Skip to main content

01-28-2017 | Dyslipidemia | Review | Article

Treatment of Dyslipidemias to Prevent Cardiovascular Disease in Patients with Type 2 Diabetes

Journal: Current Cardiology Reports

Authors: Maryam Khavandi, Francisco Duarte, Henry N. Ginsberg, Gissette Reyes-Soffer

Publisher: Springer US


Purpose of Review

Current preventive and treatment guidelines for type 2 diabetes have failed to decrease the incidence of comorbidities, such as dyslipidemia and ultimately heart disease. The goal of this review is to describe the physiological and metabolic lipid alterations that develop in patients with type 2 diabetes mellitus. Questions addressed include the differences in lipid and lipoprotein metabolism that characterize the dyslipidemia of insulin resistance and type 2 diabetes mellitus. We also examine the relevance of the new AHA/ADA treatment guidelines to dyslipidemic individuals.

Recent Findings

In this review, we provide an update on the pathophysiology of diabetic dyslipidemia, including the role of several apolipoproteins such as apoC-III. We also point to new studies and new agents for the treatment of individuals with type 2 diabetes mellitus who need lipid therapies.


Type 2 diabetes mellitus causes cardiovascular disease via several pathways, including dyslipidemia characterized by increased plasma levels of apoB-lipoproteins and triglycerides, and low plasma concentrations of HDL cholesterol. Treatments to normalize the dyslipidemia and reduce the risk for cardiovascular events include the following: lifestyle and medication, particularly statins, and if necessary, ezetimibe, to significantly lower LDL cholesterol. Other treatments, more focused on triglycerides and HDL cholesterol, are less well supported by randomized clinical trials and should be used on an individual basis. Newer agents, particularly the PCSK9 inhibitors, show a great promise for even greater lowering of LDL cholesterol, but we await the results of ongoing clinical trials.
Geiss LS, Wang J, Cheng YJ, et al. Prevalence and incidence trends for diagnosed diabetes among adults aged 20 to 79 years, United States, 1980-2012. JAMA. 2014;312(12):1218–26. PubMedCrossRef
National Diabetes Statistics Report: estimates of diabetes and its burden in the United States, 2014. Centers for Disease Control and Prevention 2014.
World Health Organization. Cardiovascular diseases (CVDs). http://​www.​who.​int/​mediacentre/​factsheets/​fs317/​en/​
Boden WE, Probstfield JL, Anderson T, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67. PubMedCrossRef
Gotto Jr AM, Pownall HJ, Havel RJ. Introduction to the plasma lipoproteins. Methods Enzymol. 1986;128:3–41. PubMedCrossRef
Ginsberg HN. Lipoprotein physiology. Endocrinol Metab Clin N Am. 1998;27(3):503–19. CrossRef
Lamarche B, Couture P. Dietary fatty acids, dietary patterns, and lipoprotein metabolism. Curr Opin Lipidol. 2016;26(1):42–7. CrossRef
Ginsberg HN, Fisher EA. The ever-expanding role of degradation in the regulation of apolipoprotein B metabolism. J Lipid Res. 2009;50(Suppl):S162–6. PubMedPubMedCentral
Tomkin GH, Owens D. Abnormalities in Apo B-containing lipoproteins in diabetes and atherosclerosis. Diabetes Metab Res Rev. 2001;17:27–43. PubMedCrossRef
Havel RJ. Lipid transport function of lipoproteins in blood plasma. Am J Phys. 1987;253:E1–5.
de Man FH, Cabezas MC, Van Barlingen HHJJ, Erkelens DW, De Bruin TWA. Triglyceride-rich lipoproteins in non-insulin dependent diabetes mellitus:post-prandial metabolism and relation to premature atherosclerosis. Eur J Clin Investig. 1996;26:89–108. CrossRef
Goldberg IJ. Clinical review 124, diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab. 2001;86:965–71. PubMedCrossRef
Mahley RW, Ji ZS. Remnant lipoprotein metabolism: key pathways involving cell-surface heparan sulfate proteoglycans and apolipoprotein. J Lipid Res. 1999;40:1–16. PubMed
Phillips C, Bennett A, Anderton K. Intestinal rather than hepatic microsomal triglyceride transfer protein as a cause of postprandial dyslipidemia in diabetes. Metabolism. 2002;51:847–52. PubMedCrossRef
Phillips C, Owens D, Collins P, Tomkin GH. Microsomal triglyceride transfer protein: does insulin resistance play a role in the regulation of chylomicron assembly? Atherosclerosis. 2002;160:355–60. PubMedCrossRef
Haidari M, Leung N, Mahbub F, et al. Fasting and postprandial overproduction of intestinally derived lipoproteins in an animal model of insulin resistance. J Biol Chem. 2002;277(35):31646–55. PubMedCrossRef
Dressel U, Allen TL, Pippal JB, Rohde PR, Lau P, Muscat GEO. The peroxisome proliferator-activated receptor β/δ agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells. Mol Endocrinol. 2003;17:2477–93. PubMedCrossRef
Xiao C, Dash S, Morgantini C, Adeli K, Lewis GF. Gut peptides are novel regulators of intestinal lipoprotein secretion: experimental and pharmacological manipulation of lipoprotein metabolism. Diabetes. 2015;64(7):2310–8. PubMedCrossRef
Adeli K, Lewis GF. Intestinal lipoprotein overproduction in insulin-resistant states. Curr Opin Lipidol. 2008;19:221–8. PubMedCrossRef
Brunzell JD. Familial lipoprotein lipase deficiency. SourceGeneReviews 2015.
Cohn JS, Patterson BW, Uffelman KD, Davignon J, Steiner G. Rate of production of plasma and very-low-density lipoprotein (VLDL) apolipoprotein C-III is strongly related to the concentration and level of production of VLDL triglyceride in male subjects with different body weights and levels of insulin sensitivity. Journal of Clinical Endocrinology & Metabolism. 2004;89:3949–55. CrossRef
Nagashima K, Lopez C, Donovan D, et al. Effects of the PPAR agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus. JCI. 2005;115:1323–32. PubMedPubMedCentralCrossRef
Ginsberg HN, Zhang Y-L, Hernandez-Ono A. A metabolic syndrome: focus on dyslipidemia. Obesity. 2006;14(Suppl):41S–9S. PubMedCrossRef
Zhang Y-L, Hernandez-Ono A, Ko C, Yasunaga K, Huang L-S, Ginsberg HN. Regulation of hepatic apolipoprotein B-lipoprotein assembly and secretion by the availability of fatty acids 1: differential effects of delivering fatty acids via albumin or remnant-like emulsion particles. J Biol Chem. 2004;279:19362–74. PubMedCrossRef
Lewis GF, Uffelman KD, Szeto LW, Weller B, Steiner G. Interaction between free fatty acids and insulin in the acute control of very low density lipoprotein production in humans. J Clin Invest. 1995;95:158–66. PubMedPubMedCentralCrossRef
Cooper AD. Hepatic uptake of chylomicron remnants. J Lipid Res. 1997;38(11):2173–92. PubMed
Wu X, Sakata N, Dixon JL, Ginsberg HN. Exogenous VLDL stimulates apolipoprotein B from HepG2 cells by both pre- and post-translational mechanisms. J Lipid Res. 1994;35:1200–10. PubMed
Grimaldi PA, Teboul L, Inadera H, Gaillard D, Amri E-Z. Trans-differentiation of myoblasts to adipoblasts: triggering effects of fatty acids and thiazolidinediones. Prostaglandins Leukot Essent Fatty Acids. 1997;57:71–5. PubMedCrossRef
Melish J, Le NA, Ginsberg H, Steinberg D, Brown WV. Dissociation of apoprotein B and triglyceride production in very-low-density lipoproteins. Am J Phys. 1980;239(5):E354–62.
Ma W, Wu JH, Wang Q, et al. Prospective association of fatty acids in the de novo lipogenesis pathway with risk of type 2 diabetes: the Cardiovascular Health Study. Am J Clin Nutr. 2015;101(1):153–63. PubMedCrossRef
Adiels M, Boren J, Caslake MJ, et al. Overproduction of VDLD1 driven by hyperglycemia is a dominant feature of diabetic dyslipidemia. Arterioscler Thromb Vasc Biol. 2005;25:1697–703. PubMedCrossRef
Keeny SJ, Aubert RE, Geiss LS. Prevalence and incidence of insulin-dependent diabetes in America. NIH. National Institute of Health 1995.
Adiels M, Olofsson SO, Taskinen MR, Boren J. Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome. Artheroscler Thromb Vasc Biol. 2008;28:1225–36. CrossRef
Sharma V, Forte TM, Ryan RO. Influence of apolipoprotein AV on the metabolic fate of triacylglycerol 1. Curr Opin Lipidol. 2013;24(2):153–9. PubMedPubMedCentralCrossRef
Robciuc MR, Maranghi M, Lahikainen A, et al. Angptl3 deficiency is associated with increased insulin sensitivity, lipoprotein lipase activity, and decreased serum free fatty acids. Arterioscler Thromb Vasc Biol. 2013;33(7):1706–13. PubMedCrossRef
Kurra S, Ballantyne CM. Special patient populations: diabetes and metabolic syndrome. In Clinical lipidology: a companion to braunwald's heart disease. Elsevier Health Sciences 2009;443–462.
Berneis KK, Krauss RM. Metabolic origins and clinical significance of the LDL heterogeneity. J Lipid Res. 2009;43:1363–79. CrossRef
Mello AP, da Silva IT, Abdalla DS, Damasceno NR. Electronegative low-density lipoprotein: origin and impact on health and disease. Atherosclerosis. 2011;215:257–65. PubMedCrossRef
Rizzo M, Berneis K. Low-density lipoprotein size and cardiovascular risk assessment. QJM. 2006;99:1–14. PubMedCrossRef
Timmins JM, Lee JY, Boudyguina E, et al. Targeted inactivation of hepatic Abca1 causes profound hypoalphalipoproteinemia and kidney hypercatabolism of apoA-1. J Clin Invest. 2005;115:1333–42. PubMedPubMedCentralCrossRef
Chahil TJ, Ginsberg HN. Diabetic dyslipidemia. Endocrinol Metab Clin N Am. 2006;35:491–510. CrossRef
Lewis GF, Radar DJ. New insights into the regulation of HDL. Metabolism and reverse cholesterol transport. Circ Res. 2005;96:1221–32. PubMedCrossRef
Borggreve SE, De Vries R, Dullaart RP. Alterations in high-density lipoprotein metabolism and reverse cholesterol transport in insulin resistance and type 2 diabetes mellitus: role of lipolytic enzymes, lecithin: cholesterol acyltransferase and lipid transfer proteins. Eur J Clin Investig. 2003;33:1051–69. CrossRef
Horowitz BS, Goldberg IJ, Merab J, Vanni T, Ramakrishnan R, Ginsberg HN. Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A-I in subjects with low levels of high density lipoprotein cholesterol. J Clin Invest. 1993;91:1743–52. PubMedPubMedCentralCrossRef
• Xiao C, Dash S, Morgantini C, Hegele RA, Lewis GF. Pharmacological targeting of the atherogenic dyslipidemia complex: the next frontier in CVD prevention beyond lowering LDL cholesterol. Diabetes. 2016;65(7):1767–78. A thourough desciption on the regulatory effect of GLP-1 and GLP-2 on intestinal lipoprotein secretion and postprandial lipemia PubMedCrossRef
Brinton EA, Eiseberg S, Breslow JL. Human HDL cholesterol levels are determined by apoA-I fractional catabolic rate, which correlates inversely with estimate of HDL particle size. Arterioscler Thromb. 1994;14:707–20. PubMedCrossRef
Liu J, Hernandez-Ono A, Graham MJ, Galton VA, Ginsberg HN. Type 1 deiodinase regulates ApoA-I gene expression and ApoA-I synthesis independent of thyroid hormone signaling. Arterioscler Thromb Vasc Biol. 2016;36(7):1356–66. PubMedCrossRef
Riemens S, van Tol A, Sluiter W, Dullaart R. Elevated plasma cholesteryl ester transfer in NIDDM: relationships with apolipoprotein B-containing lipoproteins and phospholipid transfer protein. Atherosclerosis. 1998;140:71–9. PubMedCrossRef
Deeb SS, Zambon A, Carr MC. Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet. J Lipid Res. 2003;44:1279–86. PubMedCrossRef
• Low Wang CC, Hess CN, Hiatt WR, Goldfine AB. Clinical update: cardiovascular disease in diabetes mellitus: atherosclerotic cardiovascular disease and heart failure in type 2 diabetes mellitus—mechanisms, management, and clinical considerations. Circulation. 2016;133(24):2459–502. This review points out to the mechanisms, history, controversies, and pharmacological agents for cardiovascular management in the patient with diabetes mellitus PubMedCrossRef
Stone NJ, Robinson J, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2013.
Drozda Jr JP, Ferguson Jr TB, Jneid H, et al. 2015 ACC/AHA focused update of secondary prevention lipid performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures. J Am Coll Cardiol. 2016;67(5):558–87. PubMedCrossRef
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) developed with the special contribution of the European Assocciation for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis 53.
Ryden L, Standl E, Bartnik M, for the Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD). Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. Eur Heart J. 2007;28:88–136. PubMedCrossRef
Pavlovic J, Greenland P, Deckers JW et al. Comparison of ACC/AHA and ESC guideline recommendations following trial evidence for statin use in primary prevention of cardiovascular disease: results from the population-based Rotterdam Study. JAMA Cardiol 2016.
Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2016;346(6):393–403.
American Diabetes Association. Standards of medical care in diabetes—2016. Diabetes Care 2016;39(suppl 1).
Siegel RD, Cupples A, Schaefer EJ, Wilson PWF. Lipoproteins, apolipoproteins, and low-density lipoprotein size among diabetics in the Framingham Offspring Study. Metabolism. 1996;45(10):1267–72. PubMedCrossRef
Howard BV, Cowan LD, Go O, Welty TK, Robbins DC, Lee ET. Adverse effects of diabetes on multiple cardiovascular disease risk factors in women. Diabetes Care. 1998;21:1258–65. PubMedCrossRef
Juutilainen A, Kortelainen S, Lehto S, et al. Gender difference in the impact of type 2 diabetes on coronary heart disease risk. Diabetes Care. 2004;27:2898–904. PubMedCrossRef
Haffner SM, Miettinen H, Stern MP. Relatively more atherogenic coronary heart disease risk factors in prediabetic women than in prediabetic men. Diabetologia. 1997;40:711–7. PubMedCrossRef
• PD Rosenblit. Common medications used by patients with type 2 diabetes mellitus: what are their effects on the lipid profile? Cardiovasc Diabetol 2016;15(95). An overview on type 2 diabetes mellitus treatment effects on lipid profile and their overall potential impact on ASCVD risk.
Choe EY, Cho Y, Choi Y, et al. The effect of DPP-4 inhibitors on metabolic parameters in patients with type 2 diabetes. Diabetes Metab J. 2014;38(3):211–9. PubMedPubMedCentralCrossRef
Harris KB, McCarty DJ. Efficacy and tolerability of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus. Ther Adv Endocrinol Metab. 2015;6(1):3–18. PubMedPubMedCentralCrossRef
Zaccardi F, Webb DR, Htike ZZ, Youssef D, Khunti K, Davies MJ. Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis. Diabetes Obes Metab. 2016;18(8):783–94. PubMedCrossRef
Rosenthal N, Meininger G, Ways K, et al. Canagliflozin: a sodium glucose co-transporter 2 inhibitor for the treatment of type 2 diabetes mellitus. Ann N Y Acad Sci. 2016;1358:28–43. CrossRef
Matthaei S, Bowering K, Rohwedder K, Grohl A, Parikh S, Study 05 Group. Dapagliflozin improves glycemic control and reduces body weight as add-on therapy to metformin plus sulfonylurea: a 24-week randomized, double-blind clinical trial. Diabetes Care. 2015;38(3):365–72. PubMedCrossRef
Rosenstock J, Rigby SP, Ford DM, Tao B, Chou HS. The glucose and lipid effects of colesevelam as monotherapy in drug-naïve type 2 diabetes. Horm Metab Res. 2014;46(5):348–53. PubMed
Monami M, Vitale V, Ambrosio ML, et al. Effects on lipid profile of dipeptidyl peptidase 4 inhibitors, pioglitazone, acarbose, and sulfonylureas: meta-analysis of placebo-controlled trials. Adv Ther. 2012;29(9):736–46. PubMedCrossRef
Doggrell SA. Clinical trials with thiazolidinediones in subjects with type 2 diabetes—is pioglitazone any different from rosiglitazone? Expert Opin Pharmacother. 2008;9(3):405–20. PubMedCrossRef
Chiquette E, Ramirez G, Defronzo R. A meta-analysis comparing the effect of thiazolidinediones on cardiovascular risk factors. Arch Intern Med. 2004;164(19):2097–104. PubMedCrossRef
Yau H, Rivera K, Lomonaco R, Cusi K. The future of thiazolidinedione therapy in the management of type 2 diabetes mellitus. Curr Diab Rep. 2013;13(3):329–41. PubMedCrossRef
Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm—2016 executive summary. Endocr Pract. 2016;22(1):84–113. PubMedCrossRef
Palmer SC, Mavridis D, Nicolucci A, et al. Comparison of clinical outcomes and adverse events associated with glucose-lowering drugs in patients with type 2 diabetes: a meta-analysis. JAMA. 2016;316(3):313–24. PubMedCrossRef
Scheen AJ. SGLT2 inhibitors: benefit/risk balance. Curr Diab Rep. 2016;16(10):92. PubMedCrossRef
Wilding JP, Rajeev SP, DeFronzo RA. Positioning SGLT2 inhibitors/incretin-based therapies in the treatment algorithm. Diabetes Care. 2016;39(supp2:S):154–64. CrossRef
Kernan WA, Viscoli CM, Furie KL, Winder TR, IRIS Trial Investigators. Pioglitazone after ischemic stroke or transient ischemic attack. NE J Med. 2016;374(14):1321–31. CrossRef
Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373(22):2117–28. PubMedCrossRef
Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375(4):311–22. PubMedPubMedCentralCrossRef
Marso SP, Bain SC, Consoli A, Eliaschewitz FG. SUSTAIN-6 investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. NE J Med 2016.
Mooradian AD. Cardiovascular disease in type 2 diabetes mellitus: current management guidelines. Arch Intern Med. 2003;163(1):33–40. PubMedCrossRef
Warraich HJ, Wong ND, Rana JS. Role for combination therapy in diabetic dyslipidemia. Curr Cardiol Rep. 2015;17(5):32. PubMedCrossRef
Kearney PM, Blackwell L, Collins R, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371(9607):117–25. PubMedCrossRef
National Cholesterol Education Program. Third report of the expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III). JAMA. 2001;285(19):2486–97. CrossRef
American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2007;30(Suppl):S4–S41. CrossRef
Ginsberg HN. Efficacy and mechanism of action of statins in the treatment of diabetic dyslipidemia. J Clin Endocrinol Metab. 2006;91:383–92. PubMedCrossRef
Buse JB, Ginsberg HN, Bakris GL, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus. A scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care. 2007;30:162–72. PubMedCrossRef
• Collins R, Armitage J, Parish S, HPSCG. MRC/BHF heart protection study of cholesterol-lowering with simvastatin in 5,963 people with diabetes. Lancet. 2005;361:2005–16. A randomized trial of the effect of simvastatin vs placebo in patients with diabetes that provides direct evidence that cholesterol-lowering therapy is beneficial for these people even if they do not show manifestation of coronary disease or high cholesterol concentrations
• Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387–97. A comparison of the combination of simvastatin and ezetimibe with simvastatin and placebo on the cardiovascular outcome in patients with acute coronary syndromes PubMedCrossRef
Frick MH, Elo MO, Haapa K, et al. Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. NE J Med. 1987;317:1237–45. CrossRef
Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. 1999;341(6):410–8. PubMedCrossRef
Bezafibrate Infarction Prevention (BIP) study1. Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease. Bezafibrate Infarction Prevention (BIP) study. Circulation. 2000;102(1):21–7. CrossRef
•• Keech A, Simes RJ, Barter P. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005;366:1849–61. A control trial study of individuals with type 2 diabetes mellitus not on statin therapy, randomized to take fenofibrate vs placebo for 5 years to assess the effect of fenofibrate on cardiovascular disease events in these patients PubMedCrossRef
Scott R, O'Brien R, Fulcher G, et al. Effects of fenofibrate treatment on cardiovascular disease risk in 9,795 individuals with type 2 diabetes and various components of the metabolic syndrome: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study. Diabetes Care. 2009;32:493–8. PubMedPubMedCentralCrossRef
Anderson RT, Narayan KM, Feeney P, et al. Effect of intensive glycemic lowering on health-related quality of life in type 2 diabetes: ACCORD trial. Diabetes Care. 2011;34(4):807–12. PubMedPubMedCentralCrossRef
Accord Study Group, Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1575–85. CrossRef
Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563–74. PubMedCrossRef
Landray MJ, Haynes R, Hopewell JC, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12. PubMedCrossRef
Mann CJ, Yen FT, Grant AM, Bihan BE. Mechanisms of plasma cholesteryl ester transport in hypertriglyceridemia. J Clin Invest. 1991;88:2059–66. PubMedPubMedCentralCrossRef
Tall AR, Granot E, Tabas I, et al. Accelerated transfer of cholesteryl esters in dyslipidemic plasma: role of cholesteryl ester transfer protein. J Clin Invest. 1987;79:1217–25. PubMedPubMedCentralCrossRef
Deckelbaum RJ, Granot E, Oschry Y, Rose L, Eisenberg S. Plasma triglyceride determines structure-composition in low and high density lipoproteins. Arteriosclerosis. 1984;4:225–31. PubMedCrossRef
•• Reyes-Soffer G, Millar JS, Ngai C et al. Cholesteryl ester transfer protein inhibition with anacetrapib decreases fractional clearance rates of high-density lipoprotein apolipoprotein A-I and plasma cholesteryl ester transfer protein. Artheroscler Thromb Vasc Biol 2016;115. A study on the effects of CETP inhibition on the kinetics of CETP in humans.
Barter PJ, Caulfield M, Eriksson M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109–22. PubMedCrossRef
Schwartz GG, Olsson AG, Abt M, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. NE J Med. 2012;367(22):2089–99. CrossRef
•• Nicholls SJ, Lincoff AM, Barter PJ, et al. Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: rationale and design of the ACCELERATE trial. Am Heart J. 2015;170(6):1061–9. A contol trial study on 12,092 individual with high-risk vascular disease, randomized to take evacetrapib or placebo in addition to standard medical therapy and to acess its effect on the cardiovascular morbidity and mortality PubMedCrossRef
Rader DJ, Tall AR. The not-so-simple HDL story: is it time to revise the HDL cholesterol hypothesis? Nat Med. 2012;18(9):1344–6. PubMedCrossRef
McKenney JM, Koren MJ, Kereiakes DJ, Hanotin C, Ferrand AC, Stein EA. Safety and efficacy of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease, SAR236553/REGN727, in patients with primary hypercholesterolemia receiving ongoing stable atorvastatin therapy. J Am Coll Cardiol. 2012;59(25):2344–53. PubMedCrossRef
•• Navarese EP, Kolodziejczak M, Schulze V, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis. Ann Intern Med. 2015;163(1):40–51. A phase 3 randomized controlled trial to compare treatment of hypercholesterolemia with and without PCSK9 antibodies which has proven PCSK9 inhibitors to be safe and effective for adults with dyslipidemia PubMedCrossRef
• Robinson JG, Farnier M, Krempf M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489–99. A randomized trial involving 2341 patients at high risk for cardiovascular events and at maximum dose of statin randomly assigned to receive alirocumab over a period of 78 weeks PubMedCrossRef
• Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500–9. This study points to the long-term effect of evolocumab plus standard therapy, as compared with standard therapy alone on reducing LDL cholesterol levels and the incidence of cardiovascular events PubMedCrossRef
• Yang X, Lee SR, Choi YS, et al. Reduction in lipoprotein-associated apoC-III levels following volanesorsen therapy: phase 2 randomized trial results. J Lipid Res. 2016;57(4):706–13. A study on the effects of volanesorsen (an antisense drug that targets apoC3 mRNA ) vs placebo in patients with hypertriglyceridemia PubMedCrossRef
Gutierrez MJ, Rosenberg NL, Macdougall DE, et al. Efficacy and safety of ETC-1002, a novel investigational low-density lipoprotein-cholesterol-lowering therapy for the treatment of patients with hypercholesterolemia and type 2 diabetes mellitus. Arterioscler Thromb Vasc Biol. 2014;34(3):676–83. PubMedCrossRef
Jani RH, Pai V, Jha P, et al. A multicenter, prospective, randomized, double-blind study to evaluate the safety and efficacy of Saroglitazar 2 and 4 mg compared with placebo in type 2 diabetes mellitus patients having hypertriglyceridemia not controlled with atorvastatin therapy (PRESS VI). Diabetes Technol Ther. 2014;16(2):63–71. PubMedPubMedCentralCrossRef
•• Look AHEAD Research Group. Association of the magnitude of weight loss and changes in physical fitness with long-term cardiovascular disease outcomes in overweight or obese people with type 2 diabetes: a post-hoc analysis of the Look AHEAD randomised clinical trial. Lancet Diabetes Endocrinol 2016. This study points to the association between weight loss and the incidence of cardiovascular disease in people with type 2 diabetes from the LOOK AHEAD study after ~10-year follow-up.
Szalat A, Durst R, Leitersdorf E. Managing dyslipidaemia in type 2 diabetes mellitus. Best Pract Res Clin Endocrinol Metab. 2016;30(3):431–44. PubMedCrossRef

Be confident that your patient care is up to date

Medicine Matters is being incorporated into Springer Medicine, our new medical education platform. 

Alongside the news coverage and expert commentary you have come to expect from Medicine Matters diabetes, Springer Medicine's complimentary membership also provides access to articles from renowned journals and a broad range of Continuing Medical Education programs. Create your free account »