Effect of a multifactorial intervention on mortality in type 2 diabetes

N Engl J Med. 2008 Feb 7;358(6):580-91. doi: 10.1056/NEJMoa0706245.

Abstract

Background: Intensified multifactorial intervention - with tight glucose regulation and the use of renin-angiotensin system blockers, aspirin, and lipid-lowering agents - has been shown to reduce the risk of nonfatal cardiovascular disease among patients with type 2 diabetes mellitus and microalbuminuria. We evaluated whether this approach would have an effect on the rates of death from any cause and from cardiovascular causes.

Methods: In the Steno-2 Study, we randomly assigned 160 patients with type 2 diabetes and persistent microalbuminuria to receive either intensive therapy or conventional therapy; the mean treatment period was 7.8 years. Patients were subsequently followed observationally for a mean of 5.5 years, until December 31, 2006. The primary end point at 13.3 years of follow-up was the time to death from any cause.

Results: Twenty-four patients in the intensive-therapy group died, as compared with 40 in the conventional-therapy group (hazard ratio, 0.54; 95% confidence interval [CI], 0.32 to 0.89; P=0.02). Intensive therapy was associated with a lower risk of death from cardiovascular causes (hazard ratio, 0.43; 95% CI, 0.19 to 0.94; P=0.04) and of cardiovascular events (hazard ratio, 0.41; 95% CI, 0.25 to 0.67; P<0.001). One patient in the intensive-therapy group had progression to end-stage renal disease, as compared with six patients in the conventional-therapy group (P=0.04). Fewer patients in the intensive-therapy group required retinal photocoagulation (relative risk, 0.45; 95% CI, 0.23 to 0.86; P=0.02). Few major side effects were reported.

Conclusions: In at-risk patients with type 2 diabetes, intensive intervention with multiple drug combinations and behavior modification had sustained beneficial effects with respect to vascular complications and on rates of death from any cause and from cardiovascular causes. (ClinicalTrials.gov number, NCT00320008.)

Publication types

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

MeSH terms

  • Aged
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Aspirin / therapeutic use
  • Behavior Therapy
  • Cardiovascular Diseases / epidemiology
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / prevention & control
  • Cause of Death
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / mortality
  • Diabetes Mellitus, Type 2 / therapy*
  • Diabetic Neuropathies / epidemiology
  • Drug Therapy, Combination
  • Follow-Up Studies
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Hypolipidemic Agents / therapeutic use
  • Kaplan-Meier Estimate
  • Middle Aged
  • Platelet Aggregation Inhibitors / therapeutic use
  • Risk Factors

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Platelet Aggregation Inhibitors
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00320008