Effects of the peroxisome proliferator-activated receptor (PPAR)-gamma agonist pioglitazone on renal and hormonal responses to salt in diabetic and hypertensive individuals

Diabetologia. 2010 Aug;53(8):1568-75. doi: 10.1007/s00125-010-1756-2. Epub 2010 Apr 23.


Aims/hypothesis: Glitazones are powerful insulin sensitisers prescribed for the treatment of type 2 diabetes. Their use is, however, associated with fluid retention and an increased risk of congestive heart failure. We previously demonstrated that pioglitazone increases proximal sodium reabsorption in healthy volunteers. This study examines the effects of pioglitazone on renal sodium handling in individuals prone to insulin resistance, i.e. those with diabetes and/or hypertension.

Methods: In this double-blind randomised placebo-controlled four-way crossover study, we examined the effects of pioglitazone (45 mg daily during 6 weeks) or placebo on renal, systemic and hormonal responses to changes in sodium intake in 16 individuals, eight with type 2 diabetes and eight with hypertension.

Results: Pioglitazone was associated with a rapid increase in body weight and an increase in diurnal proximal sodium reabsorption, without any change in renal haemodynamics or in the modulation of the renin-angiotensin aldosterone system to changes in salt intake. A compensatory increase in brain natriuretic peptide levels was observed. In spite of sodium retention, pioglitazone dissociated the blood-pressure response to salt and abolished salt sensitivity in salt-sensitive individuals.

Conclusions/interpretation: Pioglitazone increases diurnal proximal sodium retention in diabetic and hypertensive individuals. These effects cause fluid retention and may contribute to the increased incidence of congestive heart failure with glitazones.

Trial registration: ClinicalTrial.gov NCT01090752

Funding: Hypertension Research Foundation Lausanne.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Blood Pressure / drug effects
  • Body Weight / drug effects
  • Cross-Over Studies
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Double-Blind Method
  • Female
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypoglycemic Agents / therapeutic use
  • Insulin Resistance
  • Male
  • Metformin / therapeutic use
  • Natriuretic Peptide, Brain / blood
  • Pioglitazone
  • Sodium, Dietary / metabolism*
  • Thiazolidinediones / therapeutic use*


  • Hypoglycemic Agents
  • Sodium, Dietary
  • Thiazolidinediones
  • Natriuretic Peptide, Brain
  • Metformin
  • Pioglitazone

Associated data

  • ClinicalTrials.gov/NCT01090752