Effect of the proprotein convertase subtilisin/kexin type 9 inhibitor evolocumab on glycemia, body weight, and new-onset diabetes mellitus

Journal article

Statin therapy modestly increases new-onset diabetes risk. The effect of PCSK9 inhibition on new-onset diabetes, glycemia and weight remains unclear.We studied the effects of the PCSK9 inhibitor evolocumab on fasting plasma glucose [FPG], glycated hemoglobin (HbA1c), weight and new-onset diabetes mellitus. We pooled 1-year (48-week) data for participants who had completed an evolocumab parent study before entering an open-label extension (OLE) trial. Data were available for 4,802 participants (1,602 on standard of care [SOC]; 3,200 on evolocumab plus SOC) in 2 OLE trials. Evolocumab lowered LDL-cholesterol by approximately 60% compared to SOC alone. Over the first year of the OLE trials, there was no difference in median (Q1, Q3) change in HbA1c (0.1% [–0.1, 0.2] for both SOC and evolocumab plus SOC) and FPG (0.06mmol/L [–0.28, 0.38 mmol/L] for SOC and 0.06mmol/L [–0.28, 0.44 mmol/L] for evolocumab plus SOC). Mean weight change (standard error) at 1 year was –0.1kg (0.2) on SOC compared to 0.3kg (0.1) on evolocumab plus SOC. The exposure-adjusted incidence rate (95% confidence intervals) for new-onset diabetes per 100 patient years was 3.7 (2.9-4.7) on control/SOC alone and 3.9 (3.2-4.6) on evolocumab/evolocumab plus SOC treatment. Glycemic changes observed in 6,430 participants at week 12 in the parent studies were comparable to OLE trial findings. In conclusion, evolocumab therapy has no effect on glucose homeostasis over 1 year of open-label treatment.

Authors: Sattar, N; Toth, P; Blom, D; Koren, M; Soran, H

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: American Journal of Cardiology
• Volume: 120
• Issue: 9
• Pages: 1521-1527
• Publication date: 2017-07-31
• Acceptance date: 2017-07-21
• DOI: 10.1016/j.amjcard.2017.07.047
• EISSN: 1879-1913
• ISSN: 0002-9149
• Keywords: glucose; evolocumab; new-onset diabetes; HbA1c; PCSK9