Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 32419478 · doi:10.1177/1074248420924983
What was done
The authors conducted a systematic review and random-effects meta-analysis searching PubMed, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for double-blind randomized controlled trials evaluating PCSK9 inhibitors or ezetimibe. Inclusion criteria required ≥100 patients per treatment arm, follow-up of ≥52 weeks, and a double-blind design. Exclusion criteria included patients with previously diagnosed diabetes, nonrandomized trials, open-label designs, and crossover trials. The primary outcome was incident diabetes cases. Heterogeneity was evaluated using the I² parameter and Q statistic.
What was found
Eleven trials were analyzed across two drug classes: - PCSK9 inhibitors (8 trials, n = 52,214): Incident diabetes did not differ between treatment and control groups (risk ratio [RR] = 0.99, 95% CI = 0.92–1.07, P = .87). - Ezetimibe (3 trials, n = 20,084): Incident diabetes did not differ between treatment and control groups (RR = 1.05, 95% CI = 0.95–1.15, P = .37).
Why it matters
Unlike statins, which are associated with an increased risk of incident diabetes, adding PCSK9 inhibitors or ezetimibe to lipid-lowering therapy does not appear to increase diabetes risk.
Limits
The analysis relies on aggregate study-level data rather than individual participant data. The minimum follow-up was 52 weeks, which may be insufficient to detect very long-term metabolic effects. Only 3 trials were available for ezetimibe, providing a smaller evidence base than that for PCSK9 inhibitors.
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