Objective: Type 2 diabetes mellitus (T2DM) management requires continuous treatment intensification due to progressive decline in ?-cell function in insulin resistant individuals. Initial combination therapy of a dipeptidyl peptidase (DPP)-4 inhibitor with a thiazolidinedione (TZD) may be rational. We assessed the effects of the DPP4 inhibitor alogliptin (ALO) combined with the TZD pioglitazone (PIO), vs ALO monotherapy or placebo (PBO), on ?-cell function and glycemic control in T2DM. Material and methods: A 16-week, two-center, randomized, double-blind, PBO-controlled, parallel-arm intervention study in 71 patients with well-controlled T2DM (age 59.1 ± 6.3 years; A1C 6.7 ± 0.1%) treated with metformin, sulfonylurea, orglinide monotherapy was conducted. Patients were treated with combined ALO 25 mg and PIO 30 mg daily or ALO 25 mg daily monotherapy or PBO. Main outcome measures included change in A1C and fasting plasma glucose (FPG) from baseline to week 16. In addition, change in ?-cell function parameters obtained from standardized meal tests at baseline and at week 16 was measured. Results: ALO/PIO and ALO decreased A1C from baseline by 0.9 ± 0.1 and 0.4 ± 0.2% respectively (both P<0.001 vs PBO). FPG was decreased to a greater extent by ALO/PIO compared with ALO monotherapy (P<0.01). ALO/PIO treatment improved ?-cell glucose sensitivity (vs PBO; P<0.001) and fasting secretory tone (vs PBO; P=0.001), while ALO monotherapy did not change ?-cell function parameters. All treatments were well tolerated. Conclusion: Short-term treatment with ALO/PIO or ALO improved glycemic control in well-controlled T2DM patients, but only combined ALO/PIO improved ?-cell function. These data support that initial combination therapy with a DPP4 inhibitor and TZD to address multiple core defects in T2DM may be a sensible approach. © 2014 European Society of Endocrinology Printed in Great Britain.
The effect of alogliptin and pioglitazone combination therapy on various aspects of ?-cell function in patients with recent-onset type 2 diabetes
Mari A;Tura A;
2014
Abstract
Objective: Type 2 diabetes mellitus (T2DM) management requires continuous treatment intensification due to progressive decline in ?-cell function in insulin resistant individuals. Initial combination therapy of a dipeptidyl peptidase (DPP)-4 inhibitor with a thiazolidinedione (TZD) may be rational. We assessed the effects of the DPP4 inhibitor alogliptin (ALO) combined with the TZD pioglitazone (PIO), vs ALO monotherapy or placebo (PBO), on ?-cell function and glycemic control in T2DM. Material and methods: A 16-week, two-center, randomized, double-blind, PBO-controlled, parallel-arm intervention study in 71 patients with well-controlled T2DM (age 59.1 ± 6.3 years; A1C 6.7 ± 0.1%) treated with metformin, sulfonylurea, orglinide monotherapy was conducted. Patients were treated with combined ALO 25 mg and PIO 30 mg daily or ALO 25 mg daily monotherapy or PBO. Main outcome measures included change in A1C and fasting plasma glucose (FPG) from baseline to week 16. In addition, change in ?-cell function parameters obtained from standardized meal tests at baseline and at week 16 was measured. Results: ALO/PIO and ALO decreased A1C from baseline by 0.9 ± 0.1 and 0.4 ± 0.2% respectively (both P<0.001 vs PBO). FPG was decreased to a greater extent by ALO/PIO compared with ALO monotherapy (P<0.01). ALO/PIO treatment improved ?-cell glucose sensitivity (vs PBO; P<0.001) and fasting secretory tone (vs PBO; P=0.001), while ALO monotherapy did not change ?-cell function parameters. All treatments were well tolerated. Conclusion: Short-term treatment with ALO/PIO or ALO improved glycemic control in well-controlled T2DM patients, but only combined ALO/PIO improved ?-cell function. These data support that initial combination therapy with a DPP4 inhibitor and TZD to address multiple core defects in T2DM may be a sensible approach. © 2014 European Society of Endocrinology Printed in Great Britain.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
