Abstract
BackgroundType 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors. The authors aimed to assess the relative effectiveness of pioglitazone (Pio), metformin (Met) and any sulfonylurea (SU) combinations in non-insulin-treated T2D patients who were failing previous hypoglycemic therapy.MethodsOver a 1-year period, two multicenter, open-labeled, controlled, 1-year, prospective, observational studies evaluated patients with T2D (n = 4585) from routine clinical practice in Spain and Greece with the same protocol. Patients were eligible if they had been prescribed Pio + SU, Pio + Met or SU + Met serving as a control cohort, once they had failed with previous therapy. Anthropometric measurements, lipid and glycemic profiles, blood pressure, and the proportions of patients at microvascular and macrovascular risk were assessed.ResultsAll study treatment combinations rendered progressive 6-month and 12-month lipid, glycemic, and blood pressure improvements. Pio combinations, especially Pio + Met, were associated with increases in HDL-cholesterol and decreases in triglycerides and in the atherogenic index of plasma. The proportion of patients at high risk decreased after 12 months in all study cohorts. Minor weight changes (gain or loss) and no treatment-related fractures occurred during the study. The safety profile was good and proved similar among treatments, except for more hypoglycemic episodes in patients receiving SU and for the occurrence of edema in patients using Pio combinations. Serious cardiovascular events were rarely reported.ConclusionsIn patients with T2D failing prior hypoglycemic therapies, Pio combinations with SU or Met (especially Pio + Met) improved blood lipid and glycemic profiles, decreasing the proportion of patients with a high microvascular or macrovascular risk. The combination of Pio with SU or Met may therefore be recommended for T2D second-line therapy in the routine clinical practice, particularly in patients with dyslipidemia.
Highlights
Type 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors
It has been suggested that Pio reduces hyperglycemia by enhancing insulin sensitivity through peroxisome proliferator-activated receptor (PPAR)-g binding, but it influences lipid metabolism and represses the endothelial inflammatory gene expression involved in atherosclerosis development by binding PPAR-a receptors [7,8]
Beyond a beneficial effect in glycemic control in patients with T2D, Pio combinations evaluated in this study improved various metabolic variables associated with cardiovascular risk
Summary
Type 2 diabetes (T2D) is strongly associated with cardiovascular risk and requires medications that improve glycemic control and other cardiovascular risk factors. About half of deaths in patients with T2D are caused by CVD, predominantly due to Pioglitazone (Pio) belongs to the group of thiazolidinediones (TZDs), agents that diminish insulin resistance primarily by selective binding to peroxisome-proliferator-activated receptor-g (PPAR-g). It has been suggested that Pio reduces hyperglycemia by enhancing insulin sensitivity through PPAR-g binding, but it influences lipid metabolism and represses the endothelial inflammatory gene expression involved in atherosclerosis development by binding PPAR-a receptors [7,8]. There is a debate surrounding the long-term risk/benefit ratio of TZDs, because TZDs’ pleiotropic effects, derived from the many actions of the genes activated by PPAR-g agonism, may entail side effects which would diminish or even counteract their positive effects, resulting in a net increase in the risk of macrovascular complications [9]
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