Table 14: Glycemic Parameters at Final Visit (24-Week Study) for Sitagliptin as Add-On Combination Therapy with Glimepiride, with or without Metformin*   Sitagliptin 100 mg + Glimepiride Placebo + Glimepiride Sitagliptin 100 mg + Glimepiride + Metformin Placebo + Glimepiride + Metformin
*
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.
§
p<0.01 compared to placebo. 
     
A1C (%) N = 102 N = 103 N = 115 N = 105
  Baseline (mean) 8.4 8.5 8.3 8.3
  Change from baseline (adjusted mean†) -0.3 0.3 -0.6 0.3
  Difference from placebo (adjusted mean†) (95% CI) -0.6‡
(-0.8, -0.3)  -0.9‡
(-1.1, -0.7) 
  Patients (%) achieving A1C <7% 11 (11%) 9 (9%) 26 (23%) 1 (1%)
FPG (mg/dL) N = 104 N = 104 N = 115 N = 109
  Baseline (mean) 183 185 179 179
  Change from baseline (adjusted mean†) -1 18 -8 13
  Difference from placebo (adjusted mean†) (95% CI) -19§
(-32, -7)  -21‡
(-32, -10) 

Add-on Combination Therapy with Insulin (with or without Metformin)

A total of 641 patients with type 2 diabetes participated in a 24-week, randomized, double-blind, placebo-controlled study designed to assess the efficacy of sitagliptin as add-on to insulin therapy (with or without metformin). The racial distribution in this study was approximately 70% white, 18% Asian, 7% black, and 5% other groups. Approximately 14% of the patients in this study were Hispanic. Patients entered a 2-week, single-blind run-in treatment period on pre-mixed, long-acting, or intermediate-acting insulin, with or without metformin (≥1500 mg per day). Patients using short-acting insulins were excluded unless the short-acting insulin was administered as part of a pre-mixed insulin. After the run-in period, patients with inadequate glycemic control (A1C 7.5% to 11%) were randomized to the addition of either 100 mg of sitagliptin or placebo, administered once daily. Patients were on a stable dose of insulin prior to enrollment with no changes in insulin dose permitted during the run-in period. Patients who failed to meet specific glycemic goals during the double-blind treatment period were to have uptitration of the background insulin dose as rescue therapy.

The median daily insulin dose at baseline was 42 units in the patients treated with sitagliptin and 45 units in the placebo-treated patients. The median change from baseline in daily dose of insulin was zero for both groups at the end of the study. In combination with insulin (with or without metformin), sitagliptin provided significant improvements in A1C, FPG, and 2-hour PPG compared to placebo (Table 15). Both treatment groups had an adjusted mean increase in body weight of 0.1 kg from baseline to Week 24. There was an increased rate of hypoglycemia in patients treated with sitagliptin. [See Warnings and Precautions (5.5); Adverse Reactions (6.1).]

Table 15: Glycemic Parameters at F