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

Nov 23, 2004
Font Size
A
A
A
Date Presented:
01/01/2004
Date Published:
01/01/2005
Date Updated:
11/23/2004
Original Posted Date:
11/23/2004
References

Description:

This was a multicenter, randomized double-blinded clinical trial designed to test the lipid-altering effects of two insulin-sensitizing drugs (pioglitazone vs. rosiglitazone) in patients with type 2 diabetes with dyslipidemia.

Hypothesis:

Pioglitazone would be associated with improved triglyceride levels compared to rosiglitazone when administered to type 2 diabetic patients with dyslipidemia.

Study Design

Patients Enrolled: 802
Mean Follow Up: 24 months
Mean Patient Age: Mean 56 years
Female: 46

Patient Populations:

Patients with type 2 diabetes and dyslipidemia not currently taking lipid-lowering agents. Triglycerides had to be ≥150 mg/dl and <600 mg/dl, and LDL had to be <130 mg/dl. HgA1c had to be 7-11% in patients not on a hypoglycemic agent and 7-9.5% in patients on a prior oral hypoglycemic agent.

Exclusions:

Prior lipid-lowering therapy, insulin therapy, or prior therapy for diabetes with more than one oral agent

Primary Endpoints:

Triglyceride levels at the end of the 24-week follow-up period

Secondary Endpoints:

Concentrations of other lipids (HDL, total cholesterol, LDL), LDL particle size, LDL particle concentration, CRP, PAI-1, and free fatty acid concentration

Drug/Procedures Used:

Four-week washout from any oral hypoglycemic agents (placebo administered), followed by randomization to either pioglitazone 30 mg qd or rosiglitazone 4 mg qd for 12 weeks. After this 12-week period, the doses of the study medications were increased to pioglitazone 45 mg qd or rosiglitazone 4 mg bid (patients were continued on the same agent assigned by the initial randomization).

Concomitant Medications:

Standard medical therapy. All other oral hypoglycemic agents were discontinued.

Principal Findings:

A total of 802 patients were randomized, and 735 patients were actually treated with one of the two study agents, with 80% of patients completing the study. The baseline characteristics were well-balanced in both groups, with a mean body mass index of 33 kg/meter-squared, a mean hemoglobin A1c (HgA1c) of 7.6%, triglyceride level of 258 mg/dl, low-density lipoprotein (LDL) of 107 mg/dl, and high-density lipoprotein (HDL) of 39 mg/dl.

At the end of the follow-up period, there was no significant difference in HgA1c between the two study groups, but there was a statistically significant difference in triglyceride levels between the two groups, evident as early as week 4 of treatment. In patients treated with pioglitazone, triglyceride levels decreased by 51.9 mg/dl, while increasing in the rosiglitazone group by 13.1 mg/dl (p<0.001). HDL increased by 5.2 mg/dl in the pioglitazone group versus 2.4 mg/dl in the rosiglitazone group (p<0.001), and LDL increased by 12.3 mg/dl versus 21.3 mg/dl (p<0.001). LDL particle size increased to a greater extent in the pioglitazone group, and LDL particle concentration decreased in this group as well, while increasing in the rosiglitazone group.

Apo-B concentration mildly increased in the pioglitazone group, while increasing to a greater extent in the rosiglitazone group (p<0.001). There were no significant differences between groups in C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), or free fatty acid concentrations.

Interpretation:

In this randomized head-to-head study of two insulin-sensitizing agents in patients with type 2 diabetes and dyslipidemia, different effects on the lipid profile were noted between the two study agents pioglitazone and rosiglitazone. Patients treated with pioglitazone had better lipid profiles after the treatment period compared to those treated with rosiglitazone.

One caveat limiting the generalizability of this study, however, is that it is unclear what effect therapy with one of these agents in conjunction with statin therapy would have on the lipid profile in a similar patient population, as patients already on statins were excluded from the study. Additionally, whether these changes translate into clinical outcomes remains to be determined. Nonetheless, studies such as this one emphasize the importance of head-to-head comparisons and limit assumptions of uniform class effects between similar agents.

References:

Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care. 2005 Jul;28(7):1547-54.

Presented by Ronald B. Goldberg at the American Heart Association Scientific Sessions, November 2004, New Orleans, LA.

Keywords: Follow-Up Studies, Diabetes Mellitus, Type 2, Insulins, Particle Size, Hypercholesterolemia, Dyslipidemias, C-Reactive Protein, Hemoglobins, Body Mass Index, Plasminogen Inactivators, Hypoglycemic Agents, Fatty Acids, Nonesterified, Triglycerides, Thiazolidinediones


< Back to Listings