aseline (mean) 196 201 205 197 204 197
Change from baseline (adjusted mean†) 6 -17 -27 -29 -47 -64
Difference from placebo (adjusted mean†) (95% CI) -23‡
(-33, -14) -33‡
(-43, -24) -35‡
(-45, -26) -53‡
(-62, -43) -70‡
(-79, -60)
2-hour PPG (mg/dL) N = 129 N = 136 N = 141 N = 138 N = 147 N = 152
Baseline (mean) 277 285 293 283 292 287
Change from baseline (adjusted mean†) 0 -52 -53 -78 -93 -117
Difference from placebo (adjusted mean†) (95% CI) -52‡
(-67, -37) -54‡
(-69, -39) -78‡
(-93, -63) -93‡
(-107, -78) -117‡
(-131, -102)
*
All Patients Treated Population; least squares means adjusted for prior antihyperglycemic therapy and baseline value.
Figure 1: Mean Change from Baseline for A1C (%) over 24 Weeks with Sitagliptin and Metformin, Alone and in Combination as Initial Therapy in Patients with Type 2 Diabetes*
In addition, this study included patients (N=117) with more severe hyperglycemia (A1C >11% or blood glucose >280 mg/dL) who were treated with twice daily open-label sitagliptin 50 mg and metformin 1000 mg. In this group of patients, the mean baseline A1C value was 11.2%, mean FPG was 314 mg/dL, and mean 2-hour PPG was 441 mg/dL. After 24 weeks, mean decreases from baseline of -2.9% for A1C, -127 mg/dL for FPG, and -208 mg/dL for 2-hour PPG were observed.
Initial combination therapy or maintenance of combination therapy may not be appropriate for all patients. These management options are left to the discretion of the health care provider.
Active-Controlled Study vs Glipizide in Combination with Metformin
The efficacy of sitagliptin was eva luated in a 52-week, double-blind, glipizide-controlled noninferiority trial in patients with type 2 diabetes. Patients not on treatment or on other antihyperglycemic agents entered a run-in treatment period of up to 12 weeks duration with metformin monotherapy (dose of ≥1500 mg per day) which included washout of medications other than metformin, if applicable. After the run-in period, those with inadequate glycemic control (A1C 6.5% to 10%) were randomized 1:1 to the addition of sitagliptin 100 mg once daily or glipizide for 52 weeks. Patients receiving glipizide were given an initial dosage of 5 mg/day and then electively titrated over the next 18 weeks to a maximum dosage of 20 mg/day as needed to optimize glycemic control. Thereafter, the glipizide dose was to be kept constant, except for down-titration to prevent hypoglycemia. The mean dose of glipizide after the titration period was 10 mg.
After 52 weeks, sitagliptin and glipizide had similar mean reductions from baseline in A1C in the intent-to-treat analysis (Table 10). These results were consistent with the per protocol analysis (Figure 2). A conclusion in favor of the non-inferiority of sitagliptin to glipizide may be limited to patients with baseline A1C comparable to those included in the study (over 70% of patients had baseline A1C <8% and over 90% had A1C <9%).
Table 10: Glycemic Parameters in a 52-Week Study Comparing Sitagliptin to Glipizide as Add-On Therapy in Patients Inadequately Controlled on Metformin (Intent-to-Treat Population)* Sitagliptin 100 mg Glipizide
*
The intent-to-treat analysis used the patients' last observation in the study prior to discontinuation.
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