Emerging lipoprotein-related therapeutics for patients with diabetes

Dyslipidemia is a major risk factor for atherosclerosis in both diabetic and nondiabetic subjects, which is a common cause of morbidity and premature mortality. Based on and supported by favorable outcomes of clinical trials, drugs targeting lipoprotein metabolism are widely used, particularly in developed countries. Drugs to improve lipid levels, in particular to lower low-density lipoprotein (LDL) cholesterol (LDL-C), are commonly used for the primary and secondary prevention of cardiovascular disease. Of the LDL-C-lowering drugs, HMG-CoA reductase inhibitors (“statins”) are particularly effective at reducing cardiovascular disease, both in people with and without diabetes mellitus [1, 2], with more intensive LDL-C lowering being more effective than less intensive LDL-C lowering [3–12]. Statins are effective cardioprotective agents in both type 1 and type 2 diabetes patients [2]

Lipid management in patients with chronic kidney disease.

An increased risk of cardiovascular disease, independent of conventional risk factors, is present even at minor levels of renal impairment and is highest in patients with end-stage renal disease (ESRD) requiring dialysis. Renal dysfunction changes the level, composition and quality of blood lipids in favour of a more atherogenic profile. Patients with advanced chronic kidney disease (CKD) or ESRD have a characteristic lipid pattern of hypertriglyceridaemia and low HDL cholesterol levels but normal LDL cholesterol levels. In the general population, a clear relationship exists between LDL cholesterol and major atherosclerotic events. However, in patients with ESRD, LDL cholesterol shows a negative association with these outcomes at below average LDL cholesterol levels and a flat or weakly positive association with mortality at higher LDL cholesterol levels. Overall, the available data suggest that lowering of LDL cholesterol is beneficial for prevention of major atherosclerotic events in patients with CKD and in kidney transplant recipients but is not beneficial in patients requiring dialysis. The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in CKD provides simple recommendations for the management of dyslipidaemia in patients with CKD and ESRD. However, emerging data and novel lipid-lowering therapies warrant some reappraisal of these recommendations