Baseline Characteristics of Randomized Participants in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE)
Authors: Wexler Deborah J. , Krause-Steinrauf Heidi , Crandall Jill P. , Florez Hermes J. , Hox Sophia H. , Kuhn Alexander , Sood Ajay , Underkofler Chantal , Aroda Vanita R. ,   GRADE Research Group, Crandall Jill P. , McKee Melissa Diane , Brown-Friday Janet , Xhori Entila , Ballentine-Cargill Keisha , Duran Sally , Lukin Jennifer , Beringher Stephanie , Gonzalez de la Torre Susana , Phillips Lawrence , Burgess Elizabeth , Olson Darin , Rhee Mary , Wilson Peter , Raines Tasha Stephanie , Costello Julie , Gullett Chona , Maher-Albertelli Maxine , Morehead Folayan , Mungara Radhika , Person Saranjit , Savoye Louise , Sibymon Mabil , Tanukonda Sridhar , White Carol Ann , Holloway Leah , Adams Cynthia , Ross April , Balasubramanyam Ashok , Gonzalez Erica , Wright Charlyne , Hollander Priscilla , Roe Erin , Uy Analyn , Burt Polly , Estrada Lorie , Chionh Kris , Ismail-Beigi Faramarz , Falck-Ytter Corinna , Sayyed Kassem Laure , Sood Ajay , Tiktin Margaret , Cramer Bethany , Iacoboni Jacalyn , Kononets Maria V. , Kulow Tanya , Newman Cynthia , Stancil Katherine A. , Sanders Cristina , Tucker Lisa , Werner Amanda , Krol Adrienne , McPhee Gloria , Patel Christine , Colosimo Linda , Goland Robin , Pring James , Kringas Patricia , Tejada Jessica , Hausheer Camille , Schneier Harvey , Gumpel Kelly , Kirpitch Amanda , Green Jennifer B. , AbouAssi Hiba , Chatterjee Ranee , Feinglos Mark N. , English Jennifer , Jones Shubi A. , Khan Jeanne B. , Kimpel Ronna P. , Zimmer Mary , Furst Barbara M. , Satterwhite Connie R. , Thacker Kathryn , Evans Kreider Kieren J. , Mather Amale , Lteif Tonya , Hamilton Nick , Patel Gabriela , Riera Marcia , Jackson Vivian , Pirics Devin , Howard Danielle , Aguillar Sloan , Hurt Richard , Bergenstal Anders , Carlson Thomas , Martens Mary , Johnson Renae , Hill Jamie , Hyatt Connie , Jensen Marcia , Madden Dianna , Martin Holly , Willis Wanda , Konerza Rebecca , Passi Kathleen , Kleeberger Stephen , Fortmann Michael , Herson Karen , Mularski Harry , Glauber James , Prihoda Britt , Ash Christina , Carlson Phyllis Anne , Ramey Emily , Schield Britta , Torgrimson-Ojerio Kathy , Arnold Bryan , Kauffman Elease , Panos Samantha , Sahnow Kristi , Bays Jennifer , Cook Jennifer , Gluth Debra , Sasaki Katrina , Schell Jennifer , Criscola Camille , Friason Suzi , Jones Sergey , Nazarov Joshua , Barzilay Negah , Rassouli Rachel , Puttnam Michelle , Curtis Kia , Stokes Bonita , Hollis Cynthia , Sanders-Jones Roslin , Nelson Zakiah , El-Haqq Abby , Kolli Tu , Tran Deborah , Wexler James , Meigs Amy , Dushkin Gianna , Rocchio Brittany , Chambers Mike , Yepes Barbara , Steiner Hilary , Dulin Melody , Cayford Andrea , DeManbey Lindsey , Gurry Mallory , Hillard Kimberly , Martin Christine , Stevens Nopporn , Thangthaeng Raquel , Kochis Elyse , Raymond Valerie , Ripley Jean , Park Vanita , Aroda Adline , Ghazi Amy , Loveland Maria , Hurtado Alexander , Kuhn Florence , Mofor Hermes J. , Florez Willy Marcos , Valencia Jennifer , Marks Lisset , Oropesa-Gonzalez Ana K. , Riccio  , Veliz Ramfis , Nieto-Martinez Miriam , Gutt Andrew , Ahmann Diana , Aby-Daniel Farahnaz , Joarder Victoria , Morimoto Carol , Sprague Daisuke , Yamashita Nancy , Cady Patricia , Kirchhoff Nadia , Rivera-Eschright Joseph , Adducci Brianna , Morales Gomez Alina , Goncharova Sophia H. , Hox Helen , Petrovitch Michael , Matwichyna Victoria , Jenkins Nina O. , Bermudez Renée R. , Ishii Daniel S. , Hsia William T. , Cefalu Frank L. , Greenway Celeste , Waguespack Erin , King Natalie , Haynes Amy , Thomassie Brandi , Bourgeois Claire , Hazlett Robert , Henry Sunder , Mudaliar Schafer , Boeder Jeremy , Pettus Elsa , Diaz Catherine , DeLue Erick , Castro Sylvia , Hernandez Jonathan , Krakoff Jeffrey M. , Curtis Tina , Killean Erica , Joshevama Enrique , Diaz Denelle , Martin Tracey , Karshner Jeanine , Albu F. Xavier , Pi-Sunyer Sylvaine , Frances Carol , Maggio Emily , Ellis Joseph , Bastawrose Xiuqun , Gong Mary Ann , Banerji Phyllis , August Daniel , Lorber Necole M. , Brown Debra H. , Josephson Lorraine L. , Thomas Mari , Tsovian Ajini , Cherian Marlo H. , Jacobson Motria M. , Mishko M. Sue , Kirkman Katherine , Bergamo John B. , Buse Jean , Dostou Laura , Young April , Goley Jeffrey , Kerr Joseph F. , Largay Sonia , Guarda Juanita , Cuffee Dawn , Culmer Rachael , Fraser Hope , Almeida Samantha , Coffer Elizabeth , Debnam Lauren , Kiker Sarah , Morton Kim , Josey Gail , Fuller W. Timothy , Garvey Andrea , Cherrington Dana , Golson Olivia , Griffith Mary Catherine , Robertson April , Agne Steve , McCullars Robert M. , Cohen Jacqueline , Craig Kimberly , Kersey M. Colleen , Rogge Carla , Wilson Kathryn , Burton Sonia , Lipp Mary Beth , Vonder Meulen Neda , Rasouli Emily , Schroeder Stephanie , Steiner Chelsea , Baker Chantal , Underkofler Sara , Douglass William , Sivitz Erin , Cline Laura , Knosp Jennifer , McConnell Tamara , Lowe William H. , Herman Rodica , Pop-Busui Meng H. , Tan Catherine , Martin Andrea , Waltje Lynn , Goodhall Rebecca , Eggleston Shihchen , Kuo Stephanie , Bule Nancy , Kessler Elizabeth , LaSalle Elizabeth R. , Seaquist Anne , Bantle Anjali , Kumar Bruce , Redmon John , Bantle Tasma , Harindhanavudhi Mary , Coe Michael , Mech Abdisa , Taddese Lesia , Lesne Shannon , Smith Cyrus , Desouza Lisa , Kuechenmeister Vijay , Shivaswamy Ana Laura , Morales Maria Grace , Rodriguez Kris , Seipel Alissa , Alfred Jenna , Eggert Grace , Lord William , Taylor Renee , Tillson David S. , Schade Allen , Adolphe Mark , Burge Elizabeth , Duran-Valdez Janae , Martinez Doris , Hernandez  , McGinnis Benjamin , Pucchetti Elizabeth , Scripsick Ralph A. , DeFronzo Eugenio , Cersosimo Muhammad , Abdul-Ghani Curtis , Triplitt Hector , Verastiqui Rosa Irene , Garza Kathryn , Wright Curtiss , Puckett Philip , Raskin Chanhaeng , Rhee Soma , Abraham Lin Fan , Jordan Serey , Sao Luisa , Morton Oralenda , Smith Laura , Osornio Walker Laura , Schnurr-Breen Rosa , Ayala Robert Brian , Kraymer Daytheon , Sturgess Kristina M. , Utzschneider Steven E. , Kahn Lorena , Alarcon-Casas Wright Edward J. , Boyko Elaine C. , Tsai Dace L. , Trence Basma N. , Fattaleh Brenda K. , Montgomery Karen M. , Atkinson Tessa , Concepcion Alexandra , Kozedub Cameron , Moak Samantha , Rhothisen Tom A. , Elasy Stephanie , Martin Laura , Shackelford Rita , Goidel Nina , Hinkle Janie , Lipps Hogan Cynthia , Lovell Janet , Myers Janet B. , McGill Maamoun , Salam Sarah , Kissel Toni , Schweiger Carol , Recklein William , Tamborlane Patricia , Gatcomb Anne , Camp Barbara , Gulanski Silvio , Inzucchi Kim , Pham Michele , Alguard Katarzyna , Lessard Magalys , Perez Elizabeth , Magenheimer Abmaridel , Montoza David M. , Nathan John , Lachin Heidi , Krause-Steinrauf Mary , Larkin Henry B. , Burch Barbara , Linder Andrew , Bremer Naji , Younes Michael , Backman Ionut , Bebu C.J. , Buys Anna , Fagan Murphy Yuping , Gao Michaela , Gramzinski Stephanie , Hall Elizabeth , Legowski Alyssa , Arey Joel , Bethepu Claire , Lund Pam , Mangat  , Dhaliwal Paula , McGee Emily , Mesimer Lisa , Ngo Michael , Steffes Jesse , Seegmiller Amy , Saenger Valerie , Arends Deanna , Gabrielson Todd , Conner Stuart , Warren Jolene , Day Alexandra , Scrymgeour Elsayed Z. , Soliman Zhu-Ming , Zhang Charles , Campbell Julie , Hu Lisa , Keasler Susan , Hensley Yabing , Li Rada , Mihalcea Veronica , Perez-Rosas Lisa , Prosser Kenneth , Resnicow Wen , Ye Hui , Shao Ping , Zhang Jose , Luchsinger Danurys , Sanchez Judith , Fradkin Erik , Groessl Helen , Chong Naomi , Hillery Ivan , Abdouch Paula , Brantley Frances E. , Broyles Gay , Canaris Paul , Copeland Jeri J. , Craine Warren L. , Fein Melissa S. , Lee Rebecca , Meiners Vaughn , Meiners Hollis , O’Neal James E. , Park Edward , Sledge Jeanne , Steppel-Resnick Alexander , Turchin Barbara , Brooks-Worrell Christiane S. , Hampe Christopher B. , Newgard Jerry P. , Palmer Ali , Shojaie John , Higgins Lawrence , Fischer Sherita , Golden Jeffery , Gonzalez Aanand , Naik Elizabeth , Walker Lynne , Doner Lotenberg Joanne M. , Gallivan Joanne , Lim Diane M. , Tuncer  , Behringer-Massera Stephanie 
Published: August 2019

OBJECTIVE
GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) is a 36-center unmasked, parallel treatment group, randomized controlled trial evaluating four diabetes medications added to metformin in people with type 2 diabetes (T2DM). We report baseline characteristics and compare GRADE participants to a National Health and Nutrition Examination Survey (NHANES) cohort.

RESEARCH DESIGN AND METHODS
Participants were age ≥30 years at the time of diagnosis, with duration of T2DM &lt;10 years, HbA1c 6.8–8.5% (51–69 mmol/mol), prescribed metformin monotherapy, and randomized to glimepiride, sitagliptin, liraglutide, or insulin glargine.

RESULTS
At baseline, GRADE’s 5,047 randomized participants were 57.2 ± 10.0 years of age, 63.6% male, with racial/ethnic breakdown of 65.7% white, 19.8% African American, 3.6% Asian, 2.7% Native American, 7.6% other or unknown, and 18.4% Hispanic/Latino. Duration of diabetes was 4.2 ± 2.8 years, with mean HbA1c of 7.5 ± 0.5% (58 ± 5.3 mmol/mol), BMI of 34.3 ± 6.8 kg/m2, and metformin dose of 1,944 ± 204 mg/day. Among the cohort, 67% reported a history of hypertension, 72% a history of hyperlipidemia, and 6.5% a history of heart attack or stroke. Applying GRADE inclusion criteria to NHANES indicates enrollment of a representative cohort with T2DM on metformin monotherapy (NHANES cohort average age, 57.9 years; mean HbA1c, 7.4% [57 mmol/mol]; BMI, 33.2 kg/m2; duration, 4.2 ± 2.5 years; and 7.2% with a history of cardiovascular disease).

CONCLUSIONS
The GRADE cohort represents patients with T2DM treated with metformin requiring a second diabetes medication. GRADE will inform decisions about the clinical effectiveness of the addition of four classes of diabetes medications to metformin.