Figure 1: Mean Change from Baseline for A1C (%) over 24 Weeks with Sitagliptin and Metformin, Alone and in Combination in Patients with Type 2 Diabetes Inadequately Controlled with Diet and Exercise†

In addition, this study included patients (N=117) with more severe hyperglycemia (A1C >11% or blood glucose >280mg/dL) who were treated with twice daily open-label sitagliptin 50mg and metformin 1000mg. In this group of patients, the mean baseline A1C value was 11.2%, mean FPG was 314mg/dL, and mean 2-hour PPG was 441mg/dL. After 24 weeks, mean decreases from baseline of -2.9% for A1C, -127mg/dL for FPG, and -208 mg/dL for 2-hour PPG were observed.

Initial combination therapy or maintenance of combination therapy should be individualized and are left to the discretion of the health care provider.

Sitagliptin Add-on Therapy in Patients with Type 2 Diabetes Inadequately Controlled on Metformin Alone

A total of 701 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 metformin. Patients already on metformin (N=431) at a dose of at least 1500mg per day were randomized after completing a 2-week, single-blind placebo run-in period. Patients on metformin and another antihyperglycemic agent (N=229) and patients not on any antihyperglycemic agents (off therapy for at least 8 weeks, N=41) were randomized after a run-in period of approximately 10 weeks on metformin (at a dose of at least 1500mg per day) in monotherapy. Patients 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.

In combination with metformin, sitagliptin provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo with metformin (Table 5). Rescue glycemic therapy was used in 5% of patients treated with sitagliptin 100mg and 14% of patients treated with placebo. A similar decrease in body weight was observed for both treatment groups.

Table 5: Glycemic Parameters at Final Visit (24-Week Study) of Sitagliptin as Add-on Combination Therapy with Metformin*  Sitagliptin 100mg QD
+ Metformin Placebo
+ Metformin
*
Intent-to-treat population using last observation on study prior to pioglitazone rescue therapy.
†
Least squares means adjusted for prior antihyperglycemic therapy and baseline value.
‡
p<0.001 compared to placebo + metformin.
A1C (%) N = 453 N = 224
Baseline (mean) 8.0 8.0
Change from baseline (adjusted mean†) -0.7 -0.0
Difference from placebo + metformin (adjusted mean†)
(95% CI) -0.7‡
(-0.8, -0.5) 
Patients (%) achieving A1C <7% 213 (47%) 41 (18%)
FPG (mg/dL)  N = 454 N = 226
Baseline (mean)  170 174
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