Initial Combination Therapy With Alogliptin and Pioglitazone in Diabetes
Initial Combination Therapy With Alogliptin and Pioglitazone in Diabetes
Objective To assess the efficacy and tolerability of alogliptin plus pioglitazone for initial combination therapy in drug-naĂ¯ve type 2 diabetic patients.
Research Design and Methods This 26-week, double-blind, parallel-group study randomized 655 patients with inadequately controlled type 2 diabetes to four arms: 25 mg alogliptin (A25) q.d. monotherapy, 30 mg pioglitazone (P30) q.d. monotherapy, or 12.5 (A12.5) or 25 mg alogliptin q.d. plus pioglitazone (P30) q.d. combination therapy. Primary efficacy was A1C change from baseline with the high-dose combination (A25 + P30) versus each monotherapy.
Results Combination therapy with A25 + P30 resulted in greater reductions in A1C (−1.7 ± 0.1% from an 8.8% mean baseline) vs. A25 (−1.0 ± 0.1%, P < 0.001) or P30 (−1.2 ± 0.1%, P < 0.001) and in fasting plasma glucose (−2.8 ± 0.2 mmol/l) vs. A25 (−1.4 ± 0.2 mmol/l, P < 0.001) or P30 (−2.1 ± 0.2 mmol/l, P = 0.006). The A25 + P30 safety profile was consistent with those of its component monotherapies.
Conclusions Alogliptin plus pioglitazone combination treatment appears to be an efficacious initial therapeutic option for type 2 diabetes.
Because the pathogenesis of type 2 diabetes involves defects in both insulin secretion and insulin action, simplified, well-tolerated, and durably effective combination therapies are being considered as potential standard initial treatment strategies to increase the likelihood of achieving sustained glycemic targets. Two drug classes that have complementary modes of action and may prove efficacious in combination are thiazolidinediones (TZDs), which are insulin sensitizers that increase peripheral glucose uptake, and dipeptidyl peptidase (DPP)-4 inhibitors, which augment pancreatic insulin secretion and also reduce hepatic glucose output through a suppressive effect on pancreatic glucagon secretion. This phase 3 study was conducted in drug-naĂ¯ve patients with type 2 diabetes inadequately controlled with diet and exercise to evaluate the effects of initial combination therapy with the DPP-4 inhibitor alogliptin and the TZD pioglitazone versus either component used alone.
Abstract and Introduction
Abstract
Objective To assess the efficacy and tolerability of alogliptin plus pioglitazone for initial combination therapy in drug-naĂ¯ve type 2 diabetic patients.
Research Design and Methods This 26-week, double-blind, parallel-group study randomized 655 patients with inadequately controlled type 2 diabetes to four arms: 25 mg alogliptin (A25) q.d. monotherapy, 30 mg pioglitazone (P30) q.d. monotherapy, or 12.5 (A12.5) or 25 mg alogliptin q.d. plus pioglitazone (P30) q.d. combination therapy. Primary efficacy was A1C change from baseline with the high-dose combination (A25 + P30) versus each monotherapy.
Results Combination therapy with A25 + P30 resulted in greater reductions in A1C (−1.7 ± 0.1% from an 8.8% mean baseline) vs. A25 (−1.0 ± 0.1%, P < 0.001) or P30 (−1.2 ± 0.1%, P < 0.001) and in fasting plasma glucose (−2.8 ± 0.2 mmol/l) vs. A25 (−1.4 ± 0.2 mmol/l, P < 0.001) or P30 (−2.1 ± 0.2 mmol/l, P = 0.006). The A25 + P30 safety profile was consistent with those of its component monotherapies.
Conclusions Alogliptin plus pioglitazone combination treatment appears to be an efficacious initial therapeutic option for type 2 diabetes.
Introduction
Because the pathogenesis of type 2 diabetes involves defects in both insulin secretion and insulin action, simplified, well-tolerated, and durably effective combination therapies are being considered as potential standard initial treatment strategies to increase the likelihood of achieving sustained glycemic targets. Two drug classes that have complementary modes of action and may prove efficacious in combination are thiazolidinediones (TZDs), which are insulin sensitizers that increase peripheral glucose uptake, and dipeptidyl peptidase (DPP)-4 inhibitors, which augment pancreatic insulin secretion and also reduce hepatic glucose output through a suppressive effect on pancreatic glucagon secretion. This phase 3 study was conducted in drug-naĂ¯ve patients with type 2 diabetes inadequately controlled with diet and exercise to evaluate the effects of initial combination therapy with the DPP-4 inhibitor alogliptin and the TZD pioglitazone versus either component used alone.
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