Statin Treatment, New-Onset Diabetes, and Other Adverse Effects: A Systematic Review

  • Casper N. BangEmail author
  • Peter M. Okin
Diabetes and Cardiovascular Disease (S Malik, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Diabetes and Cardiovascular Disease


Statin treatment prevents cardiovascular diseases probably beyond their lipid-lowering effect. Increasing evidence suggests that statins might increase the risk of new-onset diabetes; however, diabetes is known to increase the risk of cardiovascular diseases. The majority of the literature suggests an increased risk of new-onset diabetes in patients treated with statins in a number of different settings and that the risk appears greatest among the more potent statins. Furthermore, a dose-response curve has been shown between statin treatment and the development of diabetes. Possible mechanisms include muscle insulin resistance, lower expression of GLUT-4 in adipocytes impairing glucose tolerance and suppression of glucose-induced elevation of intracellular Ca2+ level. However, other side effects have been reported such as increased risk of myotoxicity, increased liver enzymes, cataracts, mood disorders, dementias, hemorrhagic stroke and peripheral neuropathy, which should maybe be added to the increased risk of new-onset diabetes, when considering the risk- benefit ratio of statin treatment.


New-onset diabetes Statin treatment Review Cardiovascular prevention Adverse effects 


Compliance with Ethics Guidelines

Conflict of Interest

Casper N. Bang and Peter M. Okin declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. 1.
    Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78.PubMedCrossRefGoogle Scholar
  2. 2.
    Bang CN, Gislason GH, Greve AM, Torp-Pedersen C, Kober L, Wachtell K. Statins reduce new-onset atrial fibrillation in a first-time myocardial infarction population: a nationwide propensity score-matched study. Eur J Prev Cardiol 2012. doi: 10.1177/2047487312462804.
  3. 3.••
    Preiss D, Seshasai SR, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA. 2011;305:2556–64. This meta-analysis provides a great overview on the subject and shows intensive statin treatment is more likely to produce new-onset diabetes for every cardiovascular event prevented.PubMedCrossRefGoogle Scholar
  4. 4.
    Hippisley-Cox J, Coupland C. Unintended effects of statins in men and women in England and Wales: population based cohort study using the QResearch database. BMJ. 2010;340:c2197.PubMedCentralPubMedCrossRefGoogle Scholar
  5. 5.
    Wagstaff LR, Mitton MW, Arvik BM, Doraiswamy PM. Statin-associated memory loss: analysis of 60 case reports and review of the literature. Pharmacotherapy. 2003;23:871–80.PubMedCrossRefGoogle Scholar
  6. 6.
    Tierney EF, Thurman DJ, Beckles GL, Cadwell BL. Association of statin use with peripheral neuropathy in the U.S. population 40 years of age or older. J Diabetes. 2013;5:207–15.PubMedCrossRefGoogle Scholar
  7. 7.
    Gaist D, Jeppesen U, Andersen M, Garcia Rodriguez LA, Hallas J, Sindrup SH. Statins and risk of polyneuropathy: a case-control study. Neurology. 2002;58:1333–7.PubMedCrossRefGoogle Scholar
  8. 8.
    Amarenco P, Bogousslavsky J, Callahan III A, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549–59.PubMedCrossRefGoogle Scholar
  9. 9.
    LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425–35.PubMedCrossRefGoogle Scholar
  10. 10.
    Cannon CP, Braunwald E, McCabe CH, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495–504.PubMedCrossRefGoogle Scholar
  11. 11.
    Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143–421.Google Scholar
  12. 12.
    Zaharan NL, Williams D, Bennett K. Statins and risk of treated incident diabetes in a primary care population. Br J Clin Pharmacol. 2013;75:1118–24.PubMedCrossRefGoogle Scholar
  13. 13.
    Sattar N, Preiss D, Murray HM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. Lancet. 2010;375:735–42.PubMedCrossRefGoogle Scholar
  14. 14.
    Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–207.PubMedCrossRefGoogle Scholar
  15. 15.
    Izzo R, de Simone G, Trimarco V, et al. Primary prevention with statins and incident diabetes in hypertensive patients at high cardiovascular risk. Nutr Metab Cardiovasc Dis. 2013. doi: 10.1016/j.numecd.2012.11.002.Google Scholar
  16. 16.
    Ko DT, Wijeysundera HC, Jackevicius CA, Yousef A, Wang J, Tu JV. Diabetes mellitus and cardiovascular events in older patients with myocardial infarction prescribed intensive-dose and moderate-dose statins. Circ Cardiovasc Qual Outcomes. 2013;6:315–22.PubMedCrossRefGoogle Scholar
  17. 17.
    Danaei G, Garcia Rodriguez LA, Fernandez CO, Hernan MA. Statins and risk of diabetes: an analysis of electronic medical records to evaluate possible bias due to differential survival. Diabetes Care. 2013;36:1236–40.PubMedCrossRefGoogle Scholar
  18. 18.
    Waters DD, Ho JE, DeMicco DA, et al. Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials. J Am Coll Cardiol. 2011;57:1535–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Carter AA, Gomes T, Camacho X, Juurlink DN, Shah BR, Mamdani MM. Risk of incident diabetes among patients treated with statins: population based study. BMJ. 2013;346:f2610.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Yamakawa T, Takano T, Tanaka S, Kadonosono K, Terauchi Y. Influence of pitavastatin on glucose tolerance in patients with type 2 diabetes mellitus. J Atheroscler Thromb. 2008 October;15:269–75.Google Scholar
  21. 21.
    Gupta AK, Dahlof B, Dobson J, Sever PS, Wedel H, Poulter NR. Determinants of new-onset diabetes among 19,257 hypertensive patients randomized in the Anglo-Scandinavian Cardiac Outcomes Trial–Blood Pressure Lowering Arm and the relative influence of antihypertensive medication. Diabetes Care. 2008 May;31:982–8.Google Scholar
  22. 22.
    Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007;369:201–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Clore JN, Thurby-Hay L. Glucocorticoid-induced hyperglycemia. Endocr Pract. 2009;15:469–74.PubMedCrossRefGoogle Scholar
  24. 24.
    Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol. 2010;55:1209–16.PubMedCentralPubMedCrossRefGoogle Scholar
  25. 25.
    Baker WL, Talati R, White CM, Coleman CI. Differing effect of statins on insulin sensitivity in non-diabetics: a systematic review and meta-analysis. Diabetes Res Clin Pract. 2010;87:98–107.PubMedCrossRefGoogle Scholar
  26. 26.
    Zhou Y, Yuan Y, Cai RR, et al. Statin therapy on glycaemic control in type 2 diabetes: a meta-analysis. Expert Opin Pharmacother. 2013;14:1575–84.PubMedCrossRefGoogle Scholar
  27. 27.
    Mallinson JE, Constantin-Teodosiu D, Sidaway J, Westwood FR, Greenhaff PL. Blunted Akt/FOXO signalling and activation of genes controlling atrophy and fuel use in statin myopathy. J Physiol. 2009;587:219–30.PubMedCentralPubMedCrossRefGoogle Scholar
  28. 28.
    Bruckert E, Hayem G, Dejager S, Yau C, Begaud B. Mild to moderate muscular symptoms with high-dosage statin therapy in hyperlipidemic patients–the PRIMO study. Cardiovasc Drugs Ther. 2005;19:403–14.PubMedCrossRefGoogle Scholar
  29. 29.
    Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, Yada T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia. 2006;49:1881–92.PubMedCrossRefGoogle Scholar
  30. 30.
    Yada T, Nakata M, Shiraishi T, Kakei M. Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca2+ signalling and insulin secretion due to blockade of L-type Ca2+ channels in rat islet beta-cells. Br J Pharmacol. 1999;126:1205–13.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Kodama Y, Kitta Y, Nakamura T, et al. Atorvastatin increases plasma soluble Fms-like tyrosine kinase-1 and decreases vascular endothelial growth factor and placental growth factor in association with improvement of ventricular function in acute myocardial infarction. J Am Coll Cardiol. 2006;48:43–50.PubMedCrossRefGoogle Scholar
  32. 32.
    Mita T, Watada H, Nakayama S, et al. Preferable effect of pravastatin compared to atorvastatin on beta cell function in Japanese early-state type 2 diabetes with hypercholesterolemia. Endocr J. 2007;54:441–7.PubMedCrossRefGoogle Scholar
  33. 33.
    Costa A, Casamitjana R, Casals E, et al. Effects of atorvastatin on glucose homeostasis, postprandial triglyceride response and C-reactive protein in subjects with impaired fasting glucose. Diabet Med. 2003;20:743–5.PubMedCrossRefGoogle Scholar
  34. 34.
    Huptas S, Geiss HC, Otto C, Parhofer KG. Effect of atorvastatin (10 mg/day) on glucose metabolism in patients with the metabolic syndrome. Am J Cardiol. 2006;98:66–9.PubMedCrossRefGoogle Scholar
  35. 35.
    Wallach-Kildemoes H, Andersen M, Diderichsen F, Lange T. Adherence to preventive statin therapy according to socioeconomic position. Eur J Clin Pharmacol. 2013;69:1553–63.PubMedCrossRefGoogle Scholar
  36. 36.
    Araki M, Maeda M, Motojima K. Hydrophobic statins induce autophagy and cell death in human rhabdomyosarcoma cells by depleting geranylgeranyl diphosphate. Eur J Pharmacol. 2012;674:95–103.PubMedCrossRefGoogle Scholar
  37. 37.
    Calderon RM, Cubeddu LX, Goldberg RB, Schiff ER. Statins in the treatment of dyslipidemia in the presence of elevated liver aminotransferase levels: a therapeutic dilemma. Mayo Clin Proc. 2010;85:349–56.PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Cenedella RJ. Cholesterol and cataracts. Surv Ophthalmol. 1996;40:320–37.PubMedCrossRefGoogle Scholar
  39. 39.
    Machan CM, Hrynchak PK, Irving EL. Age-related cataract is associated with type 2 diabetes and statin use. Optom Vis Sci. 2012;89:1165–71.PubMedCrossRefGoogle Scholar
  40. 40.
    Schmeer C, Gamez A, Tausch S, Witte OW, Isenmann S. Statins modulate heat shock protein expression and enhance retinal ganglion cell survival after transient retinal ischemia/reperfusion in vivo. Invest Ophthalmol Vis Sci. 2008;49:4971–81.PubMedCrossRefGoogle Scholar
  41. 41.
    VanderBeek BL, Zacks DN, Talwar N, Nan B, Stein JD. Role of statins in the development and progression of age-related macular degeneration. Retina. 2013;33:414–22.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Mosiewicz J, Pietrzak A, Chodorowska G, et al. Rational for statin use in psoriatic patients. Arch Dermatol Res. 2013;305:467–72.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of Medicine, Division of CardiologyWeill Cornell Medical CollegeNew YorkUSA

Personalised recommendations