Efficacy and safety of PCSK9 inhibitors in patients with diabetes: A systematic review and meta-analysis

Abstract

Aims: Individuals with diabetes have increased cardiovascular risk. Although PCSK9 inhibitors bring about a wide reduction in lipids, there is uncertainty about the effects for diabetic patients. We conducted a systematic review and meta-analysis to assess the efficacy and safety of PCSK9 inhibitors for diabetes.

Data synthesis: We performed a meta-analysis comparing treatment with PCSK9 inhibitors versus controls up to July 2022. Primary efficacy endpoints were percentage changes in lipid profile parameters. We used random effects meta-analyses to combine data. Subgroups of diabetic patients (by diabetes type, baseline LDL-C, baseline HbA1c and follow-up time) were also compared. We included 12 RCTs comprising 14,702 patients. Mean reductions in LDL-C were 48.20% (95% CI: 35.23%, 61.17%) in patients with diabetes. Reductions observed with PCSK9 inhibitors were 45.23% (95% CI: 39.43%, 51.02%) for non-HDL-cholesterol, 30.39% (95% CI: 24.61%, 36.17%) for total cholesterol, 11.96% (95% CI: 6.73%, 17.19%) for triglycerides, 27.87% (95% CI: 22.500%, 33.17%) for lipoprotein(a), 42.43% (95% CI: 36.81%, 48.06%) for apolipoprotein B; increases in HDL-C of 5.97% (95% CI: 4.59%, 7.35%) were also observed. There was no significant difference in fasting plasma glucose (FPG) (WMD: 2.02 mg/mL; 95% CI: -1.83, 5.87) and HbA1c (WMD: 1.82%; 95% CI: -0.63, 4.27). Use of a PCSK9 inhibitor was not associated with increased risk of treatment-emergent adverse event (TEAE) (p = 0.542), serious adverse event (SAE) (p = 0.529) and discontinuations due to AEs (p = 0.897).

Conclusions: PCSK9 inhibitor therapy should be considered for all diabetic individuals at high risk of atherosclerotic cardiovascular disease.

Registration code in prospero: CRD42022339785.

Keywords: Cholesterol-lowering therapies; Diabetes; Meta-analysis; PCSK9.