Effects of Combination Lipid Therapy in Type 2 Diabetes Mellitus

N Engl J Med. 2010 Apr 29;362(17):1563-74. doi: 10.1056/NEJMoa1001282. Epub 2010 Mar 14.

Abstract

Background: We investigated whether combination therapy with a statin plus a fibrate, as compared with statin monotherapy, would reduce the risk of cardiovascular disease in patients with type 2 diabetes mellitus who were at high risk for cardiovascular disease.

Methods: We randomly assigned 5518 patients with type 2 diabetes who were being treated with open-label simvastatin to receive either masked fenofibrate or placebo. The primary outcome was the first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. The mean follow-up was 4.7 years.

Results: The annual rate of the primary outcome was 2.2% in the fenofibrate group and 2.4% in the placebo group (hazard ratio in the fenofibrate group, 0.92; 95% confidence interval [CI], 0.79 to 1.08; P=0.32). There were also no significant differences between the two study groups with respect to any secondary outcome. Annual rates of death were 1.5% in the fenofibrate group and 1.6% in the placebo group (hazard ratio, 0.91; 95% CI, 0.75 to 1.10; P=0.33). Prespecified subgroup analyses suggested heterogeneity in treatment effect according to sex, with a benefit for men and possible harm for women (P=0.01 for interaction), and a possible interaction according to lipid subgroup, with a possible benefit for patients with both a high baseline triglyceride level and a low baseline level of high-density lipoprotein cholesterol (P=0.057 for interaction).

Conclusions: The combination of fenofibrate and simvastatin did not reduce the rate of fatal cardiovascular events, nonfatal myocardial infarction, or nonfatal stroke, as compared with simvastatin alone. These results do not support the routine use of combination therapy with fenofibrate and simvastatin to reduce cardiovascular risk in the majority of high-risk patients with type 2 diabetes. (ClinicalTrials.gov number, NCT00000620.)

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aged
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control*
  • Cholesterol / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Fenofibrate / adverse effects
  • Fenofibrate / therapeutic use*
  • Follow-Up Studies
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Hypolipidemic Agents / adverse effects
  • Hypolipidemic Agents / therapeutic use*
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / prevention & control
  • Proportional Hazards Models
  • Sex Factors
  • Simvastatin / therapeutic use*
  • Stroke / epidemiology
  • Stroke / prevention & control
  • Treatment Failure
  • Triglycerides / blood

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Hypolipidemic Agents
  • Triglycerides
  • Cholesterol
  • Simvastatin
  • Fenofibrate

Associated data

  • ClinicalTrials.gov/NCT00000620