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


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

BOTTOM LINE
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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EVIDENCE
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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Author(s):

  • 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.