Background: In the AWARD-7 trial of participants with type 2 diabetes (T2DM) and moderate-to-severe CKD, dulaglutide (DU) treatment slowed decline in eGFR compared with insulin glargine (IG). Treatment with doses of either DU or IG resulted in similar levels of glycemic control and BP. The aim of this analysis was to determine the risk of clinical event outcomes between treatment groups. Methods: Participants with T2DM and CKD categories 3-4 were randomized (1:1:1) to 0.75 or 1.5 mg DU weekly or IG daily as basal therapy, with titrated insulin lispro, for 1 year. The time to occurrence of the composite outcome of ≥40% eGFR decline, ESKD, or death due to kidney disease was compared using a Cox proportional-hazards model. Results: Patients treated with 1.5 mg DU weekly versus IG daily for 1 year had a lower risk of ≥40% eGFR decline or ESKD events in the overall study population (5% versus 11%; hazard ratio, 0.45; 95% CI, 0.20 to 0.97; P=0.04). Most events occurred in the subset of patients with macroalbuminuria, where risk of the composite outcome was substantially lower for 1.5 mg DU versus IG (7% versus 22%; hazard ratio, 0.25; 95% CI, 0.10 to 0.68; P=0.006). No deaths due to kidney disease occurred. Conclusions: Treatment with 1.5 mg DU weekly was associated with a clinically relevant risk reduction of ≥40% eGFR decline or ESKD compared with IG daily, particularly in the macroalbuminuria subgroup of participants with T2DM and moderate-to-severe CKD.
Background: In the AWARD-7 trial of participants with type 2 diabetes (T2DM) and moderate-to-severe CKD, dulaglutide (DU) treatment slowed decline in eGFR compared with insulin glargine (IG). Treatment with doses of either DU or IG resulted in similar levels of glycemic control and BP. The aim of this analysis was to determine the risk of clinical event outcomes between treatment groups. Methods: Participants with T2DM and CKD categories 3-4 were randomized (1:1:1) to 0.75 or 1.5 mg DU weekly or IG daily as basal therapy, with titrated insulin lispro, for 1 year. The time to occurrence of the composite outcome of ≥40% eGFR decline, ESKD, or death due to kidney disease was compared using a Cox proportional-hazards model. Results: Patients treated with 1.5 mg DU weekly versus IG daily for 1 year had a lower risk of ≥40% eGFR decline or ESKD events in the overall study population (5% versus 11%; hazard ratio, 0.45; 95% CI, 0.20 to 0.97; P=0.04). Most events occurred in the subset of patients with macroalbuminuria, where risk of the composite outcome was substantially lower for 1.5 mg DU versus IG (7% versus 22%; hazard ratio, 0.25; 95% CI, 0.10 to 0.68; P=0.006). No deaths due to kidney disease occurred. Conclusions: Treatment with 1.5 mg DU weekly was associated with a clinically relevant risk reduction of ≥40% eGFR decline or ESKD compared with IG daily, particularly in the macroalbuminuria subgroup of participants with T2DM and moderate-to-severe CKD.
Authors: Steven P Marso; Stephen C Bain; Agostino Consoli; Freddy G Eliaschewitz; Esteban Jódar; Lawrence A Leiter; Ildiko Lingvay; Julio Rosenstock; Jochen Seufert; Mark L Warren; Vincent Woo; Oluf Hansen; Anders G Holst; Jonas Pettersson; Tina Vilsbøll Journal: N Engl J Med Date: 2016-09-15 Impact factor: 91.245
Authors: Katherine R Tuttle; Cory Heilmann; Byron J Hoogwerf; Carl Brown; Pamela W Anderson Journal: Am J Kidney Dis Date: 2013-05-16 Impact factor: 8.860
Authors: Andrew S Levey; Ron T Gansevoort; Josef Coresh; Lesley A Inker; Hiddo L Heerspink; Morgan E Grams; Tom Greene; Hocine Tighiouart; Kunihiro Matsushita; Shoshana H Ballew; Yingying Sang; Edward Vonesh; Jian Ying; Tom Manley; Dick de Zeeuw; Kai-Uwe Eckardt; Adeera Levin; Vlado Perkovic; Luxia Zhang; Kerry Willis Journal: Am J Kidney Dis Date: 2019-08-28 Impact factor: 8.860
Authors: Toshiharu Ninomiya; Vlado Perkovic; Bastiaan E de Galan; Sophia Zoungas; Avinesh Pillai; Meg Jardine; Anushka Patel; Alan Cass; Bruce Neal; Neil Poulter; Carl-Erik Mogensen; Mark Cooper; Michel Marre; Bryan Williams; Pavel Hamet; Giuseppe Mancia; Mark Woodward; Stephen Macmahon; John Chalmers Journal: J Am Soc Nephrol Date: 2009-05-14 Impact factor: 10.121
Authors: Manjiri Pawaskar; Katherine R Tuttle; Qian Li; Jennie H Best; Pamela W Anderson Journal: Ann Pharmacother Date: 2014-02-04 Impact factor: 3.154
Authors: Michaël J B van Baar; Annemarie B van der Aart; Klaas Hoogenberg; Jaap A Joles; Hiddo J L Heerspink; Daniël H van Raalte Journal: Ther Adv Endocrinol Metab Date: 2019-07-24 Impact factor: 3.565