Dalcetrapib Reduces Risk of New-Onset Diabetes in Patients With Coronary Heart Disease

• Published in: Diabetes care Vol. 43; no. 5; pp. 1077 - 1084
• Main Authors: Schwartz, Gregory G., Leiter, Lawrence A., Ballantyne, Christie M., Barter, Philip J., Black, Donald M., Kallend, David, Laghrissi-Thode, Fouzia, Leitersdorf, Eran, McMurray, John J.V., Nicholls, Stephen J., Olsson, Anders G., Preiss, David, Shah, Prediman K., Tardif, Jean-Claude, Kittelson, John
• Format: Journal Article
• Language: English
• Published: United States American Diabetes Association 01.05.2020
• Subjects: Acute Coronary Syndrome - complications; Acute Coronary Syndrome - drug therapy; Acute Coronary Syndrome - epidemiology; Acute coronary syndromes; Aged; Amides - therapeutic use; Anticholesteremic Agents - therapeutic use; Blood Glucose - drug effects; Blood Glucose - metabolism; Cardiovascular disease; Cardiovascular diseases; Cholesteryl ester transfer protein; Cohort Studies; Coronary artery disease; Coronary Disease - complications; Coronary Disease - drug therapy; Coronary Disease - epidemiology; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - prevention & control; Diagnostic systems; Emerging Therapies: Drugs and Regimens; Esters - therapeutic use; Female; Glucose; Health risks; Health services; Heart diseases; Hemoglobin; Humans; Hyperglycemia; Incidence; Male; Middle Aged; Patients; Prediabetic State - complications; Prediabetic State - drug therapy; Prediabetic State - epidemiology; Prediabetic State - pathology; Research design; Risk Factors; Risk management; Risk Reduction Behavior; Sulfhydryl Compounds - therapeutic use
• ISSN: 0149-5992; 1935-5548; 1935-5548
• DOI: 10.2337/dc19-2204

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. In the dal-OUTCOMES trial, 15,871 patients were randomly assigned to treatment with dalcetrapib 600 mg daily or placebo, beginning 4-12 weeks after an acute coronary syndrome. Absence of diabetes at baseline was based on medical history, no use of antihyperglycemic medication, and hemoglobin A and serum glucose levels below diagnostic thresholds. Among these patients, incident diabetes after randomization was defined by any diabetes-related adverse event, new use of antihyperglycemic medication, hemoglobin A ≥6.5%, or a combination of at least two measurements of serum glucose ≥7.0 mmol/L (fasting) or ≥11.1 mmol/L (random). 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; < 0.001), and a need to treat 40 patients for 3 years to prevent 1 incident case of diabetes. Considering only those with prediabetes at baseline, the number needed to treat for 3 years to prevent 1 incident case of diabetes was 25. Dalcetrapib also decreased the number of patients who progressed from normoglycemia to prediabetes and increased the number who regressed from diabetes to no diabetes. In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.