Sitagliptin Add-on Therapy in Patients with Type 2 Diabetes Inadequately Controlled on the Combination of Metformin and Glimepiride

A total of 441 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 glimepiride, with or without metformin. Patients entered a run-in treatment period on glimepiride (≥4mg per day) alone or glimepiride in combination with metformin (≥1500mg per day). After a dose-titration and dose-stable run-in period of up to 16 weeks and a 2-week placebo run-in period, patients with inadequate glycemic control (A1C 7.5% to 10.5%) were randomized to the addition of either 100mg of sitagliptin or placebo, administered once daily. Patients who failed to meet specific glycemic goals during the studies were treated with pioglitazone rescue.

Patients receiving sitagliptin with metformin and glimepiride had significant improvements in A1C and FPG compared to patients receiving placebo with metformin and glimepiride (Table 6), with mean reductions from baseline relative to placebo in A1C of -0.9% and in FPG of -21 mg/dL. Rescue therapy was used in 8% of patients treated with add-on sitagliptin 100mg and 29% of patients treated with add-on placebo. The patients treated with add-on sitagliptin had a mean increase in body weight of 1.1kg vs. add-on placebo (+0.4kg vs. -0.7 kg). In addition, add-on sitagliptin resulted in an increased rate of hypoglycemia compared to add-on placebo. [See Warnings and Precautions (5.9); Adverse Reactions (6.1).]

Table 6: Glycemic Parameters at Final Visit (24-Week Study) for Sitagliptin in Combination with Metformin and Glimepiride*  Sitagliptin 100 mg
+ Metformin
and Glimepiride Placebo
+ Metformin
and Glimepiride
*
Intent-to-treat population using last observation on study prior to pioglitazone rescue therapy.
†
Least squares means adjusted for prior antihyperglycemic therapy status and baseline value.
‡
p<0.001 compared to placebo.
A1C (%) N = 115 N = 105
Baseline (mean) 8.3 8.3
Change from baseline (adjusted mean†) -0.6 0.3
Difference from placebo (adjusted mean†)
(95% CI) -0.9‡
(-1.1, -0.7) 
Patients (%) achieving A1C <7% 26 (23%) 1 (1%)
FPG (mg/dL)  N = 115 N = 109
Baseline (mean)  179 179
Change from baseline (adjusted mean†) -8 13
Difference from placebo (adjusted mean†)
(95% CI) -21‡
(-32, -10) 

Sitagliptin Add-on Therapy in Patients with Type 2 Diabetes Inadequately Controlled on the Combination of Metformin and Rosiglitazone

A total of 278 patients with type 2 diabetes participated in a 54-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of sitagliptin in combination with metformin and rosiglitazone. Patients on dual therapy with metformin ≥1500mg/day and rosiglitazone ≥4mg/day or with metformin ≥1500mg/day and pioglitazone ≥30mg/day (s