Dissemin is shutting down on January 1st, 2025

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American Diabetes Association, Diabetes Care, 2(41), p. 364-367, 2017

DOI: 10.2337/dc17-1464

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Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors and Incident Type 2 Diabetes: A Systematic Review and Meta-analysis With Over 96,000 Patient-Years

This paper was not found in any repository, but could be made available legally by the author.
This paper was not found in any repository, but could be made available legally by the author.

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Abstract

OBJECTIVE Like mutations with loss of function in the proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, inhibitors of PCSK9 (PCSK9i) may potentially favor the manifestation of diabetes. RESEARCH DESIGN AND METHODS A meta-analysis of phase 2/3 randomized clinical trials (RCTs) assessed PCSK9i versus placebo in the primary hypercholesterolemia setting. Statins and ezetimibe were used in 98.4% of these studies and balanced between PCSK9i and placebo. We calculated relative risks (RRs) and 95% CIs using random- and fixed-effect models. RESULTS We included 68,123 participants (20 RCTs) with median follow-up of 78 weeks. PCSK9i increased fasting blood glucose (weighted mean difference 1.88 mg/dL [95% CI 0.91–2.68]; I2 = 0%; P < 0.001) and HbA1c (0.032% [0.011–0.050]; I2 = 15.5%; P < 0.001) when compared with placebo. This effect was not sufficient to increase incidence of diabetes (RR 1.04 [0.96–1.13]; I2 = 0%; P = 0.427). Exploratory meta-regression analyses indicated an association between the increased risk of diabetes and the potency (P = 0.029) and duration (P = 0.026) of PCSK9i treatment. CONCLUSIONS In the short term, PCSK9i therapy favors a small but significant increase in plasma glycemia and HbA1c.