Skip to main content
SpringerLink
Log in

Statins and Incident Diabetes: Can Risk Outweigh Benefit?

  • Diabetes + Insulin Resistance (M Rutter, Section Editor)
  • Published:
Current Cardiovascular Risk Reports Aims and scope Submit manuscript

Abstract

We review the most recent data regarding the association of incident diabetes and statin use, examine potential mechanisms to explain this association, and compare the potential risk of diabetes with the known cardiovascular benefits derived from statin use. We discuss new and interesting findings, as well as significant trends and developments. The risk of statin-induced dysglycemia and diabetes appears to be dose-dependent, but generally small in magnitude and confined to an unmasking of a strong predisposition to diabetes or accelerated diagnosis in individuals with diabetes risk factors. We focus on the concept of net benefit and find that although risk of diabetes could outweigh cardiovascular benefits in select individuals at low cardiovascular risk, the vast majority of people being managed for cardiovascular risk are most likely to derive net benefit. The need to weigh risks and benefits highlights the importance of shared decision-making in clinician-patient risk discussions.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

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

  1. Blaha MJ, Martin SS. How do statins work? Changing paradigms with implications for statin allocation. J Am Coll Cardiol. 2013;62:2392–4.

    Article  PubMed  Google Scholar 

  2. 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.

    Article  CAS  PubMed  Google Scholar 

  3. Cholesterol Treatment Trialists Collaboration, Baigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376:1670–81.

    Article  Google Scholar 

  4. Stone NJ, Robinson JG, 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. Circulation. 2014;129:S1–45. These contemporary US guidelines provide a summary of randomized controlled evidence for statin-related diabetes risk. They advise on the implications for clinical practice, emphasizing the concept of net benefit, and importance of clinician-patient discusssions.

    Article  PubMed  Google Scholar 

  5. Ioannidis JP. More than a billion people taking statins? Potential implications of the new cardiovascular guidelines. JAMA. 2014;311:463–4.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  7. Ridker PM, Cook NR. Statins: new American guidelines for prevention of cardiovascular disease. Lancet. 2013;382:1762–5.

    Article  PubMed  Google Scholar 

  8. Martin SS, Abd TT, Jones SR, et al. 2013 ACC/AHA cholesterol treatment guideline: what was done well and what could be done better. J Am Coll Cardiol. 2014;63:2674–8.

    Article  PubMed  Google Scholar 

  9. Martin SS, Blumenthal RS. Concepts and controversies: the 2013 American College of Cardiology/American Heart Association risk assessment and cholesterol treatment guidelines. Ann Intern Med. 2014;160:356–8.

    Article  PubMed  Google Scholar 

  10. Desai CS, Martin SS, Blumenthal RS. Non-cardiovascular effects associated with statins. BMJ. 2014;349:g3743.

    Article  PubMed  Google Scholar 

  11. 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.

    Article  CAS  PubMed  Google Scholar 

  12. 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.

    Article  CAS  PubMed  Google Scholar 

  13. Sever PS, Dahlof B, Poulter NR, et al. 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;361:1149–58.

    Article  CAS  PubMed  Google Scholar 

  14. Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005–16.

    Article  PubMed  Google Scholar 

  15. Keech A, Colquhoun D, Best J, et al. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Diabetes Care. 2003;26:2713–21.

    Article  CAS  PubMed  Google Scholar 

  16. Coleman CI, Reinhart K, Kluger J, White CM. The effect of statins on the development of new-onset type 2 diabetes: a meta-analysis of randomized controlled trials. Curr Med Res Opin. 2008;24:1359–62.

    Article  PubMed  Google Scholar 

  17. 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 of 5 statin trials provided novel information on the dose-dependent nature of statin-related diabetes.

    Article  CAS  PubMed  Google Scholar 

  18. Rajpathak SN, Kumbhani DJ, Crandall J, et al. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32:1924–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. 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. Performed in the setting of conflicting prior evidence, this meta-analysis established a relationship between statin use and incident diabetes. The analysis showed that the risk was small both in absolute terms and in comparison to cardiovascular benefits.

    Article  CAS  PubMed  Google Scholar 

  20. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Danaei G, Garcia Rodriguez LA, Fernandez Cantero O, 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  22. Barzilay JI, Davis BR, Pressel SL, et al. Long-term effects of incident diabetes mellitus on cardiovascular outcomes in people treated for hypertension: the ALLHAT Diabetes Extension Study. Circ Cardiovasc Qual Outcomes. 2012;5:153–62.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Nielsen SF, Nordestgaard BG. Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study. Lancet Diab Endocrinol. 2014;2:894–900.

    Article  CAS  Google Scholar 

  24. Culver AL, Ockene IS, Balasubramanian R, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Women’s Health Initiative. Arch Intern Med. 2012;172:144–52.

    Article  PubMed  Google Scholar 

  25. Carter AA, Gomes T, Camacho X, et al. Risk of incident diabetes among patients treated with statins: population based study. BMJ. 2013;346:f2610.

    Article  PubMed Central  PubMed  Google Scholar 

  26. Navarese EP, Buffon A, Andreotti F, 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.

    Article  CAS  PubMed  Google Scholar 

  27. 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.

    Article  CAS  PubMed  Google Scholar 

  28. Bangalore S, Parkar S, Grossman E, Messerli FH. A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus. Am J Cardiol. 2007;100:1254–62.

    Article  CAS  PubMed  Google Scholar 

  29. Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007;369:201–7.

    Article  CAS  PubMed  Google Scholar 

  30. Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380:565–71. As the largest primary prevention trial to date, JUPITER provided especially important information on diabetes risk. JUPITER showed that statin-related diabetes risk was present in those with one of four major risk factors for diabetes.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. 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.

    Article  CAS  PubMed  Google Scholar 

  32. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  34. 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.

    Article  CAS  PubMed  Google Scholar 

  35. Takaguri A, Satoh K, Itagaki M, et al. Effects of atorvastatin and pravastatin on signal transduction related to glucose uptake in 3T3L1 adipocytes. J Pharmacol Sci. 2008;107:80–9.

    Article  CAS  PubMed  Google Scholar 

  36. Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002;8:731–7.

    Article  CAS  PubMed  Google Scholar 

  37. Chetboun M, Abitbol G, Rozenberg K, et al. Maintenance of redox state and pancreatic beta-cell function: role of leptin and adiponectin. J Cell Biochem. 2012;113:1966–76.

    Article  CAS  PubMed  Google Scholar 

  38. Maeda T, Horiuchi N. Simvastatin suppresses leptin expression in 3T3-L1 adipocytes via activation of the cyclic AMP-PKA pathway induced by inhibition of protein prenylation. J Biochem. 2009;145:771–81.

    Article  CAS  PubMed  Google Scholar 

  39. Martin SS, Qasim A, Reilly MP. Leptin resistance: a possible interface of inflammation and metabolism in obesity-related cardiovascular disease. J Am Coll Cardiol. 2008;52:1201–10.

    Article  CAS  PubMed  Google Scholar 

  40. 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.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  41. Xia F, Xie L, Mihic A, et al. Inhibition of cholesterol biosynthesis impairs insulin secretion and voltage-gated calcium channel function in pancreatic beta-cells. Endocrinology. 2008;149:5136–45.

    Article  CAS  PubMed  Google Scholar 

  42. 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. 2014. doi:10.1016/S0140-6736(14)61183-1.

    PubMed  Google Scholar 

  43. Cholesterol Treatment Trialists Collaboration, Kearney PM, Blackwell L, et al. Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet. 2008;371:117–25.

    Article  Google Scholar 

  44. United States Food and Drug Administration Consumer Health Information. FDA expands advice on statin risks. Available at: http://www.fda.gov/downloads/ForConsumers/ConsumerUpdates/UCM293705.pdf. Accessed December 4th, 2014.

Download references

Acknowledgments

SSM is supported by the Pollin Cardiovascular Prevention Fellowship, Marie-Josée and Henry R. Kravis endowed fellowship, and a National Institutes of Health training grant (T32HL07024). RSB is supported by the Kenneth Jay Pollin Professorship in Cardiology. The authors did not receive any dedicated funding to write this article.

Compliance with Ethics Guidelines

ᅟ

Conflict of Interest

Roger Blumenthal and Roberta Florido have no disclosures. Seth Martin is listed as a co-inventor on a pending patent filed by Johns Hopkins University for a method of low-density lipoprotein cholesterol estimation.

Human and Animal Rights and Informed Consent

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

Author information

Authors and Affiliations

  1. Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, MD, USA

    Roberta Florido, Annie Elander, Roger S. Blumenthal & Seth S. Martin

  2. The Johns Hopkins Hospital, 1800 Orleans St, Zayed 7125, Baltimore, MD, 21287, USA

    Roberta Florido, Roger S. Blumenthal & Seth S. Martin

Authors
  1. Roberta Florido
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Annie Elander
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Roger S. Blumenthal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seth S. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberta Florido.

Additional information

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Florido, R., Elander, A., Blumenthal, R.S. et al. Statins and Incident Diabetes: Can Risk Outweigh Benefit?. Curr Cardiovasc Risk Rep 9, 14 (2015). https://doi.org/10.1007/s12170-015-0444-7

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s12170-015-0444-7

Keywords

Search

Navigation