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Effect of proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) monoclonal antibodies on new‐onset diabetes mellitus and glucose metabolism: A systematic review and meta‐analysis
Author(s) -
Cao YeXuan,
Liu HuiHui,
Dong QiuTing,
Li Sha,
Li JianJun
Publication year - 2018
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.13235
Subject(s) - pcsk9 , medicine , alirocumab , meta analysis , kexin , publication bias , diabetes mellitus , type 2 diabetes , subgroup analysis , randomized controlled trial , type 2 diabetes mellitus , gastroenterology , endocrinology , cholesterol , ldl receptor , apolipoprotein b , lipoprotein , apolipoprotein a1
Aims To investigate the effect of two clinically applied proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9‐mAbs) on glycaemia and new‐onset diabetes mellitus (NODM). Materials and Methods PubMed, MEDLINE, Embase, Cochrane databases and ClinicalTrials.gov websites were systematically searched for randomized controlled trials that reported data on fasting plasma glucose (FPG), glycated haemoglobin (HbA1c) or NODM incidence. Risk ratios (RRs) for NODM and mean difference (MD) for FPG and HbA1c with 95% confidence intervals (CIs) were calculated using a fixed‐effect model. Heterogeneity was examined using the I 2 statistic and potential publication bias was assessed using funnel plots and Egger’s test. Results A total of 18 studies including 26 123 participants without diabetes were identified. No significant difference was observed in the PCSK9‐mAb treatment groups in terms of NODM (RR 1.05, 95% CI 0.95‐1.16), FPG (MD 0.00 mmol/L, 95% CI −0.02 to 0.02) or HbA1c (MD 0.00% [0 mmol/L], 95% CI −0.01 to 0.01) compared with control groups. Subgroup (PCSK9‐mAb type, participant characteristics, treatment duration, treatment method and differences in control treatment) and sensitivity analyses did not significantly alter the results. Meta‐regression analyses showed that risk of NODM was not associated with baseline age, baseline body mass index (BMI), proportion of men, treatment duration or percent LDL cholesterol reduction. Conclusions Alirocumab and evolocumab, two types of PCSK9‐mAb approved by the US Food and Drug Administration and the European Medicines Agency, had no significant impact on NODM and glucose homeostasis, regardless of PCSK9‐mAb type, participant characteristics, treatment duration, treatment method and differences in control treatment. Baseline age, BMI, proportion of men, treatment duration, and percent change of LDL cholesterol did not influence diabetes risk.