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.
Among patients also receiving metformin, the median daily insulin (pre-mixed, intermediate or long acting) dose at baseline was 40 units in the sitagliptin-treated patients and 42 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. Patients receiving sitagliptin with metformin and insulin had significant improvements in A1C, FPG and 2-hour PPG compared to patients receiving placebo with metformin and insulin (Table8). The adjusted mean change from baseline in body weight was -0.3 kg in patients receiving sitagliptin with metformin and insulin and -0.2 kg in patients receiving placebo with metformin and insulin. There was an increased rate of hypoglycemia in patients treated with sitagliptin. [See Warnings and Precautions (5.9); Adverse Reactions (6.1).]
Table 8: Glycemic Parameters at Final Visit (24-Week Study) for Sitagliptin as Add-on Combination Therapy with Metformin and Insulin* *
Intent-to-treat population using last observation on study prior to rescue therapy.
†
Least squares mean adjusted for insulin use at the screening visit, type of insulin used at the screening visit (pre-mixed vs. non pre-mixed [intermediate- or long-acting]), and baseline value.
‡
Treatment by insulin stratum interaction was not significant (p >0.10).
§
p<0.001 compared to placebo.
Sitagliptin 100mg
+ Metformin
+ Insulin Placebo
+ Metformin
+ Insulin
A1C (%) N = 223 N = 229
Baseline (mean) 8.7 8.6
Change from baseline (adjusted mean†,‡) -0.7 -0.1
Difference from placebo (adjusted mean†) (95% CI) -0.5§ ( -0.7, -0.4)
Patients (%) achieving A1C (%) <7% 32 (14%) 12 (5%)
FPG (mg/dL) N = 225 N = 229
Baseline (mean) 173 176
Change from baseline (adjusted mean†) -22 -4
Difference from placebo (adjusted mean†) (95% CI) -18§ ( -28, -8.4)
2-hour PPG (mg/dL) N = 182 N = 189
Baseline (mean) 281 281
Change from baseline (adjusted mean†) -39 1
Difference from placebo (adjusted mean†) (95% CI) -40§ (-53, -28)
Sitagliptin Add-on Therapy vs. Glipizide Add-on Therapy in Patients with Type 2 Diabetes Inadequately Controlled on 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 ≥1500mg 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 100mg once daily or glipizide for 52 weeks. Patients receiving glipizide were given an initial dosage of 5mg/day and then electively titrated over the next 18 weeks to a maximum dosage of 20mg/day as needed to optimize glycemic control. Thereafter, the glipizide dose was to be kept constant, except for down-titration t
