inal Visit (24-Week Study) for Sitagliptin as Add-on Combination Therapy with Insulin* Sitagliptin 100 mg + Insulin (+/- Metformin) Placebo + Insulin (+/- Metformin)
*
Intent-to-treat population using last observation on study prior to rescue therapy.
†
Least squares means adjusted for metformin use at the screening visit (yes/no), type of insulin used at the screening visit (pre-mixed vs. non-pre-mixed [intermediate- or long-acting]), and baseline value.
‡
Treatment by stratum interaction was not significant (p>0.10) for metformin stratum and for insulin stratum.
§
p<0.001 compared to placebo.
A1C (%) N = 305 N = 312
Baseline (mean) 8.7 8.6
Change from baseline (adjusted mean†) -0.6 -0.1
Difference from placebo (adjusted mean†,‡) (95% CI) -0.6§ (-0.7, -0.4)
Patients (%) achieving A1C <7% 39 (12.8%) 16 (5.1%)
FPG (mg/dL) N = 310 N = 313
Baseline (mean) 176 179
Change from baseline (adjusted mean†) -18 -4
Difference from placebo (adjusted mean†) (95% CI) -15§ (-23, -7)
2-hour PPG (mg/dL) N = 240 N = 257
Baseline (mean) 291 292
Change from baseline (adjusted mean†) -31 5
Difference from placebo (adjusted mean†) (95% CI) -36§ (-47, -25)
14.2 Simvastatin Clinical Studies
Reductions in Risk of CHD Mortality and Cardiovascular Events
In 4S, the effect of therapy with simvastatin on total mortality was assessed in 4444 patients with CHD and baseline total cholesterol 212-309 mg/dL (5.5-8.0 mmol/L). In this multicenter, randomized, double-blind, placebo-controlled study, patients were treated with standard care, including diet, and either simvastatin 20-40 mg/day (n=2221) or placebo (n=2223) for a median duration of 5.4 years. Over the course of the study, treatment with simvastatin led to mean reductions in total-C, LDL-C and TG of 25%, 35%, and 10%, respectively, and a mean increase in HDL-C of 8%. Simvastatin significantly reduced the risk of mortality by 30% (p=0.0003, 182 deaths in the simvastatin group vs 256 deaths in the placebo group). The risk of CHD mortality was significantly reduced by 42% (p=0.00001, 111 vs 189 deaths). There was no statistically significant difference between groups in non-cardiovascular mortality. Simvastatin significantly decreased the risk of having major coronary events (CHD mortality plus hospital-verified and silent non-fatal myocardial infarction [MI]) by 34% (p<0.00001, 431 vs 622 patients with one or more events). The risk of having a hospital-verified non-fatal MI was reduced by 37%. Simvastatin significantly reduced the risk for undergoing myocardial revascularization procedures (coronary artery bypass grafting or percutaneous transluminal coronary angioplasty) by 37% (p<0.00001, 252 vs 383 patients). Simvastatin significantly reduced the risk of fatal plus non-fatal cerebrovascular events (combined stroke and transient ischemic attacks) by 28% (p=0.033, 75 vs 102 patients). Simvastatin reduced the risk of major coronary events to a similar extent across the range of baseline total and LDL cholesterol levels. Because there were only 53 female deaths, the effect of simvastatin on mortality in women could not be adequately assessed. However, simvastatin significantly lessened the risk of havi
