title: Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease.
abstract: BACKGROUND
  Recent studies have shown that type 2 diabetes is preventable by both lifestyle interventions and medications that influence primary glucose metabolism. Whether pharmacological interventions that influence primary lipid metabolism can also delay development of type 2 diabetes is unknown. The goal of this study was to evaluate the effect of the peroxisome proliferator-activated receptor ligand bezafibrate on the progression of impaired fasting glucose phase to type 2 diabetes in patients with coronary artery disease over a 6.2-year follow-up period.
  
  
  RESULTS
  The study sample comprised 303 nondiabetic patients 42 to 74 years of age with a fasting blood glucose level of 110 to 125 mg/dL (6.1 to 6.9 mmol/L). The patients received either 400 mg bezafibrate retard (156 patients) or placebo (147 patients) once a day. No patients were using statins, and use of ACE inhibitors, which also reduce diabetes incidence, was relatively low. During follow-up, development of new-onset diabetes was recorded in 146 patients: in 80 (54.4%) from the placebo group and 66 (42.3%) from the bezafibrate group (P=0.04). The mean time until onset of new diabetes was significantly delayed in patients on bezafibrate compared with patients on placebo: 4.6+/-2.3 versus 3.8+/-2.6 years (P=0.004). Multivariate analysis identified bezafibrate treatment as an independent predictor of reduced risk of new diabetes development (hazard ratio, 0.70; 95% CI, 0.49 to 0.99). Other significant variables associated with future overt type 2 diabetes in patients with impaired fasting glucose were total cholesterol level (hazard ratio, 1.22; 95% CI 1.0 to 1.51) and body mass index (hazard ratio, 1.10; 95% CI, 1.05 to 1.16).
  
  
  CONCLUSIONS
  Bezafibrate reduces the incidence and delays the onset of type 2 diabetes in patients with impaired fasting glucose. Whether the combination of bezafibrate with other recommended drugs for secondary prevention (statins and ACE inhibitors) would be as efficacious as suggested by our results remains to be determined.
authors.affiliation: Cardiac Rehabilitation Institute, Chaim Sheba Medical Center, Tel-Hashomer, 52621 Israel. altenen@post.tau.ac.il
authors.forename: Alexander
authors.initials: A
authors.lastname: Tenenbaum
authors.forename: Michael
authors.initials: M
authors.lastname: Motro
authors.forename: Enrique Z
authors.initials: EZ
authors.lastname: Fisman
authors.forename: Ehud
authors.initials: E
authors.lastname: Schwammenthal
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Adler
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
authors.forename: Jonathan
authors.initials: J
authors.lastname: Leor
authors.forename: Valentina
authors.initials: V
authors.lastname: Boyko
authors.forename: Lori
authors.initials: L
authors.lastname: Mandelzweig
authors.forename: Solomon
authors.initials: S
authors.lastname: Behar
mesh_terms: D000368:Aged; D001629:Bezafibrate / Q000494:pharmacology / Q000627:therapeutic use*; D001786:Blood Glucose / Q000032:analysis; D002784:Cholesterol / Q000097:blood; D015897:Comorbidity; D003327:Coronary Disease / Q000097:blood / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000097:blood; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D014157:Transcription Factors / Q000819:agonists*
chemical_list: D001786:Blood Glucose; D000960:Hypolipidemic Agents; D007328:Insulin; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D002784:Cholesterol; D001629:Bezafibrate