi-center clinical trial. Clin Trials. 2023 Oct;20(5):546-558. doi: 10.1177/17407745231175919. Epub 2023 Jun 17.
Wexler DJ, de Boer IH, Ghosh A, Younes N, Bebu I, Inzucchi SE, McGill JB, Mudaliar S, Schade D, Steffes MW, Tamborlane WV, Tan MH, Ismail-Beigi F; GRADE Research Group. Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes: The GRADE Randomized Clinical Trial. JAMA Intern Med. 2023 Jul 1;183(7):705-714. doi: 10.1001/jamainternmed.2023.1487.
Gulanski BI, Butera NM, Krause-Steinrauf H, Lichtman JH, Harindhanavudhi T, Green JB, Suratt CE, AbouAssi H, Desouza C, Ahmann AJ, Wexler DJ, Aroda VR; GRADE Research Group. Higher burden of cardiometabolic and socioeconomic risk factors in women with type 2 diabetes: an analysis of the Glycemic Reduction Approaches in Diabetes (GRADE) baseline cohort. BMJ Open Diabetes Res Care. 2023 Apr;11(2):e003159. doi: 10.1136/bmjdrc-2022-003159.
Seegmiller JC, Schmit DJ, Arends VL, Steffes MW, Kahn SE, Younes N; GRADE Research Group. Assessment of circulating insulin using liquid chromatography-mass spectrometry during insulin glargine treatment in type 2 diabetes: Implications for estimating insulin sensitivity and beta-cell function. Diabetes Obes Metab. 2023 Jul;25(7):1995-2004. doi: 10.1111/dom.15072. Epub 2023 Apr 24.
Gonzalez JS, Krause-Steinrauf H, Bebu I, Crespo-Ramos G, Hoogendoorn CJ, Naik AD, Waltje A, Walker E, Ehrmann D, Brown-Friday J, Cherrington A; GRADE Research Group. Emotional distress, self-management, and glycemic control among participants enrolled in the glycemia reduction approaches in diabetes: A comparative effectiveness (GRADE) study. Diabetes Res Clin Pract. 2023 Feb;196:110229. doi: 10.1016/j.diabres.2022.110229. Epub 2022 Dec 20.
GRADE Study Research Group; Nathan DM, Lachin JM, Bebu I, Burch HB, Buse JB, Cherrington AL, Fortmann SP, Green JB, Kahn SE, Kirkman MS, Krause-Steinrauf H, Larkin ME, Phillips LS, Pop-Busui R, Steffes M, Tiktin M, Tripputi M, Wexler DJ, Younes N. Glycemia Reduction in Type 2 Diabetes - Microvascular and Cardiovascular Outcomes. N Engl J Med. 2022 Sep 22;387(12):1075-1088. doi: 10.1056/NEJMoa2200436.
GRADE Study Research Group; Nathan DM, Lachin JM, Balasubramanyam A, Burch HB, Buse JB, Butera NM, Cohen RM, Crandall JP, Kahn SE, Krause-Steinrauf H, Larkin ME, Rasouli N, Tiktin M, Wexler DJ, Younes N. Glycemia Reduction in Type 2 Diabetes - Glycemic Outcomes. N Engl J Med. 2022 Sep 22;387(12):1063-1074. doi: 10.1056/NEJMoa2200433.
Aroda VR, Krause-Steinrauf H, Kazemi EJ, Buse JB, Gulanski BI, Florez HJ, Ahmann AJ, Loveland A, Kuhn A, Lonier JY, Wexler DJ; GRADE Research Group. Clinical and Metabolic Characterization of Adults With Type 2 Diabetes by Age in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) Cohort. Diabetes Care. 2022 Jul;45(7):1512-1521. doi: 10.2337/dc21-2659. Epub 2022 Jun 13.
Florez HJ, Ghosh A, Pop-Busui R, Hox SH, Underkofler C, McKee MD, Park J, Rhee MK, Killean T, Krause-Steinrauf H, Aroda VR, Wexler DJ; GRADE Research Group. Differences in complications, cardiovascular risk factor, and diabetes management among participants enrolled at veterans affairs (VA) and non-VA medical centers in the glycemia reduction approaches in diabetes: A comparative effectiveness study (GRADE). Diabetes Res Clin Pract. 2022 Feb;184:109188. doi: 10.1016/j.diabres.2021.109188. Epub 2021 Dec 28.
Brooks-Worrell B, Hampe CS, Hattery EG, Palomino B, Zangeneh SZ, Utzschneider K, Kahn SE, Larkin ME, Johnson ML, Mather KJ, Younes N, Rasouli N, Desouza C, Cohen RM, Park JY, Florez HJ, Valencia WM; GRADE Beta-cell Ancillary Study Network; Shojaie A, Palmer JP, Balasubramanyam A. Islet Autoimmunity is Highly Prevalent and Associated With Diminished beta-Cell Function in Patients With Type 2 Diabetes in the Grade Study. Diabetes. 2022 Jan 21;71(6):1261-71. doi: 10.2337/db21-0590. Online ahead of print.
Nathan DM, Krause-Steinrauf H, Braffett BH, Arends VL, Younes N, McGee P, Lund C, Johnson M, Lorenzi G, Gao X, Steffes MW, Lachin JM; GRADE Research Group; DCCT/EDIC Research Group. Comparison of central laboratory HbA1c measurements obtained from a capillary collection versus a standard venous whole blood collection in the GRADE and EDIC studies. PLoS One. 2021 Nov 15;16(11):e0257154. doi: 10.1371/journal.pone.0257154. eCollection 2021.
Luchsinger JA, Younes N, Manly JJ, Barzilay J, Valencia W, Larkin ME, Falck-Ytter C, Krause-Steinrauf H, Pop-Busui R, Florez H, Seaquist E; GRADE Research Group; GRADE Research Group Investigators:. Association of Glycemia, Lipids, and Blood Pressure With Cognitive Performance in People With Type 2 Diabetes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2021 Oct;44(10):2286-2292. doi: 10.2337/dc20-2858. Epub 2021 Jul 20.
Barzilay JI, Ghosh A, Busui RP, Ahmann A, Balasubramanyam A, Banerji MA, Cohen RM, Green J, Ismail-Beigi F, Martin CL, Seaquist E, Luchsinger JA; GRADE Research Group. The cross-sectional association of cognition with diabetic peripheral and autonomic neuropathy-The GRADE study. J Diabetes Complications. 2021 Dec;35(12):108047. doi: 10.1016/j.jdiacomp.2021.108047. Epub 2021 Sep 15.
Cherrington AL, Krause-Steinrauf H, Bebu I, Naik AD, Walker E, Golden SH, Gonzalez JS; GRADE Research Group. Study of emotional distress in a comparative effectiveness trial of diabetes treatments: Rationale and design. Contemp Clin Trials. 2021 Aug;107:106366. doi: 10.1016/j.cct.2021.106366. Epub 2021 Mar 22.
Utzschneider KM, Younes N, Rasouli N, Barzilay JI, Banerji MA, Cohen RM, Gonzalez EV, Ismail-Beigi F, Mather KJ, Raskin P, Wexler DJ, Lachin JM, Kahn SE; GRADE Research Group. Shape of the OGTT glucose response curve: relationship with beta-cell function and differences by sex, race, and BMI in adults with early type 2 diabetes treated with metformin. BMJ Open Diabetes Res Care. 2021 Sep;9(1):e002264. doi: 10.1136/bmjdrc-2021-002264.
Utzschneider KM, Younes N, Rasouli N, Barzilay J, Banerji MA, Cohen RM, Gonzalez EV, Mather KJ, Ismail-Beigi F, Raskin P, Wexler DJ, Lachin JM, Kahn SE; GRADE Research Group. Association of glycemia with insulin sensitivity and beta-cell function in adults with early type 2 diabetes on metformin alone. J Diabetes Complications. 2021 May;35(5):107912. doi: 10.1016/j.jdiacomp.2021.107912. Epub 2021 Mar 17.
Barzilay JI, Younes N, Pop-Busui R, Florez H, Seaquist E, Falck-Ytter C, Luchsinger JA; GRADE Research Group. The cross-sectional association of renal dysfunction with tests of cognition in middle-aged adults with early type 2 diabetes: The GRADE Study. J Diabetes Complications. 2021 Mar;35(3):107805. doi: 10.1016/j.jdiacomp.2020.107805. Epub 2020 Nov 26.
Rasouli N, Younes N, Utzschneider KM, Inzucchi SE, Balasubramanyam A, Cherrington AL, Ismail-Beigi F, Cohen RM, Olson DE, DeFronzo RA, Herman WH, Lachin JM, Kahn SE; GRADE Research Group. Association of Baseline Characteristics With Insulin Sensitivity and beta-Cell Function in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) Study Cohort. Diabetes Care. 2021 Feb;44(2):340-349. doi: 10.2337/dc20-1787. Epub 2020 Dec 17.
Mather KJ, Bebu I, Baker C, Cohen RM, Crandall JP, DeSouza C, Green JB, Kirkman MS, Krause-Steinrauf H, Larkin M, Pettus J, Seaquist ER, Soliman EZ, Schroeder EB, Wexler DJ, Pop-Busui R; GRADE Research Group. Prevalence of microvascular and macrovascular disease in the Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) Study cohort. Diabetes Res Clin Pract. 2020 Jul;165:108235. doi: 10.1016/j.diabres.2020.108235. Epub 2020 May 23.
Sivitz WI, Phillips LS, Wexler DJ, Fortmann SP, Camp AW, Tiktin M, Perez M, Craig J, Hollander PA, Cherrington A, Aroda VR, Tan MH, Krakoff J, Rasouli N, Butera NM, Younes N; GRADE Research Group. Optimization of Metformin in the GRADE Cohort: Effect on Glycemia and Body Weight. Diabetes Care. 2020 May;43(5):940-947. doi: 10.2337/dc19-1769. Epub 2020 Mar 5.
Wexler DJ, Krause-Steinrauf H, Crandall JP, Florez HJ, Hox SH, Kuhn A, Sood A, Underkofler C, Aroda VR; GRADE Research Group. Baseline Characteristics of Randomized Participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE). Diabetes Care. 2019 Nov;42(11):2098-2107. doi: 10.2337/dc19-0901. Epub 2019 Aug 7.
Larkin ME, Nathan DM, Bebu I, Krause-Steinrauf H, Herman WH, Higgins JM, Tiktin M, Cohen RM, Lund C, Bergenstal RM, Johnson ML, Arends V; GRADE Research Group. Rationale and Design for a GRADE Substudy of Continuous Glucose Monitoring. Diabetes Technol Ther. 2019 Dec;21(12):682-690. doi: 10.1089/dia.2019.0202. Epub 2019 Sep 4.
Behringer-Massera S, Browne T, George G, Duran S, Cherrington A, McKee MD; GRADE Research Group. Facilitators and barriers to successful recruitment into a large comparative effectiveness trial: a qualitative study. J Comp Eff Res. 2019 Jul;8(10):815-826. doi: 10.2217/cer-2019-0010. Epub 2019 Aug 1.
Devchand R, Nicols C, Gallivan JM, Tiktin M, Krause-Steinrauf H, Larkin M, Tuncer DM; GRADE Research Group. Assessment of a National Diabetes Education Program diabetes management booklet: The GRADE experience. J Am Assoc Nurse Pract. 2017 May;29(5):255-263. doi: 10.1002/2327-6924.12445. Epub 2017 Feb 18.
Nathan DM, Buse JB, Kahn SE, Krause-Steinrauf H, Larkin ME, Staten M, Wexler D, Lachin JM; GRADE Study Research Group. Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care. 2013 Aug;36(8):2254-61. doi: 10.2337/dc13-0356. Epub 2013 May 20.
Li JH, Szczerbinski L, Tripputi M, Liu H, Nam S, Mujica E, Emmanouilidou A, Wangden TY, Citko-Rojewska A, Konopka P, Czajkowski M, Huerta-Chagoya A, Vora M, Leong A, Meigs JB, Ng MY, Loos RJF, Pigeyre M, Gerstein HC, Moura FA, Lai YP, Bhatt DL, Marston NA, Ruff CT, Sabatine MS, Dawed AY, Pearson ER, Satin LS, den Hoed M, Kretowski A, Kahn SE, Younes N, Mercader JM, Florez JC. Common genetic variants near SLC2A2 and glycemic response to glimepiride in the GRADE comparative effectiveness clinical trial. medRxiv [Preprint]. 2025 Oct 8:2025.10.07.25336827. doi: 10.1101/2025.10.07.25336827.
Natale P, Green SC, Tunnicliffe DJ, Pellegrino G, Toyama T, Strippoli GF. Glucagon-like peptide 1 (GLP-1) receptor agonists for people with chronic kidney disease and diabetes. Cochrane Database Syst Rev. 2025 Feb 18;2(2):CD015849. doi: 10.1002/14651858.CD015849.pub2.
El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.
Primary Completion
April 30, 2021
Actual (reported)Study Completion
April 30, 2021
Actual (reported)Last Updated
February 10, 2026
Results First Posted
February 10, 2026
Record last verified: 2026-01
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