A pilot randomized controlled trial of renal protection with pioglitazone in diabetic nephropathy.
BACKGROUND
Diabetic nephropathy progresses relentlessly to end-stage renal disease (ESRD). Animal experiments have found that peroxisome proliferator activated receptor-gamma (PPAR-gamma)-based therapy can have a glucose independent effect on renal protection. We hypothesized that PPAR-gamma-based antidiabetic therapy would result in greater reduction in proteinuria compared to sulfonylurea-based therapy.


METHODS
In 44 patients with overt diabetic nephropathy, an open-label, blinded end point trial was conducted in which subjects were randomized to either pioglitazone or glipizide to achieve similar glucose control. Proteinuria was assessed by two collections of 24-hour urine samples each month for 4 months.


RESULTS
The glipizide group had an adjusted mean increase in proteinuria of 6.1% (95% CI -11.7%, 23.8%), whereas the pioglitazone group had a reduction of 7.2% (95% CI -24.9%, 10.6%). The adjusted reduction with pioglitazone of 13.2% (95% CI -38.4%, 11.9%) was not statistically significant (P= 0.294). Baseline proteinuria, diastolic ambulatory blood pressure, and serum albumin concentration were independent predictors of reduction in proteinuria. The frequency and patterns of adverse events were similar in the two groups.


CONCLUSIONS
In patients with advanced diabetic nephropathy, we found no reduction in proteinuria over 4 months. These data are useful to design larger studies with longer duration of follow-up to demonstrate renal protection of PPAR-gamma agonists.
Agarwal
Rajiv
R
Division of Nephrology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA. ragarwal@iupui.edu
Saha
Chandan
C
Battiwala
Meher
M
Vasavada
Nina
N
Curley
Timothy
T
Chase
Shawn D
SD
Sachs
Nadine
N
Semret
Merfake H
MH
D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000517:prevention & control*; D005260:Female; D005913:Glipizide / Q000008:administration & dosage; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone; D005913:Glipizide