Effects of combination lipid therapy in type 2 diabetes mellitus.
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.)
Ginsberg
Henry N
HN
Elam
Marshall B
MB
Lovato
Laura C
LC
Crouse
John R
JR
Leiter
Lawrence A
LA
Linz
Peter
P
Friedewald
William T
WT
Buse
John B
JB
Gerstein
Hertzel C
HC
Probstfield
Jeffrey
J
Grimm
Richard H
RH
Ismail-Beigi
Faramarz
F
Bigger
J Thomas
JT
Goff
David C
DC
Cushman
William C
WC
Simons-Morton
Denise G
DG
Byington
Robert P
RP
D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D005260:Female; D011345:Fenofibrate / Q000009:adverse effects / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D000960:Hypolipidemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D016016:Proportional Hazards Models; D012737:Sex Factors; D019821:Simvastatin / Q000627:therapeutic use*; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D017211:Treatment Failure; D014280:Triglycerides / Q000097:blood
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D000960:Hypolipidemic Agents; D014280:Triglycerides; D002784:Cholesterol; D019821:Simvastatin; D011345:Fenofibrate