Objective: To evaluate the efficacy and safety of combination therapy with candesartan cilexetil (CC) and pioglitazone hydrochloride (PIO) in patients with hypertension and type 2 diabetes mellitus.
Methods: A 12-week, double-blind, randomized, parallel-group study in patients with mild-to-moderate essential hypertension and type 2 diabetes mellitus was followed by a 40-week, single-blind study. Patients (N = 377) were randomized to treatment with CC 8 mg/PIO 30 mg (n = 62), CC 8 mg/PIO 15 mg (n = 63), CC 4 mg/PIO 30 mg (n = 63), CC 4 mg/PIO 15 mg (n = 63), CC 8 mg/PIO 0 mg (n = 63), or CC 0 mg/PIO 30 mg (n = 63). Primary efficacy measures were changes in diastolic blood pressure (DBP) and HbA(1C) at Week 12.
Results: CC/PIO combination therapy improved blood pressure (BP)/glycemic control for 52 weeks. At the end of 12-week treatment period, DBP decreased to a significantly greater extent in the 8/30 + 8/15 + 8/0 (combined CC 8 mg) group (-10.5 mmHg, p < 0.0001) and the 4/30 + 4/15 (combined CC 4 mg) group (-9.1 mmHg, p = 0.0022) than in the 0/30 (CC 0 mg) group (-5.3 mmHg). HbA(1C) significantly decreased in the 8/30 + 4/30 + 0/30 (combined PIO 30 mg) group (-0.35%, p < 0.0001) and the 8/15 + 4/15 (combined PIO 15 mg) group (-0.15%, p < 0.0001) compared with the 8/0 (PIO 0 mg) group (0.35%). Urinary albumin excretion reduction seen with the 0/30 and the 8/0 groups was significantly enhanced by CC/PIO combination. Clinical significance of this renoprotective effect of CC/PIO combination therapy needs to be studied further. Prolonged combined use of CC/PIO did not increase adverse events. Drug-related adverse events were similar to those during clinical use of CC and PIO.
Conclusion: CC/PIO combination therapy improved BP/glycemic control and was well tolerated for 52 weeks. Thus, CC/PIO combination therapy is useful in patients with hypertension and type 2 diabetes mellitus.