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.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 29377473 · doi:10.1111/dom.13235
What was done
A systematic review and meta-analysis of randomized controlled trials searched PubMed, MEDLINE, Embase, Cochrane databases, and ClinicalTrials.gov for studies evaluating PCSK9 monoclonal antibodies (alirocumab and evolocumab) on fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), or new-onset diabetes mellitus (NODM). Pooled risk ratios (RRs) and mean differences (MDs) were calculated with 95% confidence intervals using fixed-effect models. Subgroup, sensitivity, and meta-regression analyses were conducted.
What was found
Across 18 RCTs encompassing 26,123 participants without baseline diabetes, PCSK9-mAb therapy showed no significant difference compared with controls for 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%, 95% CI -0.01 to 0.01). Subgroup and sensitivity analyses did not alter findings. Meta-regression showed no link between NODM risk and baseline age, BMI, sex distribution, treatment duration, or percent LDL cholesterol reduction.
Why it matters
Unlike statin therapy, which carries a recognized modest risk of incident diabetes, these findings provide reassurance that short- to medium-term PCSK9 monoclonal antibody use does not disrupt glucose homeostasis or increase diabetes incidence.
Limits
The analysis relies on aggregate study-level data rather than individual participant data. The abstract does not specify the maximum or median trial follow-up length, leaving long-term glycemic effects beyond typical clinical trial durations unmeasured.
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