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Impact of Insulin Sensitivity and β-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, ISSN: 1935-5548, Vol: 47, Issue: 4, Page: 571-579
2024
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New Findings from University of Washington Update Understanding of Antidiabetic Agents [Impact of Insulin Sensitivity and B-cell Function Over Time On Glycemic Outcomes In the Glycemia Reduction Approaches In Diabetes: a Comparative ...]

2024 DEC 03 (NewsRx) -- By a News Reporter-Staff News Editor at NewsRx Diabetes Daily -- Fresh data on Drugs and Therapies - Antidiabetic Agents

Article Description

OBJECTIVE To compare the effects of insulin sensitivity and β-cell function over time on HbA and durability of glycemic control in response to dual therapy. RESEARCH DESIGN AND METHODS GRADE participants were randomized to glimepiride (n = 1,254), liraglutide (n = 1,262), or sitagliptin (n = 1,268) added to baseline metformin and followed for mean ± SD 5.0 ± 1.3 years, with HbA assessed quarterly and oral glucose tolerance tests at baseline, 1, 3, and 5 years. We related time-varying insulin sensitivity (HOMA 2 of insulin sensitivity [HOMA2-%S]) and early (0–30 min) and total (0–120 min) C-peptide (CP) responses to changes in HbA and glycemic failure (primary outcome HbA ≥7% [53 mmol/mol] and secondary outcome HbA >7.5% [58 mmol/mol]) and examined differential treatment responses. RESULTS Higher HOMA2-%S was associated with greater initial HbA lowering (3 months) but not subsequent HbA rise. Greater CP responses were associated with a greater initial treatment response and slower subsequent HbA rise. Higher HOMA2-%S and CP responses were each associated with lower risk of primary and secondary outcomes. These associations differed by treatment. In the sitagliptin group, HOMA2-%S and CP responses had greater impact on initial HbA reduction (test of heterogeneity, P = 0.009 HOMA2-%S, P = 0.018 early CP, P = 0.001 total CP) and risk of primary outcome (P = 0.005 HOMA2-%S, P = 0.11 early CP, P = 0.025 total CP) but lesser impact on HbA rise (P = 0.175 HOMA2-%S, P = 0.006 early CP, P < 0.001 total CP) in comparisons with the glimepiride and liraglutide groups. There were no differential treatment effects on secondary outcome. CONCLUSIONS Insulin sensitivity and β-cell function affected treatment outcomes irrespective of drug assignment, with greater impact in the sitagliptin group on initial (short-term) HbA response in comparison with the glimepiride and liraglutide groups.

Bibliographic Details

Kristina M. Utzschneider; Naji Younes; Nicole M. Butera; Ashok Balasubramanyam; Richard M. Bergenstal; Joshua Barzilay; Cyrus DeSouza; Ralph A. DeFronzo; Tom Elasy; Jonathan Krakoff; Steven E. Kahn; Neda Rasouli; Willy M. Valencia; William I. Sivitz; 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; 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; 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

American Diabetes Association

Medicine; Nursing

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