A randomized trial of therapies for type 2 diabetes and coronary artery disease.
BACKGROUND
Optimal treatment for patients with both type 2 diabetes mellitus and stable ischemic heart disease has not been established.


METHODS
We randomly assigned 2368 patients with both type 2 diabetes and heart disease to undergo either prompt revascularization with intensive medical therapy or intensive medical therapy alone and to undergo either insulin-sensitization or insulin-provision therapy. Primary end points were the rate of death and a composite of death, myocardial infarction, or stroke (major cardiovascular events). Randomization was stratified according to the choice of percutaneous coronary intervention (PCI) or coronary-artery bypass grafting (CABG) as the more appropriate intervention.


RESULTS
At 5 years, rates of survival did not differ significantly between the revascularization group (88.3%) and the medical-therapy group (87.8%, P=0.97) or between the insulin-sensitization group (88.2%) and the insulin-provision group (87.9%, P=0.89). The rates of freedom from major cardiovascular events also did not differ significantly among the groups: 77.2% in the revascularization group and 75.9% in the medical-treatment group (P=0.70) and 77.7% in the insulin-sensitization group and 75.4% in the insulin-provision group (P=0.13). In the PCI stratum, there was no significant difference in primary end points between the revascularization group and the medical-therapy group. In the CABG stratum, the rate of major cardiovascular events was significantly lower in the revascularization group (22.4%) than in the medical-therapy group (30.5%, P=0.01; P=0.002 for interaction between stratum and study group). Adverse events and serious adverse events were generally similar among the groups, although severe hypoglycemia was more frequent in the insulin-provision group (9.2%) than in the insulin-sensitization group (5.9%, P=0.003).


CONCLUSIONS
Overall, there was no significant difference in the rates of death and major cardiovascular events between patients undergoing prompt revascularization and those undergoing medical therapy or between strategies of insulin sensitization and insulin provision. (ClinicalTrials.gov number, NCT00006305.)
Frye
Robert L
RL
August
Phyllis
P
Brooks
Maria Mori
MM
Hardison
Regina M
RM
Kelsey
Sheryl F
SF
MacGregor
Joan M
JM
Orchard
Trevor J
TJ
Chaitman
Bernard R
BR
Genuth
Saul M
SM
Goldberg
Suzanne H
SH
Hlatky
Mark A
MA
Jones
Teresa L Z
TL
Molitch
Mark E
ME
Nesto
Richard W
RW
Sako
Edward Y
EY
Sobel
Burton E
BE
D015906:Angioplasty, Balloon, Coronary; D003131:Combined Modality Therapy; D017023:Coronary Angiography; D001026:Coronary Artery Bypass; D003327:Coronary Disease / Q000150:complications / Q000601:surgery / Q000628:therapy*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006442:Glycated Hemoglobin; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000009:adverse effects / Q000627:therapeutic use*; D053208:Kaplan-Meier Estimate; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology / Q000517:prevention & control; D020521:Stroke / Q000453:epidemiology / Q000517:prevention & control; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use
D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008687:Metformin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C089946:2,4-thiazolidinedione