Introduction: Additional lipid-lowering therapies are often added to statin drugs in patients with type 2 diabetes (T2D) who fail to achieve target LDL. Our objective was to compare the efficacy and safety of two second-line LDL lowering options: colesevelam (COL) and ezetimibe (EZE) in T2D.
Methods: GOAL-RCT is the first randomized controlled trial comparing COL vs. EZE (NCT02682680). This open-label, randomized, parallel-group, multi-centre trial included patients with T2D with uncontrolled A1c (7 - 10%) and LDL cholesterol (>2 mmol/L or 77.2 mg/dl) - and randomized them to either COL (3.75g daily) or EZE (10 mg daily). T2D medications as well as statin dose were unchanged during the trial. The primary outcome was the proportion of patients achieving A1c ≤7.0% and LDL ≤77.2 mg/dl. Intention to treat analysis was performed for the trial subjects who took at least one dose of the study medication.
Results: GOAL-RCT enrolled 200 subjects with comparable baseline characteristics: mean age 59 ± 10 years, mean A1c 8.0%, mean LDL 97.2 mg/dl with 97% of the subjects on statin drugs. The proportion of patients achieving the composite target of A1c ≤7.0% and LDL ≤77.2 mg/dl in the COL arm was non-inferior to that in the EZE arm (Table 1). A greater proportion of patients in the COL arm achieved the secondary composite endpoint of A1c reduction of ≥0.3% and LDL reduction of ≥10% from baseline (p =0.03). Proportion of patients with goal achievement for A1c ≤ 7.0% was also greater for COL arm compared to EZE (P<0.01). In contrast, a greater proportion of patients taking EZE achieved LDL target of ≤ 77.2 mg/dl compared to COL (P<0.01). The COL arm had a smaller mean reduction in LDL (p<0.01), but a greater reduction in mean A1c (p<0.01), compared to EZE. Adverse effects were minimal and balanced among the trial arms.
Conclusion: Ezetimibe produced greater reductions in LDL cholesterol, whereas colesevelam produced greater reductions in A1c as well as more patients with a composite reduction in A1c and LDL.