TY - JOUR
T1 - Long-term benefits of intensive glucose Control for preventing end-stage kidney disease
T2 - ADVANCE-ON
AU - Wong, Muh Geot
AU - Perkovic, Vlado
AU - Chalmers, John
AU - Woodward, Mark
AU - Li, Qiang
AU - Cooper, Mark E.
AU - Hamet, Pavel
AU - Harrap, Stephen
AU - Heller, Simon
AU - Macmahon, Stephen
AU - Mancia, Giuseppe
AU - Marre, Michel
AU - Matthews, David
AU - Neal, Bruce
AU - Poulter, Neil
AU - Rodgers, Anthony
AU - Williams, Bryan
AU - Zoungas, Sophia
N1 - Funding Information:
The ADVANCE trial and ADVANCE-ON follow-up study were funded by unrestricted grants from Servier and the Australia National Health and Medical Research Council. M.G.W. reports fees for scientific lectures from AstraZeneca. V.P. reports honoraria for scientific lectures from Boehringer Ingelheim, Merck, AbbVie, Roche, AstraZeneca, and Servier and serves on steering committees and/or advisory boards supported by AbbVie,Astellas, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and Pfizer. J.C. reports research grants administered through the University of Sydney for the ADVANCE trial and the ADVANCE-ON posttrial study and honoraria from Servier for speaking about these studies at scientific meetings. P.H. is a member of Coll?ge International de Recherche Servier. B.W. has received honoraria from Servier for lecturesat scientific meetings. S.Z. reports past participation in advisory boards and/or receiving honoraria from Amgen Australia, AstraZeneca/Bristol-Myers Squibb Australia, Janssen-Cilag, Merck Sharp & Dohme (Australia), Novartis Australia, Sanofi, Servier Laboratories, and Takeda Australia as well as Monash University undertaking contract work for AstraZeneca Pty Ltd./Bristol-Myers Squibb Australia Pty Ltd. No other potential conflicts of interest relevant to this article were reported.
Publisher Copyright:
© 2016 by the American Diabetes Association.
PY - 2016/5
Y1 - 2016/5
N2 - OBJECTIVE: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial reported that intensive glucose control prevents end-stage kidney disease (ESKD) in patients with type 2 diabetes, but uncertainty about the balance between risks and benefits exists. Here, we examine the long-term effects of intensive glucose control on risk of ESKD and other outcomes. RESEARCH DESIGN AND METHODS: Survivors, previously randomized to intensive or standard glucose control, were invited to participate in post-trial follow-up. ESKD, defined as the need for dialysis or kidney transplantation, or death due to kidney disease, was documented overall and by baseline CKD stage, along with hypoglycemic episodes, major cardiovascular events, and death from other causes. RESULTS: A total of 8,494 ADVANCE participants were followed for a median of 5.4 additional years. In-trial HbA1c differences disappeared by the first post-trial visit. The in-trial reductions in the risk of ESKD (7 vs. 20 events, hazard ratio [HR] 0.35, P = 0.02) persisted after 9.9 years of overall follow-up (29 vs. 53 events, HR 0.54, P < 0.01). These effects were greater in earlier-stage CKD (P = 0.04) and at lower baseline systolic blood pressure levels (P = 0.01). The effects of glucose lowering on the risks of death, cardiovascular death, or major cardiovascular events did not differ by levels of kidney function (P > 0.26). CONCLUSIONS: Intensive glucose control was associated with a long-term reduction in ESKD, without evidence of any increased risk of cardiovascular events or death. These benefits were greater with preserved kidney function and with well-controlled blood pressure.
AB - OBJECTIVE: The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial reported that intensive glucose control prevents end-stage kidney disease (ESKD) in patients with type 2 diabetes, but uncertainty about the balance between risks and benefits exists. Here, we examine the long-term effects of intensive glucose control on risk of ESKD and other outcomes. RESEARCH DESIGN AND METHODS: Survivors, previously randomized to intensive or standard glucose control, were invited to participate in post-trial follow-up. ESKD, defined as the need for dialysis or kidney transplantation, or death due to kidney disease, was documented overall and by baseline CKD stage, along with hypoglycemic episodes, major cardiovascular events, and death from other causes. RESULTS: A total of 8,494 ADVANCE participants were followed for a median of 5.4 additional years. In-trial HbA1c differences disappeared by the first post-trial visit. The in-trial reductions in the risk of ESKD (7 vs. 20 events, hazard ratio [HR] 0.35, P = 0.02) persisted after 9.9 years of overall follow-up (29 vs. 53 events, HR 0.54, P < 0.01). These effects were greater in earlier-stage CKD (P = 0.04) and at lower baseline systolic blood pressure levels (P = 0.01). The effects of glucose lowering on the risks of death, cardiovascular death, or major cardiovascular events did not differ by levels of kidney function (P > 0.26). CONCLUSIONS: Intensive glucose control was associated with a long-term reduction in ESKD, without evidence of any increased risk of cardiovascular events or death. These benefits were greater with preserved kidney function and with well-controlled blood pressure.
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U2 - 10.2337/dc15-2322
DO - 10.2337/dc15-2322
M3 - Article
C2 - 27006512
AN - SCOPUS:84964733198
VL - 39
SP - 694
EP - 700
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 5
ER -