Nick Freemantle1, Didac Mauricio2, Andrea Giaccari3, Timothy Bailey4, Ronan Roussel5,6,7, Denise Franco8, Baptiste Berthou9, Valerie Pilorget10, Jukka Westerbacka11, Zsolt Bosnyak11, Mireille Bonnemaire11, Anna M G Cali11, My-Liên Nguyên-Pascal10, Alfred Penfornis12, Manuel Perez-Maraver13, Jochen Seufert14, Sean D Sullivan15, John Wilding16, Carol Wysham17, Melanie Davies18. 1. Institute of Clinical Trials and Methodology, University College London, London, UK. 2. Department of Endocrinology & Nutrition, Hospital de la Santa Creu i Sant Pau, CIBERDEM, Barcelona, Spain. 3. Center for Endocrine and Metabolic Diseases, Fondazione Policlinico Universitario A. Gemelli IRCSS, Università Cattolica del Sacro Cuore, Rome, Italy. 4. AMCR Institute, Escondido, CA, USA. 5. Department of Diabetology, Endocrinology, and Nutrition, Bichat Hospital, AP-HP, Paris, France. 6. INSERM U1138, Centre de Recherche des Cordeliers, Paris, France. 7. UFR de Médecine, Paris University, Paris, France. 8. CPCLIN Clinical Research Center, São Paulo, Brazil. 9. IT&M Stats, Paris, France. 10. Sanofi, Chilly-Mazarin, France. 11. Sanofi, Paris, France. 12. Department of Diabetes, Sud-Francilien Hospital, Corbeil-Essonnes and Université Paris Sud, Paris, France. 13. Servei d´Endocrinologia i Nutrició, Hospital Universitari Bellvitge, L'Hospitalet de Llobregat, IDIBELL, Barcelona, Spain. 14. Faculty of Medicine, Division of Endocrinology and Diabetology, Department of Medicine II, University Hospital of Freiburg, University of Freiburg, Freiburg, Germany. 15. The CHOICE Institute, School of Pharmacy, University of Washington, Seattle, WA, USA. 16. Obesity and Endocrinology Clinical Research, Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK. 17. Diabetes and Endocrinology Center, Multicare Rockwood Clinic, Spokane, WA, USA. 18. Diabetes Research Centre, Leicester General Hospital, University of Leicester, Leicester, UK.
Abstract
Objective: To compare real-world outcomes with newer (insulin glargine 300U/mL; Gla-300) versus standard of care (SoC) basal insulins (BIs) in the REACH (insulin-naïve; NCT02967224) and REGAIN (basal insulin-treated; NCT02967211) studies in participants with uncontrolled type 2 diabetes (T2DM) in Europe and Brazil. Methods: In these open-label, parallel-group, pragmatic studies, patients (HbA1c > 7.0%) were randomized to Gla-300 or SoC BI for a 6-month treatment period (to demonstrate non-inferiority of Gla-300 vs SoC BIs for HbA1c change [non-inferiority margin 0.3%]) and a 6-month extension period (continuing with their assigned treatment). Insulin titration/other medication changes were at investigator/patient discretion post-randomization. Results: Overall, 703 patients were randomized to treatment in REACH (Gla-300, n = 352; SoC, n = 351) and 609 (Gla-300, n = 305, SoC, n = 304) in REGAIN. The primary outcome, non-inferiority of Gla-300 versus SoC for HbA1c change from baseline to month 6, was met in REACH (least squares [LS] mean difference 0.12% [95% CI -0.046 to 0.281]) but not REGAIN (LS mean difference 0.17% [0.015-0.329]); no between-treatment difference in HbA1c change was shown after 12 months in either study. BI dose increased minimally from baseline to 12 months in REACH (Gla-300, +0.17 U/kg; SoC, +0.15 U/kg) and REGAIN (Gla-300, +0.11 U/kg; SoC, +0.07 U/kg). Hypoglycemia incidence was low and similar between treatment arms in both studies.Conclusions: In both REACH and REGAIN, no differences in glycemic control or hypoglycemia outcomes with Gla-300 versus SoC BIs were seen over 12 months. However, the suboptimal insulin titration in REACH and REGAIN limits comparisons of outcomes between treatment arms and suggests that more titration instruction/support may be required for patients to fully derive the benefits from newer basal insulin formulations.
RCT Entities:
Objective: To compare real-world outcomes with newer (insulin glargine 300 U/mL; Gla-300) versus standard of care (SoC) basal insulins (BIs) in the REACH (insulin-naïve; NCT02967224) and REGAIN (basal insulin-treated; NCT02967211) studies in participants with uncontrolled type 2 diabetes (T2DM) in Europe and Brazil. Methods: In these open-label, parallel-group, pragmatic studies, patients (HbA1c > 7.0%) were randomized to Gla-300 or SoC BI for a 6-month treatment period (to demonstrate non-inferiority of Gla-300 vs SoC BIs for HbA1c change [non-inferiority margin 0.3%]) and a 6-month extension period (continuing with their assigned treatment). Insulin titration/other medication changes were at investigator/patient discretion post-randomization. Results: Overall, 703 patients were randomized to treatment in REACH (Gla-300, n = 352; SoC, n = 351) and 609 (Gla-300, n = 305, SoC, n = 304) in REGAIN. The primary outcome, non-inferiority of Gla-300 versus SoC for HbA1c change from baseline to month 6, was met in REACH (least squares [LS] mean difference 0.12% [95% CI -0.046 to 0.281]) but not REGAIN (LS mean difference 0.17% [0.015-0.329]); no between-treatment difference in HbA1c change was shown after 12 months in either study. BI dose increased minimally from baseline to 12 months in REACH (Gla-300, +0.17 U/kg; SoC, +0.15 U/kg) and REGAIN (Gla-300, +0.11 U/kg; SoC, +0.07 U/kg). Hypoglycemia incidence was low and similar between treatment arms in both studies.Conclusions: In both REACH and REGAIN, no differences in glycemic control or hypoglycemia outcomes with Gla-300 versus SoC BIs were seen over 12 months. However, the suboptimal insulin titration in REACH and REGAIN limits comparisons of outcomes between treatment arms and suggests that more titration instruction/support may be required for patients to fully derive the benefits from newer basal insulin formulations.
Entities:
Keywords:
Clinical trial; drug therapy; insulin; type 2 diabetes mellitus
Authors: Thomas Semlitsch; Jennifer Engler; Andrea Siebenhofer; Klaus Jeitler; Andrea Berghold; Karl Horvath Journal: Cochrane Database Syst Rev Date: 2020-11-09