P6193Dalcetrapib reduces incident diabetes in patients with recent acute coronary syndrome

Abstract Background Among patients with acute coronary syndrome (ACS) who do not have diabetes, incident diabetes is common and associated with an adverse prognosis. Some data suggest that high density lipoprotein (HDL) has favourable effects on beta cell function and that cholesteryl ester transfer protein (CETP) inhibitors reduce incident type 2 diabetes in conjunction with increased HDL cholesterol (HDL-C) concentration. Dalcetrapib is a CETP inhibitor under ongoing evaluation as a potential cardiovascular therapy. Purpose We compared the effect of treatment with dalcetrapib or placebo on incident diabetes in patients with recent acute coronary syndrome (ACS). Methods In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg or placebo daily, beginning 4–12 weeks after ACS. Absence of diabetes at baseline was based upon medical history, no use of diabetes medication, haemoglobin A1c <6.5%, and plasma glucose level <7 mmol/L (if measured under fasting conditions) or <11.1 mmol/L (if measured under non-fasting conditions). Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, use of a diabetes medication, HbA1c ≥6.5%, or two measurements of plasma glucose ≥7 mmol/L (fasting) or ≥11.1 mmol/L (non-fasting). The association of incident diabetes with baseline and on-treatment HDL-C was determined. Results At baseline, 10621 patients (67% of the trial cohort) did not have diabetes and formed the analysis cohort. Over median follow-up of 31 months, incident diabetes was identified in 392 of 5314 patients (7.4%) assigned to dalcetrapib and 505 of 5307 (9.5%) assigned to placebo (odds ratio [OR] 0.76; 95% confidence interval [CI] 0.66–0.87; P<0.001). This corresponds to an absolute reduction in incident diabetes of 2.1%, and a need to treat 47 patients (for 31 months) to prevent 1 case of diabetes. Kaplan-Meier estimates of the cumulative incidence of diabetes are shown in the Figure. Across both treatment groups, incident diabetes was inversely associated with baseline HDL-C (OR 0.98 for 1 mg/dL increase in baseline HDL-C; 95% CI 0.97–0.98, P<0.001). In the dalcetrapib group, there was a further inverse association of incident diabetes with the change in HDL-C on assigned treatment (OR 0.98 for 1 mg/dL increase in HDL-C from baseline; 95% CI 0.97–0.99, P=0.002). Dalcetrapib was safe and generally well-tolerated in the trial. Conclusions In patients with recent ACS who do not have diabetes at baseline, incident diabetes is common. Dalcetrapib treatment reduced the relative risk of incident diabetes by 24% and the absolute risk by 2.1% over a median of 31 months. The reduction in incident diabetes with dalcetrapib was associated with increased HDL-C on treatment. Acknowledgement/Funding The dal-OUTCOMES trial was funded by F. Hoffmann LaRoche

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