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4. Dalcetrapib promises risk reduction of new-onset diabetes with coronary heart disease


      Incident type 2 diabetes is common among patients with acute coronary syndrome and is associated with an adverse prognosis. Several studies had revealed that approximately 30% of patients with acute coronary syndrome (ACS) have a prior history of type 2 diabetes, 10% may be diagnosed with diabetes during hospitalization for ACS and 10% may receive the diagnosis of diabetes over the ensuing 5 years. The development of type 2 diabetes carries an increased risk of microvascular and macrovascular complications and is associated with a particularly poor prognosis after ACS. Therefore, there has been deep interest in pharmacologic and nonpharmacologic strategies to reduce incident type 2 diabetes in patients with ACS. A recent research on this aspect had revealed that cholesteryl ester transfer protein (CETP) inhibitor can be promising to reduce incident type 2 diabetes and thus the drug dalcetrapib which belongs to CETP inhibitors.

      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. The criteria also include the absence of diabetes at baseline on the basis of medical history, without use of antihyperglycemic medication, and HbA1c 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, HbA1c ≥6.5%, or a combination of at least two measurements of serum glucose ≥7.0 mmol/L in fasting or ≥11.1 mmol/L random.

      The study results put forth the facts that at baseline, 67% of the trial cohort did not have diabetes. During a median follow-up of 30 months, incident diabetes was identified in 7.6% of the patients assigned to dalcetrapib and in 9.7% assigned to placebo, corresponding to absolute risk reduction of 2.1%, hazard ratio of 0.77 (95% CI 0.68–0.88; P < 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.

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