Goal achievement of A1C and LDL in a Randomized Trial Comparing Colesevelam vs. Ezetimibe: GOAL-RCT.

AIMS: To compare the efficacy and safety of colesevelam and ezetimibe as second-line LDL lowering options in type 2 diabetes (T2D). MATERIALS AND METHODS: GOAL-RCT is a 24-week, open label, randomized, pragmatic clinical trial. Subjects with T2D with uncontrolled A1C (7.1-10%) and LDL-c (>2.0 mmol/L) were randomized 1:1 to colesevelam 3.75 g or ezetimibe 10 mg daily. The primary composite outcome was the proportion of participants achieving LDL-c target ≤2.0 mmol/L and A1C target ≤7.0%. Intention to treat analysis was performed. RESULTS: 200 subjects were enrolled: mean age 59 ± 10 years; mean A1C 8.0%; mean LDL-c 2.5 mmol/L; 97% on statin therapy. The primary composite outcome was achieved by similar proportion of participants with colesevelam (14.6%) and ezetimibe (10.5%), pnon-inferiority  < 0.001, psuperiority  = 0.41. LDL-c reduction from baseline was less with colesevelam compared to ezetimibe (14.0% vs. 23.2%, p < 0.01), as was the proportion of subjects achieving LDL-c target ≤2.0 mmol/L (47.6% and 67.0%, respectively; p = 0.007). Mean A1C was reduced with colesevelam (-0.26 ± 0.10%), while no change was observed with ezetimibe (difference p = 0.06). Adverse events (AE) and discontinuation rates were higher for colesevelam (20.2% and 31.1%) compared to ezetimibe (7.2% and 6.2%), respectively. CONCLUSIONS: Among subjects with T2D, the initiation of colesevelam or ezetimibe led to similar achievement of primary composite outcome (LDL-c and A1c within target), with ezetimibe recording a greater LDL-c reduction and better toleratability than colesevelam. CLINICAL TRIAL REGISTRATION: NCT02682680.