Effects of hypolipidemic and hypoglycemic agents on atherogenic small, dense LDL in Type 2 diabetes

Type 2 diabetes is associated with a cluster of inter-related plasma lipid and lipoprotein abnormalities, including reduced HDL-C, a predominance of small, dense LDL and elevated triglycerides. These abnormalities occur even in prediabetes, before blood sugars rise sufficiently in order to confirm a diagnosis of diabetes, and this transition phase incurs important cardiovascular risk. This is the rationale for paying attention to dyslipidemia through the use of the hypolipidemic, rather than hypoglycemic drugs only. A literature search (by Medline and Scopus) was performed. The authors also manually reviewed the references of selected articles for any pertinent material. Beyond the 'quantity' of LDL, several lipid-lowering agents and particularly statins, are only in part beneficial on the 'quality'of LDL, so that their net effect on small, dense LDL is moderate. Among hypoglycemic agents, insulin and metformin have shown a limited role on small, dense LDL, while pioglitazone is more beneficial. The efficacy of incretin-based therapies on LDL subclasses remains to be tested by future studies, considering that preliminary studies have reported significant improvements by these agents on triglycerides and HDL-C plasma concentrations. Beyond hypolipidemic drugs, hypoglycemic agents have been found to be significantly effective in modulating levels of small, dense LDL, towards less atherogenic particles in patients with Type 2 diabetes. This may be linked to the reduction in cardiovascular risk obtained by these agents in this category of high-risk subjects.