title: Effect of spironolactone and amiloride on thiazolidinedione-induced fluid retention in South Indian patients with type 2 diabetes.
abstract: OBJECTIVE
  Thiazolidinediones (pioglitazone and rosiglitazone) induce renal epithelial sodium channel (ENaC)-mediated sodium reabsorption, resulting in plasma volume (PV) expansion. Incidence and long-term management of fluid retention induced by thiazolidinediones remain unclear.
  
  
  METHODS
  In a 4-week run-in period, rosiglitazone, 4 mg twice daily, was added to a background anti-diabetic therapy in 260 South Indian patients with type 2 diabetes mellitus. Patients with PV expansion (absolute reduction in hematocrit in run-in, ≥1.5 percentage points) entered a randomized, placebo-controlled study to evaluate effects of amiloride and spironolactone on attenuating rosiglitazone-induced fluid retention. Primary endpoint was change in hematocrit in each diuretic group versus placebo (control group).
  
  
  RESULTS
  Of the 260 patients, 70% (n=180) had PV expansion. These 180 patients (70% male; mean age, 47.8 years [range, 30-80 years]) were randomly assigned to rosiglitazone, 4 mg twice daily, plus spironolactone, 50 mg once daily; rosiglitazone, 4 mg twice daily, plus amiloride, 10 mg once daily; or rosiglitazone, 4 mg twice daily, plus placebo for 24 weeks. Hematocrit continued to decrease significantly in control and spironolactone groups (mean absolute change, -1.2 [P=0.01] and -0.7 [P=0.02] percentage points, respectively), suggesting continued PV expansion. No change occurred with amiloride (mean change, 0.0 percentage points). Amiloride, but not spironolactone, was superior to control (mean hematocrit difference [95% confidence interval] relative to control, 1.27 [0.21-2.55] and 0.49 [-0.79-1.77] percentage points [P=0.04 and P=0.61], respectively).
  
  
  CONCLUSIONS
  Prevalence of rosiglitazone-induced fluid retention in South Indian patients with type 2 diabetes is high. Amiloride, a direct ENaC blocker, but not spironolactone, prevented protracted fluid retention in these patients.
authors.affiliation: Department of Diabetes, M.V. Hospital for Diabetes and Prof M. Viswanathan Diabetes Research Centre, Chennai, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Viswanathan
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
authors.forename: Poongothai
authors.initials: P
authors.lastname: Subramani
authors.forename: Nandakumar
authors.initials: N
authors.lastname: Parthasarathy
authors.forename: Gayathri
authors.initials: G
authors.lastname: Subramaniyam
authors.forename: Deepa
authors.initials: D
authors.lastname: Manoharan
authors.forename: Chandru
authors.initials: C
authors.lastname: Sundaramoorthy
authors.forename: Luigi
authors.initials: L
authors.lastname: Gnudi
authors.forename: Janaka
authors.initials: J
authors.lastname: Karalliedde
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Viberti
mesh_terms: D000328:Adult; D000368:Aged; D000584:Amiloride / Q000627:therapeutic use*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004232:Diuretics / Q000627:therapeutic use*; D004487:Edema / Q000139:chemically induced* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D013148:Spironolactone / Q000627:therapeutic use*; D045162:Thiazolidinediones / Q000009:adverse effects*
chemical_list: D004232:Diuretics; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D013148:Spironolactone; D000584:Amiloride