Follow-up of blood-pressure lowering and glucose control in type 2 diabetes

N Engl J Med. 2014 Oct 9;371(15):1392-406. doi: 10.1056/NEJMoa1407963. Epub 2014 Sep 19.

Abstract

Background: In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) factorial trial, the combination of perindopril and indapamide reduced mortality among patients with type 2 diabetes, but intensive glucose control, targeting a glycated hemoglobin level of less than 6.5%, did not. We now report results of the 6-year post-trial follow-up.

Methods: We invited surviving participants, who had previously been assigned to perindopril-indapamide or placebo and to intensive or standard glucose control (with the glucose-control comparison extending for an additional 6 months), to participate in a post-trial follow-up evaluation. The primary end points were death from any cause and major macrovascular events.

Results: The baseline characteristics were similar among the 11,140 patients who originally underwent randomization and the 8494 patients who participated in the post-trial follow-up for a median of 5.9 years (blood-pressure-lowering comparison) or 5.4 years (glucose-control comparison). Between-group differences in blood pressure and glycated hemoglobin levels during the trial were no longer evident by the first post-trial visit. The reductions in the risk of death from any cause and of death from cardiovascular causes that had been observed in the group receiving active blood-pressure-lowering treatment during the trial were attenuated but significant at the end of the post-trial follow-up; the hazard ratios were 0.91 (95% confidence interval [CI], 0.84 to 0.99; P=0.03) and 0.88 (95% CI, 0.77 to 0.99; P=0.04), respectively. No differences were observed during follow-up in the risk of death from any cause or major macrovascular events between the intensive-glucose-control group and the standard-glucose-control group; the hazard ratios were 1.00 (95% CI, 0.92 to 1.08) and 1.00 (95% CI, 0.92 to 1.08), respectively.

Conclusions: The benefits with respect to mortality that had been observed among patients originally assigned to blood-pressure-lowering therapy were attenuated but still evident at the end of follow-up. There was no evidence that intensive glucose control during the trial led to long-term benefits with respect to mortality or macrovascular events. (Funded by the National Health and Medical Research Council of Australia and others; ADVANCE-ON ClinicalTrials.gov number, NCT00949286.).

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / therapeutic use*
  • Blood Glucose
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / mortality
  • Drug Combinations
  • Female
  • Follow-Up Studies
  • Gliclazide / administration & dosage*
  • Glycated Hemoglobin A / analysis
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypoglycemic Agents / administration & dosage*
  • Indapamide / therapeutic use*
  • Male
  • Middle Aged
  • Perindopril / therapeutic use*
  • Risk Factors

Substances

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

Associated data

  • ClinicalTrials.gov/NCT00949286