A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia

Ronald B. Goldberg, MD; David M. Kendall, MD; Mark A. Deeg, MD, PHD; John B. Buse, MD, PHD; Anthony J. Zagar, MS; Jane A. Pinaire, PHD; Meng H. Tan, MD; Mehmood A. Khan, MD; Alfonso T. Perez, MD; Scott J. Jacober, DO

Disclosures

Diabetes Care. 2005;28(7):1547-1554. 

In This Article

Results

Figure 1 summarizes patient flow through the study. Similar numbers of subjects completed therapy for the pioglitazone and rosiglitazone groups. The distribution of subjects among the various withdrawal categories was also similar between treatment groups.

Patient flow through the study.

There were no statistically significant differences between the treatment groups in respect to demographics, baseline characteristics, and laboratory measurements with the exception of fasting C-peptide levels, which were lower in subjects randomly assigned to rosiglitazone ( Table 1 ).

Figure 2 shows the 24-week time course for fasting triglycerides, HDL cholesterol, non-HDL cholesterol, LDL cholesterol, and A1C. Baseline and end point values for each are found in Table 2 .

Comparison of fasting triglyceride (A), HDL cholesterol (B), non-HDL cholesterol (C), LDL cholesterol (D), and mean A1C (E) levels observed during 24 weeks of therapy with pioglitazone (PIO) and rosiglitazone (ROSI). LDL cholesterol levels were directly measured (not calculated). Patients were randomly assigned to either 12 weeks of 30 mg/day pioglitazone followed by 12 weeks of 45 mg/day pioglitazone () or 12 weeks of 4 mg/day rosiglitazone once daily followed by 12 weeks of 4 mg rosiglitazone twice daily (). Vertical bars represent SE. *P < 0.001 between treatment groups; +P < 0.05 between treatment groups.

By the first posttherapy visit, triglyceride levels were significantly decreased with pioglitazone and significantly increased with rosiglitazone compared with baseline. Differences in triglyceride levels between treatment groups were significant at every time point (P < 0.001) (Fig. 2A). By week 24, triglyceride levels in pioglitazone-treated subjects were significantly reduced by 51.9 ± 7.8 mg/dl (12.0 ± 3.0%, median of 19.8%) below baseline ( Table 2 ), whereas triglyceride levels in rosiglitazone-treated subjects were elevated by 13.1 ± 7.8 mg/dl (14.9 ± 3.1%, median of 3.5%) above baseline (the percent change represents the mean of the individual percent changes from baseline). The 95% CI (based on the ANCOVA model) for the mean change from baseline to the last observed value was -67.2 to -36.6 mg/dl in the pioglitazone group and -2.2 to +28.5 mg/dl in the rosiglitazone group. The mixed-model repeated-measures results for change from baseline triglyceride level (data not shown) as well as the results from an analysis of study completers (data not shown) were similar to the LOCF results.

Both pioglitazone and rosiglitazone increased HDL cholesterol over time, but mean changes from baseline to end point were significantly greater with pioglitazone compared with rosiglitazone, respectively: 5.2 ± 0.5 mg/dl (14.9 ± 1.2%) versus 2.4 ± 0.5 mg/dl (7.8 ± 1.2%) (P < 0.001) ( Table 2 ). The differences in HDL cholesterol levels between treatment groups were significant at every time point (P < 0.001) (Fig. 2B).

Non-HDL cholesterol levels remained relatively constant in pioglitazone-treated subjects but were markedly increased with rosiglitazone therapy over the treatment period, such that the differences between treatment groups were significant at every time point (P < 0.001) (Fig. 2C). By week 24, non-HDL cholesterol levels in pioglitazone-treated subjects were 3.6 ± 1.9 mg/dl (3.8 ± 1.3%) above baseline, whereas levels in rosiglitazone-treated subjects increased 25.7 ± 2.0 mg/dl (18.6 ± 1.3%) above baseline (P < 0.001 between treatments) ( Table 2 ).

Both pioglitazone and rosiglitazone also increased LDL cholesterol over time, but mean changes from baseline to end point were significantly less with pioglitazone compared with rosiglitazone, respectively: 12.3 ± 1.6 mg/dl (15.7 ± 1.9%) versus 21.3 ± 1.6 mg/dl (23.3 ± 1.9%) (P < 0.001) ( Table 2 ). The differences in LDL cholesterol levels between treatment groups were significant at every time point (P < 0.001) except at weeks 4 and 12 (Fig. 2D). Lastly, apolipoprotein B was unchanged in the pioglitazone group but significantly increased in the rosiglitazone group ( Table 2 ).

Figure 3 compares the effects of pioglitazone and rosiglitazone on LDL particle concentration and particle size at end point. These agents had opposing effects on particle concentration: a significant reduction was observed with pioglitazone, whereas rosiglitazone therapy resulted in a significant increase. Both agents increased particle size, but the increase observed with pioglitazone was significantly greater than that observed with rosiglitazone.

Comparison of mean LDL particle concentration (A) and particle size (B) at baseline and end point (24 weeks) for patients treated with pioglitazone (PIO) and rosiglitazone (ROSI). Vertical bars represent SE.

Both agents significantly improved glycemic control. Although statistical differences between treatment groups were observed for A1C values between weeks 4 and 12, these differences are not clinically significant (Fig. 2E). Furthermore, there was no difference between agents with respect to A1C or fasting plasma glucose changes at end point ( Table 2 ). No significant differences were observed between agents for changes in free fatty acid levels, PAI-1, C-reactive protein, and indices of insulin secretion and sensitivity ( Table 2 ).

Mean body weight changes from baseline were similar for both pioglitazone (2.0 ± 0.2 kg) and rosiglitazone (1.6 ± 0.2 kg) (P = 0.164). Additionally, no differences between agents were observed with regard to liver function tests (alanine aminotransferase and aspartate aminotransferase), creatine phosphokinase, blood pressure and heart rate, hemoglobin and hematocrit, hypoglycemic episodes, or adverse events including edema and congestive heart failure.

processing....