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Pioglitazone and cardiovascular risk reduction: time for a second look?

ABSTRACT: Insulin resistance, a fundamental pathophysiological abnormality in patients with type 2 diabetes, is associated with increased cardiovascular (CV) disease risk. In diabetes management, the macrovascular impact of antihyperglycemic agents that do not improve insulin sensitivity has generally been disappointing. In contrast, glucose-lowering drugs that work as insulin sensitizing agents have been postulated to reduce CV complications. The data to support this hypothesis have, however, been inconsistent. The impact of thiazolidinediones on macrovascular events is of particular interest. In this review, we discuss the results of trials reporting CV outcomes in patients treated with thiazolidinediones. We focus on the findings of the recent Insulin Resistance Intervention after Stroke trial that demonstrated a beneficial effect of pioglitazone on CV outcomes in stroke patients with insulin resistance. We discuss the Insulin Resistance Intervention after Stroke results and its implications for clinical practice. We discuss the selective use of pioglitazone as secondary prevention to reduce CV risk in insulin resistant patients.

SUBMITTER: Perdigoto AL

PROVIDER: S-EPMC6768516 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Pioglitazone and cardiovascular risk reduction: time for a second look?

Perdigoto Ana L AL Young Lawrence H LH Inzucchi Silvio E SE

Cardiovascular endocrinology 20170517 2

Insulin resistance, a fundamental pathophysiological abnormality in patients with type 2 diabetes, is associated with increased cardiovascular (CV) disease risk. In diabetes management, the macrovascular impact of antihyperglycemic agents that do not improve insulin sensitivity has generally been disappointing. In contrast, glucose-lowering drugs that work as insulin sensitizing agents have been postulated to reduce CV complications. The data to support this hypothesis have, however, been incons ...[more]

PMID: 31646121

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Project description: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.

Dataset Information

Pioglitazone and cardiovascular risk reduction: time for a second look?

Publications

Pioglitazone and cardiovascular risk reduction: time for a second look?

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