dalcetrapib and Diabetes-Mellitus--Type-2

Incident type 2 diabetes is common among patients with recent acute coronary syndrome and is associated with an adverse prognosis. Some data suggest that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes. We compared the effect of treatment with the CETP inhibitor dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome.. At baseline, 10,645 patients (67% of the trial cohort) did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 403 of 5,326 patients (7.6%) assigned to dalcetrapib and in 516 of 5,319 (9.7%) assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68-0.88;. In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.

Topics: Acute Coronary Syndrome; Aged; Amides; Anticholesteremic Agents; Blood Glucose; Cohort Studies; Coronary Disease; Diabetes Mellitus, Type 2; Esters; Female; Humans; Incidence; Male; Middle Aged; Prediabetic State; Risk Factors; Risk Reduction Behavior; Sulfhydryl Compounds

Mixed dyslipidaemia, characterized by low levels of high-density lipoprotein cholesterol (HDL-C) and high levels of triglycerides, is common in patients with type 2 diabetes mellitus (T2DM) and/or metabolic syndrome. Dalcetrapib effectively increases HDL-C levels by modulating cholesteryl ester transfer protein (CETP) activity. The aim of this analysis was to investigate the lipid modifying efficacy and safety of dalcetrapib in patients with T2DM and/or metabolic syndrome.. Post hoc analysis of dalcetrapib therapy in five placebo-controlled, Phase II trials (4-48 weeks of duration) involving T2DM and/or metabolic syndrome, in dyslipidaemic patients with coronary heart disease (CHD) or CHD risk equivalent.. Both in patients with and without T2DM and/or metabolic syndrome, dalcetrapib decreased CETP activity by 26-58% and increased HDL-C levels by 23-34%, depending on dose and duration of treatment. Dalcetrapib did not significantly affect low-density lipoprotein cholesterol (LDL-C) or apolipoprotein B levels. Treatment with dalcetrapib was generally well tolerated with a similar number of adverse events reported between patient groups and between those receiving dalcetrapib compared with placebo.. Dalcetrapib similarly decreased CETP activity and increased HDL-C levels in patients with and without T2DM or metabolic syndrome; the ongoing Phase III dal-OUTCOMES study will help to determine if dalcetrapib's improvement in lipid levels also reduces cardiovascular morbidity and mortality.

Topics: Amides; Anticholesteremic Agents; Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, LDL; Clinical Trials, Phase II as Topic; Controlled Clinical Trials as Topic; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dyslipidemias; Esters; Female; Humans; Male; Metabolic Syndrome; Middle Aged; Netherlands; Risk Assessment; Sulfhydryl Compounds; Triglycerides