Long-term Benefits of Intensive Glucose Control for Preventing End-Stage Kidney Disease: ADVANCE-ON.

Abstract

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.

• Authors: Muh Geot Wong, Vlado Perkovic, John Chalmers, Mark Woodward, Qiang Li, Mark E Cooper, Pavel Hamet, Stephen Harrap, Simon Heller, Stephen MacMahon, Giuseppe Mancia, Michel Marre, David Matthews, Bruce Neal, Neil Poulter, Anthony Rodgers, Bryan Williams, Sophia Zoungas, ADVANCE-ON Collaborative Group
• Journal: Diabetes care (Diabetes Care) Vol. 39 Issue 5 Pg. 694-700 (May 2016) ISSN: 1935-5548 [Electronic] United States
• PMID: 27006512 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Chemical References

• Antihypertensive Agents
• Blood Glucose
• Drug Combinations
• Glycated Hemoglobin A
• Hypoglycemic Agents
• indapamide, perindopril drug combination
• Indapamide
• Gliclazide
• Perindopril

Topics

• Aged
• Antihypertensive Agents (therapeutic use)
• Blood Glucose (metabolism)
• Blood Pressure (drug effects)
• Diabetes Mellitus, Type 2 (blood, drug therapy)
• Drug Combinations
• Female
• Follow-Up Studies
• Gliclazide (therapeutic use)
• Glycated Hemoglobin (metabolism)
• Humans
• Hypoglycemia (drug therapy)
• Hypoglycemic Agents (therapeutic use)
• Indapamide (therapeutic use)
• Kidney Failure, Chronic (blood, prevention & control)
• Male
• Middle Aged
• Perindopril (therapeutic use)
• Treatment Outcome