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

Diabetes Care. 2020 May;43(5):1077-1084. doi: 10.2337/dc19-2204. Epub 2020 Mar 6.

Abstract

Objective: 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.

Research design and methods: 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 A1c 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 A1c ≥6.5%, or a combination of at least two measurements of serum glucose ≥7.0 mmol/L (fasting) or ≥11.1 mmol/L (random).

Results: 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; 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.

Conclusions: In patients with a recent acute coronary syndrome, incident diabetes is common and is reduced substantially by treatment with dalcetrapib.

Trial registration: ClinicalTrials.gov NCT00658515.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / complications
  • Acute Coronary Syndrome / drug therapy
  • Acute Coronary Syndrome / epidemiology
  • Aged
  • Amides / therapeutic use*
  • Anticholesteremic Agents / therapeutic use
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Cohort Studies
  • Coronary Disease / complications
  • Coronary Disease / drug therapy*
  • Coronary Disease / epidemiology
  • Diabetes Mellitus, Type 2 / epidemiology
  • Diabetes Mellitus, Type 2 / prevention & control*
  • Esters / therapeutic use*
  • Female
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Prediabetic State / complications
  • Prediabetic State / drug therapy
  • Prediabetic State / epidemiology
  • Prediabetic State / pathology
  • Risk Factors
  • Risk Reduction Behavior
  • Sulfhydryl Compounds / therapeutic use*

Substances

  • Amides
  • Anticholesteremic Agents
  • Blood Glucose
  • Esters
  • Sulfhydryl Compounds
  • dalcetrapib

Associated data

  • ClinicalTrials.gov/NCT00658515