The effect of CETP inhibitors on new-onset diabetes: a systematic review and meta-analysis

Eur Heart J Cardiovasc Pharmacother. 2022 Sep 3;8(6):622-632. doi: 10.1093/ehjcvp/pvac025.

Abstract

Background: Despite the increasing prevalence of type 2 diabetes mellitus (T2DM), limited pharmacologic options are available for prevention. Cholesteryl ester transfer protein inhibitors (CETPis) have been studied primarily as a therapy to reduce cardiovascular disease, but have also been shown to reduce new-onset diabetes. As new trial data have become available, this meta-analysis examines the effect of CETP inhibitors on new-onset diabetes and related glycaemic measures.

Methods and results: We searched MEDLINE, EMBASE, and Cochrane databases (all articles until 4 March, 2021) for randomised controlled trials (RCT) ≥1-year duration, with at least 500 participants, comparing CETPi to placebo, and that reported data on new-onset diabetes or related glycaemic measures [haemoglobin A1C (HbA1C), fasting plasma glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)]. A fixed effects meta-analysis model was applied to all eligible studies to quantify the effect of CETPi therapy on new-onset diabetes. Four RCTs (n = 75 102) were eligible for quantitative analysis of the effect of CETPi on new-onset diabetes. CETPis were found to significantly decrease the risk of new-onset diabetes by 16% (RR: 0.84; 95% CI: 0.78, 0.91; P < 0.001), with low between-trial heterogeneity (I2 = 4.1%). Glycaemic measures were also significantly improved or trended towards improvement in those with and without diabetes across most trials.

Conclusion: Although RCTs have shown mixed results regarding the impact of CETPi on cardiovascular disease, they have shown a consistent reduction in the risk of new-onset diabetes with CETPi therapy. Future trials of CETPis and potentially other HDL-raising agents should therefore specify new-onset diabetes and reversal of existing T2DM as secondary endpoints.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Blood Glucose
  • Cardiovascular Diseases* / diagnosis
  • Cardiovascular Diseases* / epidemiology
  • Cardiovascular Diseases* / prevention & control
  • Cholesterol Ester Transfer Proteins / therapeutic use
  • Diabetes Mellitus, Type 2* / diagnosis
  • Diabetes Mellitus, Type 2* / drug therapy
  • Diabetes Mellitus, Type 2* / epidemiology
  • Fasting
  • Glycated Hemoglobin / metabolism
  • Humans

Substances

  • Blood Glucose
  • CETP protein, human
  • Cholesterol Ester Transfer Proteins
  • Glycated Hemoglobin A