Exploratory analysis of RYGB and SG shows variable LDL cholesterol response in patients with obesity and high LDL cholesterol.

This exploratory analysis of a randomized clinical trial (BASALTO) included 30 patients with obesity and high LDL cholesterol. The population was divided into 15 patients receiving Roux-en-Y gastric bypass (RYGB) and 15 patients receiving sleeve gastrectomy (SG). Follow-up assessments occurred at 3 months and 12 months. The primary outcome measured LDL cholesterol response, while secondary outcomes included lipidomic changes, cholesterol absorption patterns, and specific molecular levels.

Results indicated consistent reductions in LDL cholesterol after RYGB, though absolute numbers and effect sizes were not reported. In contrast, LDL cholesterol response after SG demonstrated marked interindividual variability. No significant associations were observed between lipidomic changes and LDL cholesterol after RYGB. However, after SG, monoacylglycerol (16:0, 20:4, 18:1) changes were directly associated with LDL cholesterol at 3 months. Additionally, cholestanol increases were directly associated with LDL cholesterol at 12 months with a pFDR of 0.039, and HexCer 18:0 increases were directly associated with LDL cholesterol at 12 months with a pFDR of 0.031.

Safety and tolerability data, including adverse events, serious adverse events, discontinuations, and specific tolerability metrics, were not reported. The study was limited by its exploratory nature and the lack of significant associations observed after RYGB. The practice relevance suggests that LDL cholesterol reduction after RYGB appears independent of shifts in selected lipids, whereas variability after SG may be partly driven by cholesterol absorption and ceramide-related pathways.

Clinicians should interpret these findings with caution given the exploratory analysis designation. The observed associations after SG indicate potential pathways involving cholesterol absorption and ceramide-related molecules. Further research is needed to confirm these mechanisms and establish definitive causal links before altering clinical management based solely on these preliminary findings.