ger;
Least squares means adjusted for prior antihyperglycemic therapy status and baseline A1C value.
A1C (%) N = 576 N = 559
Baseline (mean) 7.7 7.6
Change from baseline (adjusted mean†) -0.5 -0.6
FPG (mg/dL) N = 583 N = 568
Baseline (mean) 166 164
Change from baseline (adjusted mean†) -8 -8
*
The per protocol population (mean baseline A1C of 7.5%) included patients without major protocol violations who had observations at baseline and at Week 52.
Figure 2: Mean Change from Baseline for A1C (%) Over 52 Weeks in a Study Comparing Sitagliptin to Glipizide as Add-On Therapy in Patients Inadequately Controlled on Metformin (Per Protocol Population)*
The incidence of hypoglycemia in the sitagliptin group (4.9%) was significantly (p<0.001) lower than that in the glipizide group (32.0%). Patients treated with sitagliptin exhibited a significant mean decrease from baseline in body weight compared to a significant weight gain in patients administered glipizide (-1.5 kg vs +1.1 kg).
Add-on Combination Therapy with Pioglitazone
A total of 353 patients with type 2 diabetes participated in a 24-week, randomized, double-blind, placebo-controlled study designed to 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 Ther
