Impact of low-dose quetiapine-use on glycosylated hemoglobin, triglyceride and cholesterol levels

Objective Quetiapine use at standard doses has been associated with hyperglycemia and dyslipidemia. However, whether even frequently prescribed low-dose quetiapine results in significant metabolic disturbances remains unclear. Thus, this study aimed to investigate the association between off-label, low-dose quetiapine and changes in glycosylated hemoglobin (HbA1c) levels/lipid parameters. Methods We identified new users of low-dose quetiapine (<= 50 mg tablets) in Denmark 2008-2018 with measurements of HbA1c, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), or fasting triglycerides (fTG) within 365 days before and after quetiapine initiation. Mixed-effects linear regression models were used to estimate coefficients (beta) with 95% confidence intervals (95%CIs) for change in cardiometabolic parameters after quetiapine initiation. Inverse probability weighting was used to mitigate selection bias. Higher doses of quetiapine (>50 mg) were included in sensitivity analyses. Results Among 106,711 eligible new low-dose quetiapine users (median age = 45 years, females = 55%), low-dose quetiapine initiation was associated with increased fTG (beta = 1.049[95%CI:1.027-1.072]) and decreased HDL-C (beta = 0.982[0.978-0.986]). Although HbA1c did not change significantly and TC and LDL-C even decreased considering all subjects, all three metabolic parameters increased significantly among individuals with normal pre-quetiapine initiation levels. The adverse metabolic effect of quetiapine on HbA1c, TC, LDL-C, and HDL-C was dose-dependent, which was not the case for fTG. Conclusions Low-dose quetiapine was associated with a significant increase in fTG and decreases in HDL-C in all subjects, as well as with significant increases in HbA1c, TC, and LDL-C among those with normal baseline values. The risk of metabolic worsening with quetiapine was dose-dependent, except for fTG.