Skip to main content

Role of Statins in Glucose Homeostasis and Insulin Resistance


Statins are widely used for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), and, under the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol treatment guidelines, more individuals are eligible for statin therapy. In this review, we summarize evidence for a mild increase in serum glucose and increased incidence of diabetes associated with statins, the hypothesized mechanisms by which statins may impair glucose homeostasis, the risk of diabetes associated with particular statins, and the net effect on ASCVD risk. As emphasized by the ACC/AHA guideline group and other experts, the risk-reducing benefits of statin therapy generally outweigh the mild rise in glucose levels or new diagnoses of diabetes. As such, an appropriate balancing of benefits and risks is critical in clinical practice as clinicians engage patients in shared decision making. Moreover, when discussing statins and risk of diabetes, this is a prime opportunity for clinicians to provide further counseling on the central importance of weight loss and adhering to a healthy lifestyle in glucose homeostasis and diabetes prevention.

This is a preview of subscription content, access via your institution.


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

  1. 1.

    •• Stone NJ, Robinson JG, Lichtenstein AH, et al. 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. Circulation. 2014;129:S1–45. This is an important reference for up-to-date guidelines regarding the treatment of hyperlipidemia for reducing ASCVD.

    Article  PubMed  Google Scholar 

  2. 2.

    • Martin SS, Sperling LS, Blaha MJ, et al. Clinician-patient risk discussion for atherosclerotic cardiovascular disease prevention: importance to implementation of the 2013 ACC/AHA Guidelines. J Am Coll Cardiol. 2015;65(13):1361–8. doi:10.1016/j.jacc.2015.01.043. Discusses the importance of clinician-patient risk discussion in prevention of ASCVD and when initiating statin therapy in conjunction with 2013 ACC/AHA guidelines.

    Article  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Pencina MJ, Navar-Boggan AM, D’Agostino RB, et al. Application of new cholesterol guidelines to a population-based sample. N Engl J Med. 2014;370:1422–31.

    CAS  Article  PubMed  Google Scholar 

  4. 4.

    National Center for Health Statistics. Health, United States 2010: with special feature on death and dying. National Center for Health Statistics, Hyattsville, MD; 2011.

  5. 5.

    FDA-Administration. FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs. Secondary FDA Drug Safety Communication: important safety label changes to cholesterol-lowering statin drugs. 2012.

  6. 6.

    • Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380:565–71. Reviews findings from the JUPITER trial showing that the benefits of statins outweigh the risk of new-onset DM in patients who are at high-risk of developing diabetes.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. 7.

    Waters DD, Ho JE, Boekholdt SM, et al. Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes. J Am Coll Cardiol. 2013;61:148–52.

    CAS  Article  PubMed  Google Scholar 

  8. 8.

    Ridker PM, Danielson E, Fonseca FA, JUPITER Study Group, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207. doi:10.1056/NEJMoa0807646.

    CAS  Article  PubMed  Google Scholar 

  9. 9.

    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. doi:10.1136/bmj.f2610.

    Article  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Erqou S, Lee CC, Adler AI. Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis. Diabetologia. 2014;57:2444–52. doi:10.1007/s00125-014-3374-x.

    CAS  Article  PubMed  Google Scholar 

  11. 11.

    Lin ZF, Wang CY, Shen LJ, Hsiao FY, Lin Wu FL. Statin use and the risk for incident diabetes mellitus in patients with acute coronary syndrome after percutaneous coronary intervention: a population-based retrospective cohort study in Taiwan. Can J Diabetes. 2016;S1499-2671(15):30026–5. doi:10.1016/j.jcjd.2015.12.006.

    Google Scholar 

  12. 12.

    Yusuf S, Bosch J, Dagenais G, et al; HOPE-3 Investigators. Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med. 2016.

  13. 13.

    Freeman DJ, Norrie J, Sattar N, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001;103:357–62.

    CAS  Article  PubMed  Google Scholar 

  14. 14.

    Teramoto T, Shimano H, Yokote K, Urashima M. New evidence on pitavastatin: efficacy and safety in clinical studies. Expert Opin Pharmacother. 2010;11:817–28. doi:10.1517/14656561003641990.

    CAS  Article  PubMed  Google Scholar 

  15. 15.

    Goldfine AB. Statins: is it really time to reassess benefits and risks? N Engl J Med. 2012;366:1752–5.

    CAS  Article  PubMed  Google Scholar 

  16. 16.

    Nakata M, Nagasaka S, Kusaka I, et al. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycaemic control. Diabetologia. 2006;49:1881–92.

    CAS  Article  PubMed  Google Scholar 

  17. 17.

    Nowis D, Malenda A, Furs K, et al. Statins impair glucose uptake in human cells. BMJ Open Diabetes Res Care. 2014;2(1):e000017. doi:10.1136/bmjdrc-2014-000017.

    Article  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Brault M, Ray J, Gomez YH, Mantzoros CS, Daskalopoulou SS. Statin treatment and new-onset diabetes: a review of proposed mechanisms. Metabolism. 2014;63:735–45.

    CAS  Article  PubMed  Google Scholar 

  19. 19.

    Aiman U, Najmi A, Khan RA. Statin induced diabetes and its clinical implications. J Pharmacol Pharmacother. 2014;5(3):181–5. doi:10.4103/0976-500X.136097.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. 20.

    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.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  21. 21.

    Ricci R, Bevilacqua F. The potential role of leptin and adiponectin in obesity: a comparative review. Vet J. 2012;191:292–8.

    CAS  Article  PubMed  Google Scholar 

  22. 22.

    Reddy KJ, Singh M, Bangit JR, Batsell RR. The role of insulin resistance in the pathogenesis of atherosclerotic cardiovascular disease: an updated review. J Cardiovasc Med. 2010;11:633–47.

    Article  Google Scholar 

  23. 23.

    Jung CH, Rhee EJ, Choi JH, et al. The relationship of adiponectin/leptin ratio with homeostasis model assessment insulin resistance index and metabolic syndrome in apparently healthy Korean male adults. Korean Diabetes J. 2010;34:237–43.

    Article  PubMed  PubMed Central  Google Scholar 

  24. 24.

    Kajikawa Y, Ikeda M, Takemoto S, Tomoda J, Ohmaru N, Kusachi S. Association of circulating levels of leptin and adiponectin with metabolic syndrome and coronary heart disease in patients with various coronary risk factors. Int Heart J. 2011;52:17–22.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Chrusciel P, Sahebkar A, Rembek-Wieliczko M, et al. Lipid and blood pressure meta-analysis collaboration (LBPMC) group. Impact of statin therapy on plasma adiponectin concentrations: a systematic review and meta-analysis of 43 randomized controlled trial arms. Atherosclerosis. 2016. doi:10.1016/j.atherosclerosis.2016.07.897.

    PubMed  Google Scholar 

  26. 26.

    Dubey L, Hesong Z. Role of leptin in atherogenesis. Exp Clin Cardiol. 2006;11:269–75.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Seufert J. Leptin effects on pancreatic beta-cell gene expression and function. Diabetes. 2004;53:S152–8. doi:10.2337/diabetes.53.2007.S152.

    CAS  Article  PubMed  Google Scholar 

  28. 28.

    Marroquí L, Gonzalez A, Ñeco P, et al. Role of leptin in the pancreatic β-cell: effects and signaling pathways. J Mol Endocrinol. 2012;49:R9–R17.

    Article  PubMed  Google Scholar 

  29. 29.

    Amitani M, Asakawa A, Amitani H, Inui A. The role of leptin in the control of insulin-glucose axis. Front Neurosci. 2013;7:51.

    Article  PubMed  PubMed Central  Google Scholar 

  30. 30.

    Thorp AA, Schlaich MP. Relevance of sympathetic nervous system activation in obesity and metabolic syndrome. J Diabetes Res. 2015;2015:341583.

    Article  PubMed  PubMed Central  Google Scholar 

  31. 31.

    Kain V, Kapadia B, Misra P, Saxena U. Simvastatin may induce insulin resistance through a novel fatty acid mediated cholesterol independent mechanism. Sci Rep. 2015;5:13823. doi:10.1038/srep13823.

    Article  PubMed  PubMed Central  Google Scholar 

  32. 32.

    Swerdlow DI, Preiss D, Kuchenbaecker KB, et al. HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials. Lancet. 2015;385:351–61.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  33. 33.

    Besseling J, Kastelein JJ, Defesche JC, Hutten BA, Hovingh GK. Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus. JAMA. 2015;313(10):1029–36. doi:10.1001/jama.2015.1206.

    CAS  Article  PubMed  Google Scholar 

  34. 34.

    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(24):2556–64. doi:10.1001/jama.2011.860.

    CAS  Article  PubMed  Google Scholar 

  35. 35.

    Navarese EP, Buffon A, Andreotti F, Kozinski M, Welton N, Fabiszak T, et al. Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am J Cardiol. 2013;111:1123–30.

    CAS  Article  PubMed  Google Scholar 

  36. 36.

    Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016. doi:10.1016/S0140-6736(16)31357-5.

    PubMed Central  Google Scholar 

  37. 37.

    Florido R, Elander A, Blumenthal RS, Martin SS. Statins and incident diabetes: can risk outweigh benefit? Curr Cardiovasc Risk Rep. 2015;9:14. doi:10.1007/s12170-015-0444-7.

    Article  Google Scholar 

  38. 38.

    Su X, Zhang L, Lv J, et al. Effect of statins on kidney disease outcomes: a systematic review and meta-analysis. Am J Kidney Dis. 2016;67:881–92.

    CAS  Article  PubMed  Google Scholar 

  39. 39.

    The SHARP Collaborative Group. Effects of lowering LDL cholesterol on progression of kidney disease. J Am Soc Nephrol. 2014;25:1825–33.

    Article  Google Scholar 

  40. 40.

    Ueshima K, Itoh H, Kanazawa N, et al. Rationale and design of the standard versus intensive statin therapy for hypercholesterolemic patients with diabetic retinopathy (EMPATHY) study: a randomized controlled trial. J Atheroscler Thromb. 2016;23:976–90.

    Article  PubMed  Google Scholar 

  41. 41.

    Laties AM, Shear CL, Lippa EA, et al. Expanded clinical evaluation of lovastatin (EXCEL) study results. II. Assessment of the human lens after 48 weeks of treatment with lovastatin. Am J Cardiol. 1991;67:447–53.

    CAS  Article  PubMed  Google Scholar 

  42. 42.

    Pedersen TR, Berg K, Cook TJ, et al. Safety and tolerability of cholesterol lowering with simvastatin during 5 years in the Scandinavian Simvastatin Survival Study. Arch Intern Med. 1996;156:2085–92.

    CAS  Article  PubMed  Google Scholar 

  43. 43.

    Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–9. doi:10.1016/S0140-6736(94)90566-5.

    Google Scholar 

  44. 44.

    Shepherd J, Cobbe S, Ford I. West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. N Engl J Med. 1995;333:1301–8. doi:10.1056/NEJM199511163332001.

    CAS  Article  PubMed  Google Scholar 

  45. 45.

    Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279(20):1615–22. doi:10.1001/jama.279.20.1615.

    CAS  Article  PubMed  Google Scholar 

  46. 46.

    The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349–57. doi:10.1056/NEJM199811053391902.

    Article  Google Scholar 

  47. 47.

    GISSI Prevenzione Investigators (Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico). Results of the low-dose (20 mg) pravastatin GISSI Prevenzione trial in 4271 patients with recent myocardial infarction: do stopped trials contribute to overall knowledge? Ital Heart J. 2000;1(12):810–20.

    Google Scholar 

  48. 48.

    Collins R, Armitage J, Parish S, Sleigh P, Peto R. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361(9374):2005–16. doi:10.1016/S0140-6736(03)13636-7.

    Article  PubMed  Google Scholar 

  49. 49.

    Shepherd J, Blauw GJ, Murphy MB, PROSPER Study Group, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623–30. doi:10.1016/S0140-6736(02)11600-X.

    CAS  Article  PubMed  Google Scholar 

  50. 50.

    ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major outcomes in moderately hypercholesterolemic, hypertensive patients randomized to pravastatin vs usual care: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT-LLT). JAMA. 2002;288(23):2998–3007. doi:10.1001/jama.288.23.2998.

    Article  Google Scholar 

  51. 51.

    Sever PS, Dahlöf B, Poulter NR. et al; ASCOT investigators. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial–Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. 2003;361(9364):1149–58. doi:10.1016/S0140-6736(03)12948-0.

    CAS  Article  PubMed  Google Scholar 

  52. 52.

    Nakamura H, Arakawa K, Itakura H, MEGA Study Group, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006;368(9542):1155–63. doi:10.1016/S0140-6736(06)69472-5.

    CAS  Article  PubMed  Google Scholar 

Download references

Author information



Corresponding author

Correspondence to Seth S. Martin.

Ethics declarations

Conflict of Interest

Drs Dahagam, Hahn, Goud, D’Souza, Abdelqader, and Blumenthal have no conflicts of interest.

Dr. Martin has research support from the David and June Trone Family Foundation, PJ Schafer Cardiovascular Research Fund, American Heart Association, Aetna Foundation, CASCADE FH, Google, and Apple. Dr. Martin is listed as a co-inventor on a pending patent filed by Johns Hopkins University for the novel method of low-density lipoprotein cholesterol estimation. Dr. Martin has served as a consultant to Abbott Nutrition, Pressed Juicery, Quest Diagnostics, Sanofi/Regeneron, Amgen, and the Pew Research Center.

Human and Animal Rights and Informed Consent

This article does not contain studies with human or animal subjects performed by the author.

Additional information

This article is part of the Topical Collection on Diabetes and Insulin Resistance

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Dahagam, C., Hahn, V.S., Goud, A. et al. Role of Statins in Glucose Homeostasis and Insulin Resistance. Curr Cardiovasc Risk Rep 10, 40 (2016).

Download citation


  • Statins
  • Cholesterol
  • Diabetes
  • Hyperglycemia
  • Insulin resistance
  • Cardiovascular disease