Abstract
Data were available for more than 550,000 individuals and 51,623 cases of type 2 diabetes. Combined analyses of four independent PCSK9 variants (rs11583680, rs11591147, rs2479409, and rs11206510) scaled to 1 mmol/L lower LDL cholesterol showed associations with increased fasting glucose (0 09 mmol/L, 95% CI 0 02 to 0 15), bodyweight (1 03 kg, 0 24 to 1 82), waist-to-hip ratio (0 006, 0 003 to 0 010), and an odds ratio for type diabetes of 1 29 (1 11 to 1 50). Based on the collected data, we did not identify associations with HbA1c (0 03%, -0 01 to 0 08), fasting insulin (0 00%, -0 06 to 0 07), and BMI (0 11 kg/m2, -0 09 to 0 30). PCSK9 variants associated with lower LDL cholesterol were also associated with circulating higher fasting glucose concentration, bodyweight, and waist-to-hip ratio, and an increased risk of type 2 diabetes. In trials of PCSK9 inhibitor drugs, investigators should carefully assess these safety outcomes and quantify the risks and benefits of PCSK9 inhibitor treatment, as was previously done for statins.