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)
Authors: Jeffrey S. Gonzalez, Ionut Bebu, Heidi Krause-Steinrauf, Claire J. Hoogendoorn, Gladys Crespo-Ramos, Caroline Presley, Aanand D. Naik, Shihchen Kuo, Mary L. Johnson, Deborah Wexler, Jill P. Crandall, Anne E. Bantle, Valerie Arends, Andrea L. Cherrington, J.P. Crandall, M.D. McKee, S. Behringer-Massera, J. Brown-Friday, E. Xhori, K. Ballentine-Cargill, S. Duran, H. Estrella, S. Gonzalez de la torre, J. Lukin, L.S. Phillips, E. Burgess, D. Olson, M. Rhee, P. Wilson, T.S. Raines, J. Boers, J. Costello, M. Maher-Albertelli, R. Mungara, L. Savoye, C.A. White, C. Gullett, L. Holloway, F. Morehead, S. Person, M. Sibymon, S. Tanukonda, C. Adams, A. Ross, A. Balasubramanyam, R. Gaba, E. Gonzalez Hattery, A. Ideozu, J. Jimenez, G. Montes, C. Wright, P. Hollander, E. Roe, A. Jackson, A. Smiley, P. Burt, L. Estrada, K. Chionh, F. Ismail-Beigi, C. Falck-Ytter, L. Sayyed Kassem, A. Sood, M. Tiktin, T. Kulow, C. Newman, K.A. Stancil, B. Cramer, J. Iacoboni, M.V. Kononets, C. Sanders, L. Tucker, A. Werner, A. Maxwell, G. McPhee, C. Patel, L. Colosimo, A. Krol, R. Goland, J. Pring, L. Alfano, P. Kringas, C. Hausheer, J. Tejada, K. Gumpel, A. Kirpitch, H. Schneier, J.B. Green, H. AbouAssi, R. Chatterjee, M.N. Feinglos, J. English Jones, S.A. Khan, J.B. Kimpel, R.P. Zimmer, M. Furst, B.M. Satterwhite, C.R. Thacker, K. Evans Kreider, C.N. Mariash, K.J. Mather, H.M. Ismail, A. Lteif, M. Mullen, T. Hamilton, N. Patel, G. Riera, M. Jackson, V. Pirics, D. Aguillar, D. Howard, S. Hurt, R. Bergenstal, A. Carlson, T. Martens, M. Johnson, R. Hill, J. Hyatt, C. Jensen, M. Madden, D. Martin, H. Willis, W. Konerza, S. Yang, K. Kleeberger, R. Passi, S. Fortmann, M. Herson, K. Mularski, H. Glauber, J. Prihoda, B. Ash, C. Carlson, P.A. Ramey, E. Schield, B. Torgrimson-Ojerio, K. Arnold, B. Kauffman, E. Panos, S. Sahnow, K. Bays, K. Berame, J. Cook, D. Ghioni, J. Gluth, K. Schell, J. Criscola, C. Friason, S. Jones, S. Nazarov, J. Barzilay, N. Rassouli, R. Puttnam, B. Ojoawo, R. Nelson, M. Curtis, B. Hollis, C. Sanders-Jones, K. Stokes, Z. El-Haqq, A. Kolli, T. Tran, D. Wexler, M.E. Larkin, J. Meigs, B. Chambers, A. Dushkin, G. Rocchio, M. Yepes, B. Steiner, H. Dulin, M. Cayford, K. Chu, A. DeManbey, M. Hillard, K. Martin, N. Thangthaeng, L. Gurry, R. Kochis, E. Raymond, V. Ripley, C. Stevens, J. Park, V. Aroda, A. Ghazi, M. Magee, A. Ressing, A. Loveland, M. Hamm, M. Hurtado, A. Kuhn, J. Leger, L. Manandhar, F. Mwicigi, O. Sanchez, T. Young, R. Garg, V. Lagari-Libhaber, H.J. Florez, W.M. Valencia, J. Marks, S. Casula, L. Oropesa-Gonzalez, L. Hue, A. Cuadot, R. Nieto-Martinez, A.K. Riccio Veliz, M. Gutt, Y.J. Kendal, B. Veciana, A. Ahmann, D. Aby-Daniel, F. Joarder, V. Morimoto, C. Sprague, D. Yamashita, N. Cady, N. Rivera-Eschright, P. Kirchhoff, B. Morales Gomez, J. Adducci, A. Goncharova, S.H. Hox, H. Petrovitch, M. Matwichyna, V. Jenkins, L. Broadwater, R.R. Ishii, N.O. Bermudez, D.S. Hsia, W.T. Cefalu, F.L. Greenway, C. Waguespack, E. King, G. Fry, A. Dragg, B. Gildersleeve, J. Arceneaux, N. Haynes, A. Thomassie, M. Pavlionis, B. Bourgeois, C. Hazlett, S. Mudaliar, R. Henry, S. Boeder, J. Pettus, E. Diaz, D. Garcia-Acosta, S. Maggs, C. DeLue, A. Stallings, E. Castro, S. Hernandez, J. Krakoff, J.M. Curtis, T. Killean, M. Khalid, E. Joshevama, E. Diaz, D. Martin, K. Tsingine, T. Karshner, J. Albu, F.X. Pi-Sunyer, S. Frances, C. Maggio, E. Ellis, J. Bastawrose, X. Gong, M.A. Banerji, P. August, M. Lee, D. Lorber, N.M. Brown, D.H. Josephson, L.L. Thomas, M. Tsovian, A. Cherian, M.H. Jacobson, M.M. Mishko, M.S. Kirkman, J.B. Buse, J. Diner, J. Dostou, S. Machineni, L. Young, K. Bergamo, A. Goley, J. Kerr, J.F. Largay, S. Guarda, J. Cuffee, D. Culmer, R. Fraser, H. Almeida, S. Coffer, E. Debnam, L. Kiker, S. Morton, K. Josey, G. Fuller, W.T. Garvey, A.L. Cherrington, D. Dyer, M.C.R. Lawson, O. Griffith, A. Agne, S. McCullars, R.M. Cohen, J. Craig, M.C. Rogge, K. Burton, K. Kersey, C. Wilson, S. Lipp, M.B. Vonder Meulen, C. Adkins, T. Onadeko, N. Rasouli, C. Baker, E. Schroeder, M. Razzaghi, C. Lyon, R. Penaloza, C. Underkofler, R. Lorch, S. Douglass, S. Steiner, W.I. Sivitz, E. Cline, L.K. Knosp, J. McConnell, T. Lowe, W.H. Herman, R. Pop-Busui, M.H. Tan, C. Martin, A. Waltje, A. Katona, L. Goodhall, R. Eggleston, S. Kuo, S. Bojescu, S. Bule, N. Kessler, E. LaSalle, K. Whitley, E.R. Seaquist, A. Bantle, T. Harindhanavudhi, A. Kumar, B. Redmon, J. Bantle, M. Coe, M. Mech, A. Taddese, K. Lesne, S. Smith, C. Desouza, L. Kuechenmeister, V. Shivaswamy, S. Burbach, M.G. Rodriguez, K. Seipel, A. Alfred, A.L. Morales, J. Eggert, G. Lord, W. Taylor, R. Tillson, D.S. Schade, A. Adolphe, M. Burge, E. Duran-Valdez, J. Martinez, A. Bancroft, S. Kunkel, F. Ali Jamaleddin Ahmad, D. Hernandez McGinnis, B. Pucchetti, E. Scripsick, A. Zamorano, R.A. DeFronzo, E. Cersosimo, M. Abdul-Ghani, C. Triplitt, D. Juarez, M. Mullen, R.I. Garza, H. Verastiqui, K. Wright, C. Puckett, P. Raskin, C. Rhee, S. Abraham, L.F. Jordan, S. Sao, L. Morton, O. Smith, L. Osornio Walker, L. Schnurr-Breen, R. Ayala, R.B. Kreymer, D. Sturgess, K.M. Utzschneider, S.E. Kahn, L. Alarcon-Casas Wright, E.J. Boyko, E.C. Tsai, D.L. Trence, S. Trikudanathan, B.N. Fattaleh, B.K. Montgomery, K.M. Atkinson, A. Kozedub, T. Concepcion, C. Moak, N. Prikhodko, S. Rhothisen, T.A. Elasy, S. Martin, L. Shackelford, R. Goidel, N. Hinkle, C. Lovell, J. Myers, J. Lipps Hogan, J.B. McGill, M. Salam, T. Schweiger, S. Kissel, C. Recklein, M.J. Clifton, W. Tamborlane, A. Camp, B. Gulanski, S.E. Inzucchi, K. Pham, M. Alguard, P. Gatcomb, K. Lessard, M. Perez, L. Iannone, E. Magenheimer, A. Montosa, J. Fradkin, H.B. Burch, A.A. Bremer, D.M. Nathan, J.M. Lachin, H. Krause-Steinrauf, N. Younes, I. Bebu, N. Butera, C.J. Buys, A. Fagan, Y. Gao, A. Ghosh, M.R. Gramzinski, S.D. Hall, E. Kazemi, E. Legowski, H. Liu, C. Suratt, M. Tripputi, A. Arey, M. Backman, J. Bethepu, C. Lund, P. Mangat Dhaliwal, P. McGee, E. Mesimer, L. Ngo, M. Steffes, J. Seegmiller, A. Saenger, V. Arends, D. Gabrielson, T. Conner, S. Warren, J. Day, J. Huminik, A. Scrymgeour, E.Z. Soliman, Y. Pokharel, Z.M. Zhang, C. Campbell, J. Hu, L. Keasler, S. Hensley, Y. Li, R. Mihalcea, D.J. Min, V. Perez-Rosas, L. Prosser, L. Resnicow, W. Ye, H. Shao, P. Zhang, J. Luchsinger, D. Sanchez, S. Assuras, E. Groessl, F. Sakha, H. Chong, N. Hillery, I. Abdouch, G. Bahtiyar, P. Brantley, F.E. Broyles, G. Canaris, P. Copeland, J.J. Craine, W.L. Fein, A. Gliwa, L. Hope, M.S. Lee, R. Meiners, V. Meiners, H. O’Neal, J.E. Park, A. Sacerdote, E. Sledge, L. Soni, J. Steppel-Reznik, A. Turchin, S. Golden, J. Gonzalez, A. Naik, E. Walker
Journal: Diabetes Care (2024)

OBJECTIVE We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments. RESEARCH DESIGN AND METHODS The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of &amp;lt;10 years’ duration, HbA1c 6.8–8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined differences at 1 year and over the 3-year follow-up. RESULTS Across treatments, diabetes distress (−0.24, P &amp;lt; 0.0001) and depressive symptoms (−0.67, P &amp;lt; 0.0001) decreased over 1 year. Diabetes distress was lower at 1 year for the glargine group than for the other groups combined (−0.10, P = 0.002). Diabetes distress was also lower for liraglutide than for glimepiride or sitagliptin (−0.10, P = 0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms. CONCLUSIONS Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress. Glargine lowered diabetes distress modestly at 1 year rather than increasing it. Liraglutide also reduced diabetes distress at 1 year. Results can inform treatment decisions for adults with early T2DM.