title: Preventing microalbuminuria in type 2 diabetes.
abstract: BACKGROUND
  The multicenter double-blind, randomized Bergamo Nephrologic Diabetes Complications Trial (BENEDICT) was designed to assess whether angiotensin-converting-enzyme inhibitors and non-dihydropyridine calcium-channel blockers, alone or in combination, prevent microalbuminuria in subjects with hypertension, type 2 diabetes mellitus, and normal urinary albumin excretion.
  
  
  METHODS
  We studied 1204 subjects, who were randomly assigned to receive at least three years of treatment with trandolapril (at a dose of 2 mg per day) plus verapamil (sustained-release formulation, 180 mg per day), trandolapril alone (2 mg per day), verapamil alone (sustained-release formulation, 240 mg per day), or placebo. The target blood pressure was 120/80 mm Hg. The primary end point was the development of persistent microalbuminuria (overnight albumin excretion, > or =20 microg per minute at two consecutive visits).
  
  
  RESULTS
  The primary outcome was reached in 5.7 percent of the subjects receiving trandolapril plus verapamil, 6.0 percent of the subjects receiving trandolapril, 11.9 percent of the subjects receiving verapamil, and 10.0 percent of control subjects receiving placebo. The estimated acceleration factor (which quantifies the effect of one treatment relative to another in accelerating or slowing disease progression) adjusted for predefined baseline characteristics was 0.39 for the comparison between verapamil plus trandolapril and placebo (P=0.01), 0.47 for the comparison between trandolapril and placebo (P=0.01), and 0.83 for the comparison between verapamil and placebo (P=0.54). Trandolapril plus verapamil and trandolapril alone delayed the onset of microalbuminuria by factors of 2.6 and 2.1, respectively. Serious adverse events were similar in all treatment groups.
  
  
  CONCLUSIONS
  In subjects with type 2 diabetes and hypertension but with normoalbuminuria, the use of trandolapril plus verapamil and trandolapril alone decreased the incidence of microalbuminuria to a similar extent. The effect of verapamil alone was similar to that of placebo.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases, Aldo e Cele Daccò, Villa Camozzi, Ranica, Bergamo, Italy. manuelap@marionegri.it
authors.forename: Piero
authors.initials: P
authors.lastname: Ruggenenti
authors.forename: Anna
authors.initials: A
authors.lastname: Fassi
authors.forename: Anelja Parvanova
authors.initials: AP
authors.lastname: Ilieva
authors.forename: Simona
authors.initials: S
authors.lastname: Bruno
authors.forename: Ilian Petrov
authors.initials: IP
authors.lastname: Iliev
authors.forename: Varusca
authors.initials: V
authors.lastname: Brusegan
authors.forename: Nadia
authors.initials: N
authors.lastname: Rubis
authors.forename: Giulia
authors.initials: G
authors.lastname: Gherardi
authors.forename: Federica
authors.initials: F
authors.lastname: Arnoldi
authors.forename: Maria
authors.initials: M
authors.lastname: Ganeva
authors.forename: Bogdan
authors.initials: B
authors.lastname: Ene-Iordache
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
authors.forename: Annalisa
authors.initials: A
authors.lastname: Perna
authors.forename: Antonio
authors.initials: A
authors.lastname: Bossi
authors.forename: Roberto
authors.initials: R
authors.lastname: Trevisan
authors.forename: Alessandro R
authors.initials: AR
authors.lastname: Dodesini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000517:prevention & control*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000188:drug therapy; D018450:Disease Progression; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D016896:Treatment Outcome; D014700:Verapamil / Q000627:therapeutic use*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007211:Indoles; C052035:trandolapril; D014700:Verapamil