Rediscovering bile acid sequestrants.
OBJECTIVE
In the recently published The Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) mega-trial, rosuvastatin significantly reduced cardiovascular events at the expense of a small but significant increase in the risk of developing type 2 diabetes. The increased risk of new-onset diabetes was in keeping with a recent meta-analysis which suggested that statins, with the possible exception of pravastatin, marginally increase the risk of developing type 2 diabetes.


METHODS
Although the net effect of rosuvastatin was obviously very positive, we hypothesized that the addition of a bile aid sequestrant to a statin would not only further decrease lipid levels and potentially further decrease cardiovascular events but also protect against the development of diabetes. This is particularly relevant because the bile acid sequestrant, colesevelam, has recently been approved for therapy of diabetes.


RESULTS
Colesevelam like other bile acid sequestrants lowers low-density lipoprotein levels by 16% and C-reactive protein by 22% beyond the reductions that occur with statin therapy alone. Bile acid sequestrants confer lipid-lowering, glucose-lowering, and anti-inflammatory benefits, and have been shown to reduce risk of cardiovascular events.


CONCLUSIONS
Therefore, colesevelam should be the most effective and logical agent to add to a statin in the diabetic and insulin-resistant patient, because in addition to lowering cardiac risk it may prevent the development of diabetes, as well as improving glycaemic control in the established diabetic patient.
Bell
D S H
DS
Southside Endocrinology and University of Alabama Medical School-Birmingham, Alabama, USA.
O'Keefe
James H
JH
D000499:Allylamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D000069472:Colesevelam Hydrochloride; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D004359:Drug Therapy, Combination / Q000379:methods; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D011322:Primary Prevention; D011743:Pyrimidines / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D005464:Fluorobenzenes; D007004:Hypoglycemic Agents; D011743:Pyrimidines; D013449:Sulfonamides; D000499:Allylamine; D000068718:Rosuvastatin Calcium; D000069472:Colesevelam Hydrochloride