Tools for Practice

#90 Statin-Induced Diabetes: Too Sweet a Deal?

Do statins increase the risk of diabetes, and does this worsen outcomes?

Statins modestly increase blood glucose, which leads to an extra one in 250 patients crossing the “diabetic threshold” over 4 years. This should not change statin prescribing, as they reduce cardiovascular events and all-cause mortality in appropriate patients.

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Statin versus no statin: 
  • Meta-analysis1 of 13 randomized controlled trials (RCTs) with 91,140 patients with, or at high risk for, cardiovascular disease: 
    • New diabetes over 4 years: Statins 4.9%, control 4.5%, number needed to harm (NNH)=250. 
  • Similar results in meta-analysis of 15 RCTs (91,828 patients):2 odds ratio 1.11 (95% confidence interval 1.03-1.20). 
High versus low/moderate dose statin (e.g. atorvastatin 80 mg versus 10 mg): 
  • Meta-analysis3 of 5 RCTs with 32,752 patients with cardiovascular disease: 
    • New diabetes over 5 years: High-dose 8.8%, low/moderate-dose 8%, NNH=125. 
Observational studies confirm increased diabetes diagnosis with statin versus no statin,4-6 and higher versus lower statin dose or potency7,8 seen in RCTs.  Context:  
  • Diagnosis of type 2 diabetes is largely based on crossing an arbitrary laboratory threshold, like fasting plasma glucose (FPG) >7.0 mmol/L:9 
    • Baseline FPG 6.0-6.9 mmol/L is a risk factor for developing diabetes with statins10 
    • In an observational study, FPG increased by 0.1 mmol/L at 2 years in non-diabetics taking statins11 
    • Thus, the increase in diabetes diagnoses in statin users is mostly from patients with borderline glucose levels crossing the diagnostic cutoff. 
  • Genetic studies showed that having mutations that impair HMG-CoA reductase activity is associated with greater FPG and higher incidence of type 2 diabetes2 
    • Confirms that risk of diabetes with statins tied to their LDL-lowering potency. 
  • Despite the increase in blood glucose, statins reduce important clinical outcomes including mortality in patients with an appropriate indication:5,12 
    • In the Heart Protection Study:12 for every 1 person newly diagnosed with diabetes due to statin use over 5 years, statins prevented 5 deaths, 6 non-fatal myocardial infarctions and 4 strokes. 
  • Thiazides and beta-blockers also increase the risk of diabetes versus placebo or other antihypertensives14 
    • Both classes15,16 provide net benefit in appropriate patients.  
Aug 12 2016 Ricky Turgeon BSc(Pharm) ACPR PharmD

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  • G. Michael Allan MD CCFP
  • Ricky Turgeon BSc(Pharm) ACPR PharmD

1. Sattar N, Preiss D, Murray HM, et al. Lancet 2010;375:735-42.

2. Swedlow DI, Preiss D, Kuchenbaecker KB, et al. Lancet 2015;385:351-61.

3. Preiss D, Seshasai SR, Welsh P, et al. JAMA 2011;305:2556-64.

4. Culver AL, Ockene IS, Balasubramanian R, et al. Arch Intern Med 2012;172:144-52.

5. Wang KL, Liu CJ, Chao TF, et al. J Am Coll Cardiol 2012;60:1231-8.

6. Shen L, Shah BR, Reyes EM, et al. BMJ 2013;347:f6745.

7. Carter AA, Gomes T, Camacho X, et al. BMJ 2013;346:f2610.

8. Dormuth CR, Filion KB, Paterson JM, et al. BMJ 2014;348:g3244.

9. Canadian Diabetes Association Clinical Practice Guidelines Expert Committee. Can J Diabetes 2013;37:S8-S11.

10. Waters DD, Ho JE, DeMicco DA, et al. J Am Coll Cardiol 2011;57:1535-45.

11. Sukhija R, Prayaga S, Marashdeh M, et al. J Investig Med 2009;57:495-9.

12. Wilt TJ, Bloomfield HE, MacDonald R, et al. Arch Intern Med 2004;164:1427-36.

13. Heart Protection Study Collaboration Group. Lancet 2002;360:7-22.

14. Elliott WJ, Meyer PM. Lancet 2007; 369:201-7.

15. ALLHAT Collaborative Research Group. JAMA 2002;288:2981-97.

16. Ko DT, Hebert PR, Coffey CS, et al. Arch Intern Med 2004;164:1389-94.

Authors do not have any conflicts of interest to declare.