Effects of pioglitazone on the components of diabetic dyslipidaemia: Results of double-blind, multicentre, randomised studies

Abstract

A total of 3,713 patients with poorly controlled type 2 diabetes were enroled into four multicentre, double-blind studies and randomised to receive pioglitazone, sulphonylurea, metformin or a combination of two of these agents for up to 52 weeks. Data from patients with a lipid evaluation, at week 52, were pooled, and treatment groups were compared using analysis of covariance. Pioglitazone, alone or combined with metformin or sulphonylurea, resulted in mean decreases in triglycerides (-9 to -11%), total/HDL cholesterol ratio (-9 to -10%) and free fatty acid (-0.051 to -0.123 mmol/l) and mean increases in HDL cholesterol (17 to 20%). The sustained, favourable effects of pioglitazone on important components of diabetic dyslipidaemia may contribute to reduced cardiovascular disease risk, among patients with type 2 diabetes.

Impact of thiazolidenediones on serum lipoprotein levels

“…A similar result was found in a trial of TROG added to failed therapy with metformin plus sulfonylurea treatment [8]. Compared with sulfonylurea or metformin treatment, which reduced LDL cholesterol by 3.5% and 0.6% from baseline, respectively, PIO increased LDL cholesterol by 8.4% [13]. In dose-ranging studies, there did not seem to be a dose-dependent response and the effect appeared to be additive when PIO was added to other antihyperglycemic therapy [3,4,[12][13][14][15][16][17].…”

“…Compared with sulfonylurea or metformin treatment, which reduced LDL cholesterol by 3.5% and 0.6% from baseline, respectively, PIO increased LDL cholesterol by 8.4% [13]. In dose-ranging studies, there did not seem to be a dose-dependent response and the effect appeared to be additive when PIO was added to other antihyperglycemic therapy [3,4,[12][13][14][15][16][17]. There may be a time-related attenuation of the LDL-raising effect because there was no significant increase in LDL cholesterol in the PIO-treated group of the 3-year PROactive trial [18].…”

“…In retrospect, it is surprising that little attention to these differences was raised, because some of the TROG and ROSI trials were published in the same era. The advent of clinical trials with PIO led to the appreciation that treatment with this TZD, again in monotherapy, combined oral therapy, or with insulin, evoked a triglyceride response resembling the effect seen with TROG rather than with ROSI, as PIO treatment was consistently associated with a lowering of fasting triglyceride between 8% and 16% from the baseline value (triglyceride reduction of 10-60 mg/dL) [3,4,[12][13][14][15][16][17]. In most studies, the reduction of triglyceride levels with PIO significantly exceeded any effect associated with comparator sulfonylurea or metformin, and in studies of combination therapy with these agents PIO had at least a partly additive effect.…”

Pioglitazone Reduces Atherogenic Outcomes in Type 2 Diabetic Patients

“…Therefore, reduction of these atherogenic parameters by the agent might be beneficial for the prevention of atherosclerosis, including CHD, due to its anti-inflammatory effect, in diabetic patients. However, different from other reported studies [22][23][24] , we could not observe any significant change in other parameters, including TG, T-Cho, LDL-C, HDL-C, leptin, or adiponectin, although the value of TG decreased to 73% ( Fig. 2A) and that of adiponectin increased to 162.8% at the end of the study (Table 2).…”

“…Recent intervention trials have shown that insulin-sensitizing agents, including metformin and other TZDs, affect dyslipidemia [22][23][24] and the abnormal secretion of adipocytokines, such as adiponectin 25,26) , in diabetic patients; however, whether insulin-sensitizing agents such as pioglitazone could affect the levels of these potential risk factors for diabetic macroangiopathy remains undetermined.…”