o assess the efficacy of sitagliptin in combination with pioglitazone. Patients on any oral antihyperglycemic agent in monotherapy (N=212) or on a PPARγ agent in combination therapy (N=106) or not on an antihyperglycemic agent (off therapy for at least 8 weeks, N=34) were switched to monotherapy with pioglitazone (at a dose of 30-45 mg per day), and completed a run-in period of approximately 12 weeks in duration. After the run-in period on pioglitazone monotherapy, patients with inadequate glycemic control (A1C 7% to 10%) were randomized to the addition of either 100 mg of sitagliptin or placebo, administered once daily. Patients who failed to meet specific glycemic goals during the studies were treated with metformin rescue. Glycemic endpoints measured were A1C and fasting glucose.
In combination with pioglitazone, sitagliptin provided significant improvements in A1C and FPG compared to placebo with pioglitazone (Table 11). Rescue therapy was used in 7% of patients treated with sitagliptin 100 mg and 14% of patients treated with placebo. There was no significant difference between sitagliptin and placebo in body weight change.
Table 11 Glycemic Parameters at Final Visit (24-Week Study) for Sitagliptin in Add-on Combination Therapy with Pioglitazone * Sitagliptin 100 mg + Pioglitazone Placebo + Pioglitazone
*
Intent-to-treat population using last observation on study prior to metformin rescue therapy.
†
Least squares means adjusted for prior antihyperglycemic therapy status and baseline value.
‡
p<0.001 compared to placebo + pioglitazone.
A1C (%) N = 163 N = 174
Baseline (mean) 8.1 8.0
Change from baseline (adjusted mean†) -0.9 -0.2
Difference from placebo + pioglitazone (adjusted mean†) (95% CI) -0.7‡
(-0.9, -0.5)
Patients (%) achieving A1C <7% 74 (45%) 40 (23%)
FPG (mg/dL) N = 163 N = 174
Baseline (mean) 168 166
Change from baseline (adjusted mean†) -17 1
Difference from placebo + pioglitazone (adjusted mean†) (95% CI) -18‡
(-24, -11)
Initial Combination Therapy with Pioglitazone
A total of 520 patients with type 2 diabetes and inadequate glycemic control on diet and exercise participated in a 24-week, randomized, double-blind study designed to assess the efficacy of sitagliptin as initial therapy in combination with pioglitazone. Patients not on antihyperglycemic agents at study entry (<4 weeks cumulative therapy over the past 2 years, and with no treatment over the prior 4 months) with inadequate glycemic control (A1C 8% to 12%) immediately entered the 2-week single-blind placebo run-in period and then were randomized. Approximately equal numbers of patients were randomized to receive initial therapy with 100 mg of sitagliptin in combination with 30 mg of pioglitazone once daily or 30 mg of pioglitazone once daily as monotherapy. There was no glycemic rescue therapy in this study.
Initial therapy with the combination of sitagliptin and pioglitazone provided significant improvements in A1C, FPG, and 2-hour PPG compared to pioglitazone monotherapy (Table 12). The improvement in A1C was generally consistent across subgroups defined by gender, age, race, baseline BMI, baseline A1C, or duration of disease. In this study, patients treated with sitagliptin in combination with pioglitazone had a mean increase in body weight of 1.1 k |
