Therapy with cholesteryl ester transfer protein (CETP) inhibitors and diabetes risk

Walter Masson (1, 2) , Martín Lobo (1) , Daniel Siniawski (1, 2) , Melina Huerín (1) , Graciela Molinero (1) , Rene Valero (3, 4, 5) , Juan P Nogueira (2, 6)

1 Council of Epidemiology and Cardiovascular Prevention [Buenos Aires, Argentina]
2 Argentine society of lipids [Córdoba, Argentina]
3 NORT - Nutrition, obésité et risque thrombotique
4 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
5 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research
6 Facultad de Ciencias de la Salud [Formosa, Argentina]

BACKGROUND: Cholesteryl ester transfer protein (CETP) inhibitors are a class of drugs that targets the CETP enzyme to significantly increase serum high-density lipoprotein cholesterol (HDL-C) and decrease low-density lipoprotein cholesterol (LDL-C) levels. As HDL-C has potential antidiabetic properties, and the beneficial effects of CETP drugs on glucose homoeostasis have not been sufficiently studied, the aims of this study were: (1) to evaluate the effect of CETP inhibitors on the incidence of diabetes; and (2) to assess the association between CETP inhibitor-induced changes in HDL-C levels and incidence of diabetes. METHODS: A meta-analysis was performed of randomized controlled clinical trials of CETP inhibitor therapy, either alone or combined with other lipid-lowering drugs, reporting data from new cases of diabetes with a minimum of 6 months of follow-up, after searching the PubMed/MEDLINE, Embase and Cochrane Controlled Trials databases. A fixed-effects meta-regression model was then applied. RESULTS: Four eligible trials of CETP inhibitors, involving a total of 73,479 patients, were considered for the analyses, including 960 newly diagnosed cases of diabetes in the CTEP inhibitor group vs 1086 in the placebo group. CETP inhibitor therapy was associated with a significant 12% reduction in incidence of diabetes (OR: 0.88, 95% CI: 0.81-0.96; P=0.005). Assessment of the relationship between on-treatment HDL-C and the effect of CETP inhibitors showed a statistically non-significant trend (Z=-1.13, P=0.26). CONCLUSION: CETP inhibitors reduced the incidence of diabetes. The improvement in glucose metabolism may have been related, at least in part, to the increase in HDL-C concentration. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Mots clés: Cholesteryl ester transfer protein inhibitors; High-density lipoprotein cholesterol; New-onset diabetes; Meta-analysis

Domaines: Endocrinologie et métabolisme; Pharmacologie

Walter Masson, Martín Lobo, Daniel Siniawski, Melina Huerín, Graciela Molinero, et al.. Therapy with cholesteryl ester transfer protein (CETP) inhibitors and diabetes risk. Journal of Diabetes & Metabolism, 2018, 44 (6), epub ahead of print. ⟨10.1016/j.diabet.2018.02.005⟩. ⟨hal-01757621⟩