By Brian Hoyle
MONTREAL -- October 23, 2009 -- Pioglitazone is therapeutically beneficial for hypertensive patients with type 2 diabetes, compared with metformin, reducing urinary albumin excretion when supplied as an adjunct to renin-angiotensin system (RAS) inhibitors including angiotensin II receptor blockers (ARBs) or angiotensin converting enzyme-1 (ACE-1).
This was the conclusion of the multi-institute Asahikawa Prospective Pioglitazone in Microalbuminuria Effect (A-PRIME) study presented here October 20 at the 20th World Diabetes Congress of the International Diabetes Federation (IDF).
Akizuki Morikawa MD, Asahikawa Red Cross Hospital, Asahikawa, Japan, and colleagues conducted an open-label, randomised study in 70 patients with type 2 diabetes who had been diagnosed with hypertension and microalbuminuria (urinary albumin/creatinine ratio [UACR] >=30 mg/g Cr to <300 mg/g Cr).
All patients who had received an ARB or ACE for at least 12 weeks (during which time 2 exited the study), were randomised to receive pioglitazone 15 or 30 mg/day (n = 32) or metformin 500 or 750 mg/day (n = 31) for 52 weeks. They continued to receive the particular ARB or ACE-1.
Of those treated with pioglitazone, the ARBs included candesartan 4 to 12 mg (n = 10), valsartan 40 to 160 mg (n = 7), telmisartan 20 to 40 mg (n = 9), olmesartan 10 to 40 mg (n = 1), and losartan 25 to 50 mg (n = 1). Four participants received ACE-1.
Of those treated with metformin, the breakdown of the use of the same concentrations of ARBs were candesartan (n = 11), valsartan (n = 11), telmisartan (n = 2), olmesartan (n = 3), and losartan (n=1). Three participants received ACE-1.
During the year-long study, UACR, glycated haemoglobin (Hb A1C), fasting blood glucose, blood pressure, low- and high-density cholesterol, triglyceride, and body weight were measured every 2 weeks.
The UACR decreased significantly (P < .05) in those receiving pioglitazone (-16.6%; 148.0 mg/g Cr at week 0, 123.4 mg/g Cr at week 52) and increased in the metformin group (53.7%; 114.5 mg/g Cr at week 0, 175.9 mg/g Cr at week 52). Hb A1C decreased in both groups; the decline was larger but not significant in the pioglitazone group (0.8%) compared to the metformin group (0.3%).
Decreases were also evident in mean systolic blood pressure (3.3 and 5.6 mm Hg in the pioglitazone and metformin groups, respectively), but the difference was not significant. No significant differences were evident between the treatment groups for the other measured parameters.
Adverse events occurred in 3 of those receiving pioglitazone (1 unstable angina, 2 peripheral oedema; 8.3%), and in 2 of those receiving metformin (1 headache, 1 sudden death, 6.3%). The difference was not significant.
As an add-on to RAS inhibitor therapy, pioglitazone is more beneficial than metformin in terms of reducing urinary albumin excretion, concluded the researchers. Larger studies involving more patients will be needed to substantiate the findings.
Funding for this study was provided by Asahikawa Red Cross Hospital.
[Presentation title: Pioglitazone Reduces Urinary Albumin Excretion in RAS Inhibitor-Treated Type 2 Diabetic Patients With Hypertension and Microalbuminuria: A Prospective, Randomized Study. Abstract D-0819]
E-Mail this DGDispatch to a colleague
