Colesevelam Plus Rosuvastatin 5 mg/Day Versus Rosuvastatin 10 mg/Day Alone on Markers of Insulin Resistance in Patients with Hypercholesterolemia and Impaired Fasting Glucose

Background: Statin use has been associated with adverse effects on insulin sensitivity and the development of new-onset diabetes. Colesevelam exhibits favorable effects on glucose metabolism. It is not known whether the combination of colesevelam plus low-dose statin has different effects on insulin resistance versus higher-dose statin in patients with impaired fasting glucose (IFG) and hypercholesterolemia. Methods: This was a prospective randomized open-label blinded end point (PROBE) study. Forty patients with hypercholesterolemia and IFG were randomized to receive rosuvastatin 5 mg/day plus colesevelam 3.75 g/day (RC, n = 20) or rosuvastatin 10 mg (R, n = 20) for 3 months. The primary end point was the difference in the change of homeostasis model assessment of insulin resistance (HOMA-IR) index between the groups. Results: HOMA-IR index significantly decreased in the RC group (-32%, P = 0.04 vs. baseline) but nonsignificantly increased (+ 15%, P = NS) in the R group. Insulin levels decreased in the RC group (-26%, P = NS) but increased in the R group (+15%, P = NS). Both changes in HOMA-IR and insulin differed significantly between groups (both p < 0.05). Glucose levels decreased in the RC group (-5%, P = NS), whereas they remained unaltered in the R group. Similar reductions in low-density lipoprotein cholesterol were observed in both groups (-45%; P < 0.001 vs. baseline). Triglycerides remained unchanged in the RC group but decreased in the R group (-24%, P < 0.001 vs. baseline and P = 0.02 vs. RC group). Conclusions: The combination of colesevelam with rosuvastatin 5 mg/day may be associated with favorable effects on markers of insulin resistance compared with rosuvastatin 10 mg/day in patients with hypercholesterolemia and IFG. Whether this is associated with less new-onset diabetes remains unknown.