Candesartan and Pioglitazone Demonstrate Anti-inflammatory Properties

The use of the ARB, candesartan, and the oral anti-diabetic drug, pioglitazone, not only improved blood pressure and HbA1c levels, but serum levels of inflammatory proteins were reduced in type 2 diabetes patients….

A recent study out of Cardiovascular Diabetology looked at the potential benefits of the combination of candesartan and pioglitazone in type 2 diabetic patients with hypertension. The aim of this preliminary report was to better understand the potential anti-inflammatory effects of these two medications in a certain patient population.

The authors of this research study chose pioglitazone as the oral anti-diabetic drug due to the reduction in cardiovascular events and stroke based on the PROactive Study. The reductions of cardiovascular events with the use of angiotensin receptor blockers (ARBs) are already well known. The clinical significance of using the combination of these two medications in regards to their anti-inflammatory properties is yet to be understood.

The study enrolled 41 patients diagnosed with type 2 diabetes and concomitant hypertension defined by a blood pressure ≥130/80. Patients diagnosed with secondary hypertension, liver disease, impaired kidney function or unstable cardiovascular conditions were excluded. The patients received concomitant administration of 12mg daily of candesartan and 15mg of pioglitazone for 6 months. Patients were evaluated for inflammatory parameters based off serum levels of high-molecular-weight adiponectin (HMW-ADN), plasminogen activator inhibitor-1 (PAI-1), highly sensitive C-reactive protein (Hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), and urinary-8-hydroxydeoxyguanosine (U-8-OHdG). Further analysis was conducted to determine the association of a reduction in blood pressure and HbA1c to decreased inflammatory proteins.

The authors recorded the results of 39 patients who completed the study. There was a significant reduction from baseline data in the average fasting blood glucose and HbA1c after 6 months of treatment. Furthermore, the authors reported a significant reduction in the average systolic blood pressure. In regards to the inflammatory parameters, a significant reduction of adiponectin (HMW-ADN) and plasminogen activator inhibitor-1 (PAI-1) was seen in all patients. Serum levels of highly sensitive C-reactive protein (Hs-CRP), vascular cell adhesion molecule-1 (VCAM-1), and urinary-8-hydroxydeoxyguanosine (U-8-OHdG) did not differ significantly from baseline.

The authors observed a positive correlation in the reduction of HbA1c and with the reduction of inflammatory proteins HMW-AND and PAI-1. However what was not determined was whether improved glucose control reduced inflammation or vice versa. The authors did not observe a correlation between a change in blood pressure and serum inflammatory levels.

The small study sample and study design are limitations in this preliminary pilot study. Larger scale randomized clinical trials are needed to validate the presented results. However the authors concluded, "The co-administration of candesartan with pioglitazone could be an effective therapeutic strategy for treating hypertensive patients with type 2 diabetes."

Hirofumi Suzuki, Masaya Sakamoto, Takeshi Hayashi, et al. "Effects of co-administration of candesartan with pioglitazone on inflammatory parameters in hypertensive patients with type 2 diabetes mellitus: a preliminary report." Cardiovascular Diabetology 2013, 12:71 doi:10.1186/1475-2840-12-71