Document Detail

Effect of various diuretic treatments on rosiglitazone-induced fluid retention.
MedLine Citation:
PMID:  17093067     Owner:  NLM     Status:  MEDLINE    
The efficacy of diuretics in the management of rosiglitazone (RSG)-induced fluid retention was evaluated in a multicenter, randomized, open-label, parallel-group, proof-of-concept study. Of 381 patients who had type 2 diabetes and were on treatment with sulfonylurea or sulfonylurea plus metformin, 260 (63% male, 37% female) showed evidence of volume expansion as defined by an absolute reduction in hematocrit (Hct) of > or =0.5% after 12 wk of rosiglitazone 4 mg twice daily. They were randomly assigned to five treatments for 7 d: (1) Continuation of RSG (RSG-C), (2) RSG + furosemide (RSG+FRUS), (3) RSG + hydrochlorothiazide (RSG+HCTZ), (4) RSG + spironolactone (RSG+SPIRO), and (5) discontinuation of RSG. The primary end point was change in Hct at day 7 of diuretic treatment phase, powered to compare each diuretic group and the RSG discontinuation with the control group of RSG-C, with adjustments for multiple testing. After 12 wk on RSG, Hct fell by mean of 2.92% (95% confidence interval [CI] -3.10 to -2.63%; P < 0.001) and extracellular fluid volume increased by 0.62 L/1.73 m(2) (95% CI 0.26 to 0.90 L/1.73 m(2); P < 0.001). After treatment, the RSG+SPIRO group only showed a mean increase in Hct of 0.24%. The estimated mean difference in Hct reduction was significant: 1.14% (95% CI 0.29 to 1.98%) for RSG+SPIRO (P = 0.004) and 0.87% (95% CI 0.03 to 1.71%) for RSG+HCTZ (P = 0.041) only. In additional analyses of between-diuretic treatment effects SPIRO induced a greater Hct rescue at 0.88% (95% CI -0.12 to 1.87%; P = 0.095) and extracellular fluid volume reduction of -0.75 L/1.73 m(2) (95% CI -1.52 to 0.03 L/1.73 m(2); P = 0.06) compared with FRUS, suggesting superiority in the management of RSG-associated fluid retention. There were no significant differences between SPIRO and HCTZ. These findings are consistent with peroxisome proliferator-activated receptor-gamma agonist activation of the epithelial sodium channel in the distal collecting duct, a site of action of SPIRO and a potential target for thiazide diuretics.
Janaka Karalliedde; Robin Buckingham; Margaret Starkie; Daniel Lorand; Murray Stewart; Giancarlo Viberti;
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Publication Detail:
Type:  Comparative Study; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2006-11-08
Journal Detail:
Title:  Journal of the American Society of Nephrology : JASN     Volume:  17     ISSN:  1046-6673     ISO Abbreviation:  J. Am. Soc. Nephrol.     Publication Date:  2006 Dec 
Date Detail:
Created Date:  2006-11-28     Completed Date:  2007-02-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9013836     Medline TA:  J Am Soc Nephrol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3482-90     Citation Subset:  IM    
Unit for Metabolic Medicine, Department of Diabetes and Endocrinology, Cardiovascular Division, King's College London School of Medicine, Guy's Hospital, King's College London, London, London SE1 9RT, UK.
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MeSH Terms
Aged, 80 and over
Diabetes Mellitus, Type 2 / drug therapy*
Diuretics / therapeutic use*
Drug Therapy, Combination
Edema / chemically induced,  drug therapy*
Extracellular Fluid / drug effects
Furosemide / therapeutic use
Hydrochlorothiazide / therapeutic use
Hypoglycemic Agents / adverse effects*,  therapeutic use
Middle Aged
Plasma Volume / drug effects*
Spironolactone / therapeutic use
Sulfonylurea Compounds / therapeutic use
Thiazolidinediones / adverse effects*,  therapeutic use
Reg. No./Substance:
0/Diuretics; 0/Hypoglycemic Agents; 0/Sulfonylurea Compounds; 0/Thiazolidinediones; 122320-73-4/rosiglitazone; 52-01-7/Spironolactone; 54-31-9/Furosemide; 58-93-5/Hydrochlorothiazide

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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