The addition of AVANDIA to either metformin, a sulfonylurea, or insulin resulted in significant reductions in hyperglycemia compared to any of these agents alone. These results are consistent with an additive effect on glycemic control when AVANDIA is used as combination therapy. Patients with lipid abnormalities were not excluded from clinical trials of AVANDIA. In all 26-week controlled trials, across the recommended dose range, AVANDIA as monotherapy was associated with increases in total cholesterol, LDL, and HDL and decreases in free fatty acids. These changes were statistically significantly different from placebo or glyburide controls (see Table 2). Increases in LDL occurred primarily during the first 1 to 2 months of therapy with AVANDIA and LDL levels remained elevated above baseline throughout the trials. In contrast, HDL continued to rise over time. As a result, the LDL/ HDL ratio peaked after 2 months of therapy and then appeared to decrease over time. Because of the temporal nature of lipid changes, the 52-week glyburide-controlled study is most pertinent to assess long-term effects on lipids. At baseline, week 26, and week 52, mean LDL/ HDL ratios were 3.1, 3.2, and 3.0, respectively, for AVANDIA 4 mg twice daily. The corresponding values for glyburide were 3.2, 3.1, and 2.9. The differences in change from baseline between AVANDIA and glyburide at week 52 were statistically significant. The pattern of LDL and HDL changes following therapy with AVANDIA in combination with other hypoglycemic agents were generally similar to those seen with AVANDIA in monotherapy. The changes in triglycerides during therapy with AVANDIA were variable and were generally not statistically different from placebo or glyburide controls. Table 2. Summary of Mean Lipid Changes in 26-Week Placebo-Controlled and 52-Week Glyburide-Controlled Monotherapy Studies Placebo-controlled Studies Week 26 Glyburide-controlled Study Week 26 and Week 52 Placebo AVANDIA Glyburide Titration AVANDIA 8 mg 4 mg daily * 8 mg daily * Wk 26 Wk 52 Wk 26 Wk 52 | ||||
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