Statins and diabetes risk
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  • 1. Statin s and Diabet es between risks and benefits Alexandru Andritoiu Military Hospital Craiova, MD, MPh
  • 2. Drugs that induce diabetes Drugs that cause diabetes by interfering with insulin production and secretion Vacor Tacrolimus Didansoine β-receptor antagonists L-asparaginase Diphenylhydantoin Diazoxide Drugs that cause diabetes by reducing the effectiveness of insulin to regulate metabolism Steroids Glucocorticoids Megasterol acetate β-receptor agonists Growth hormone Protease inhibitors Drugs that act on both insulin secretion and insulin sensitivity Thiazide diuretics Cyclosporine Atypical antipsychotic medications Treatments that induce diabetes by increasing nutrient flux Nicotinic acid Total parenteral nutrition Richard J Coli D. Diabetes Melitus: A Fundamental and Clinical Text. 3rd Edition 2004
  • 3. FDA Expands Advice on Statin Risks (2012)     Routine monitoring of liver enzymes in the blood, once considered standard procedure for statin users, is no longer needed. Such monitoring has not been found to be effective in predicting or preventing the rare occurrences of serious liver injury associated with statin use. Cognitive (brain-related) impairment, such as memory loss, forgetfulness and confusion, has been reported by some statin users. People being treated with statins may have an increased risk of raised blood sugar levels and the development of Type 2 diabetes. Some medications interact with lovastatin (brand names include Mevacor) and can increase the risk of muscle damage.
  • 4.  FDA Adds Diabetes, Memory Loss Warnings to Statins  Reuters  Safety Alerts Cite Cholesterol Drugs’ Side Effects The New York Times  Statin Labels will Come with New Safety Warnings CNN  FDA Adds Safety Warnings to Statins HealthDay  FDA Adds Diabetes Warning to Statin Label MedPage Today
  • 5. To prescribe or not to prescribe: That is the statin question Blumenthal RS. Redberg R. Should healthy people take cholesterol drugs to prevent heart disease? Wall Street Journal, January 23, 2012.
  • 6. The Diabetes Dilemma for Statin Users ERIC J. TOPOL Published: March 4, 2012 ,,We need to find out why statins cause diabetes and, ideally, through genomics we could determine who is at risk for this important side effect. But to date nothing has been done to sort this out — despite the fact that the market for statins is well over $20 billion per year. There are thousands of blood samples sitting in company freezers around the world that could potentially provide the answers”
  • 7. The Lancet, Volume 380, Issue 9841, Pages 565 - 571, 11 August 2012 Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial Paul M Ridker, et al
  • 8. In the JUPITER primary prevention trial, the cardiovascular and mortality benefits of statin therapy exceed the diabetes hazard, including in participants at high risk of developing diabetes.
  • 9. Diabetes Care October 2009; vol. 32: no.10: 1924-1929 Statin Therapy and Risk of Developing Type 2 Diabetes: A Meta-Analysis Swapnil N. Rajpathak, Dharam J. Kumbhani, Jill Crandall, Nir Barzilai, Michael Alderman, Paul M. Ridker. RESULTS In the meta-analysis of the hypothesis-testing trials, we observed a small increase in diabetes risk (RR 1.13 [95% CI 1.03–1.23])
  • 10. Meta-analysis of clinical trials evaluating the effects of statins on diabetes risk
  • 11. June 22; 2011, Vol 305, No. 2 Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy A Meta-analysis David Preiss, Sreenivasa Rao Kondapally Seshasai, Paul Welsh, Sabina A. Murphy, Jennifer E. David D. Waters, David A. DeMicco, Philip Barter, Christopher P. Cannon, Marc S. Sabatine, Eugene Braunwald, John J. P. Kastelein, James A. de Lemos, Michael A. Blazing, Terje R. Pedersen,Matti J. Tikkanen, Naveed Sattar, Kausik K. Ray.
  • 12. INTERPRETATION:  Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events.  Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change.
  • 13. Results    In 5 statin trials with 32.752 participants without diabetes at baseline, 2749 developed diabetes (1449 assigned intensive-dose therapy, 1300 assigned moderate-dose therapy, representing 2.0 additional cases in the intensive-dose group per 1000 patientyears) and 6684 experienced cardiovascular events (3134 and 3550, respectively, representing 6.5 fewer cases in the intensivedose group per 1000 patient-years) over a weighted mean (SD) follow-up of 4.9 (1.9) years. Odds ratios were 1.12 (95% confidence interval [CI], 1.041.22; I2 = 0%) for new-onset diabetes and 0.84 (95% CI, 0.750.94; I2 = 74%) for cardiovascular events for participants receiving intensive therapy compared with moderate-dose therapy. As compared with moderate-dose statin therapy, the number needed to harm per year for intensive-dose statin therapy was 498 for new-onset diabetes while the number needed to treat per year for intensive-dose statin therapy was 155 for cardiovascular events. Conclusion: In a pooled analysis of data from 5 statin trials, intensivedose statin therapy was associated with an increased risk of new-onset diabetes compared with moderate-dose statin therapy.
  • 14. From: Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy: A Metaanalysis JAMA. 2011;305(24):2556-2564. doi:10.1001/jama.2011.860 Figure Legend: Data marker size indicates relative weight of the studies; OR, odds ratio; and CI, confidence interval. Date of download: 9/23/2012 Copyright © 2012 American Medical Association. All rights reserved.
  • 15. From: Risk of Incident Diabetes With Intensive-Dose Compared With Moderate-Dose Statin Therapy: A Metaanalysis JAMA. 2011;305(24):2556-2564. doi:10.1001/jama.2011.860 Figure Legend: Data were available for age, high-density lipoprotein (HDL) cholesterol levels, and triglyceride concentrations in all trials; for body mass index (BMI) in 4 trials; and for fasting plasma glucose levels in 3 trials. The medians of the variables are per-trial medians, which are provided in the eTable. P values apply to heterogeneity between groups. Data marker si ze indicates relative weight of the studies; OR, odds ratio; and CI, confidence interval. Date of download: 9/23/2012 Copyright © 2012 American Medical Association. All rights reserved.
  • 16. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials Sattar N et al.- Lancet 2010;27;375:735-742
  • 17. 13 statin trials 91.140 participants, of whom 4278 (2226 assigned statins and 2052 assigned control treatment) developed diabetes during a mean of 4 years. Statin therapy was associated with a 9% increased risk for incident diabetes (odds ratio [OR] 1·09; 95% CI 1·02—1·17), with little heterogeneity (I2=11%) between trials. Meta-regression showed that risk of development of diabetes with statins was highest in trials with older participants, but neither baseline body-mass index nor change in LDL-cholesterol concentrations accounted for residual variation in risk. Treatment of 255 (95% CI 150—852) patients with statins for 4 years resulted in one extra case of diabetes. Interpretation Statin therapy is associated with a slightly increased risk of development of diabetes, but the risk is low both in absolute terms and when compared with the reduction in coronary events. Clinical practice in patients with moderate or high cardiovascular risk or existing cardiovascular disease should not change. Sattar N et al. Lancet 2010
  • 18. Statin Use and Risk of Diabetes Mellitus in Postmenopausal Women Annie L. Culver, et al. - Arch Intern Med. Published online January 9, 2012
  • 19. Study links statins to higher diabetes in older women Culver AL, Ockene IS, Balasubramanian R Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative. Arch Intern Med 2012;
  • 20.  Results  This investigation included 153 840 women without DM and no missing data at baseline. At baseline, 7.04% reported taking statin medication. There were 10 242 incident cases of self-reported DM over 1 004 466 person-years of follow-up.   Statin use at baseline was associated with an increased risk of DM (hazard ratio [HR], 1.71; 95% CI, 1.61-1.83).  This association remained after adjusting for other potential confounders (multivariate-adjusted HR, 1.48; 95% CI, 1.38-1.59) and was observed for all types of statin medications.  Conclusions  Statin medication use in postmenopausal women is associated with an increased risk for DM.  This may be a medication class effect.  Further study by statin type and dose may reveal varying risk levels for new-onset DM in this population. Subset analyses evaluating the association of self-reported DM with longitudinal measures of statin use in 125 575 women confirmed these findings. Arch Intern Med. Published online January 9, 2012
  • 21. Statins raise risk of Type 2 diabetes in older women Post-menopausal women who take statins to ward off heart attacks are more likely to develop Type 2 diabetes than those who do not, research indicates. January 10, 2012 By Melissa Healy, Los Angeles Times
  • 22. Diabetes/statin link probed in EFFECT cohort World Congress of Cardiology 2012 ,,The message for the public is that statins have documented benefits over many years. The risk of developing diabetes with a statin vs placebo is probably there, but when we talk about dose relationships, we can't find any evidence of a difference between doses," Dr Altayyeb Yousef (Institute for Clinical Evaluative Sciences, Toronto)
  • 23. END POINTS  deaths, deaths or ACS, or new-onset diabetes in the EFFECT study cohort—all patients who had been hospitalized for acute MI. CONCLUSIONS  Comparing results among 2870 matched patients, they found no significant differences in any of those three end points out to five years.  At each year out to five years, the risk of diabetes was actually lower, numerically, among the intensive-statin group as compared with the moderate-dose group, although differences were not statistically significant.
  • 24. Rautio N, Jokelainen J, Oksa H, et al. BMJ 2012 Do statins interfere with lifestyle intervention in the prevention of diabetes in primary healthcare? One-year follow-up of the FIN-D2D project
  • 25.  This is the first study examining the association of lifestyle intervention on the risk of type 2 diabetes according to the use of statins. This question is of utmost clinical importance, since we now know that type 2 diabetes is preventable by lifestyle changes.  Fasting glucose increased by 0.08 mmol/L in statin users but remained unchanged in nonusers. This was a significant difference and remained so after adjustment for age, sex, baseline fasting glucose, presence of CVD, use of antihypertensive and/or CAD medication, weight, and one-year weight change.  An increase in fasting glucose in statin users suggests deterioration in insulin secretion capacity, but added that two-hour glucose values, which reflect insulin sensitivity, were similarly decreased in statin users and nonusers.
  • 26.  "The message for clinicians is that patients who have multiple components of the metabolic syndrome need to try to further improve their lifestyle habits to combat the possible rise in glucose when a statin is begun. This paper suggests that statins may have unfavorable effects on glucose metabolism in certain people, so compliance with lifestyle improvements will be very important. We look forward to more prospective studies on this topic." Dr Nina Rautio -BMJ ; September 13, 2012
  • 27. Statins, Risk of Diabetes, and Implications on Outcomes in the General Population Kang-Ling Wang, et al. J Am Coll Cardiol. 2012;60(14):1231-1238
  • 28. Objectives This study aimed to evaluate the association of statin exposure and incident diabetes, and subsequent outcomes in the general population. Kang-Ling Wang, et al. - J Am Coll Cardiol. 2012;60(14):1231-1238.
  • 29. Results Over a median of 7.2 years, annual rates of diabetes were significantly higher in statin users (2.4% vs. 2.1%; p < 0.001) MACE HR: 0.82; CI 0.68-0.98 for myocardial infarction HR: 0.94; CI 0.86-1.03 for ischemic stroke HR: 0.91; CI:0.84-0.99 for MACE In-hospital mortality HR: 0.61; CI:0.55-0.67 Kang-Ling Wang, et al. - J Am Coll Cardiol. 2012;60(14):1231-1238.
  • 30. The risk–benefit analyses    Statin treatment was favorable in high-risk and secondary prevention populations. Among diabetic patients, prior statin use was associated with fewer MACE In-hospital deaths were similar in statin-related diabetes among high-risk and secondary prevention subjects compared with nondiabetic controls. Conclusions Risk of diabetes was increased after statins, but outcomes were favorable. Kang-Ling Wang, et al. - J Am Coll Cardiol. 2012;60(14):1231-1238
  • 31. Kaplan-Meier Curves for Outcomes Among Statin and Control Groups (A) Cumulative incidences for newly developed diabetes in the statin and control groups were 22.7% and 20.8%, respectively. (B) Cumulative incidences for major adverse cardiovascular (CV) events (the composite of myocardial infarction [MI] and ischemic stroke) in the statin and control groups were 11.6% and 12.6%, (C) Cumulative incidences for in-hospital death from all causes in the statin and control groups were 8.8% and 13.8%. Kang-Ling Wang, et al. - J Am Coll Cardiol. 2012;60(14):1231-1238.
  • 32. J Am Coll Cardiol. 2011;57(14):1535-1545 Predictors of New-Onset Diabetes in Patients Treated with Atorvastatin Results From 3 Large Randomized Clinical Trials David D. Waters, Jennifer E. Ho, David A. DeMicco, Andrei Breazna,Benoit J. Arsenault, Chuan-Chuan Wun, John J. Kastelein, Helen Colhoun, Philip Barter
  • 33. Predictors of New-Onset Diabetes in Patients Treated With Atorvastatin: Results From 3 Large Randomized Clinical Trials J Am Coll Cardiol. 2011;57(14):1535-1545
  • 34. Incident Diabetes According to Number of Risk Factors Incident diabetes in (A) the TNT trial, (B) the IDEAL trial, and (C) the SPARCL trial according to number of risk factors and treatment group. Atorva. = atorvastatin; ATV10 = atorvastatin 10 mg; ATV80 = atorvastatin 80 mg; Simva = simvastatin; J Am Coll Cardiol 2011;57(14):1535-1545
  • 35. Conclusions High-dose atorvastatin treatment (80mg/day) compared with placebo in the SPARCL trial is associated with a slightly increased risk of new-onset T2DM. Baseline fasting glucose level and features of the metabolic syndrome are predictive of new-onset T2DM across the 3 trials. Waters DD et al. J Am Coll Cardiol. 2011;57(14):1535-1545
  • 36. How effective are statins for people with diabetes?
  • 37. Most people with diabetes 'have poor cholesterol control'  Almost three-fifths of people with diabetes do not meet their cholesterol targets  An analysis by Diabetes UK found that more than nine out of ten (91.6 per cent) people with diabetes in England now receive an annual check.  Yet almost 60 per cent of patients are still not meeting their targets, the research revealed.
  • 38. How effective are statins for people with diabetes? Collaborative Atorvastatin Diabetes Study (CARDS) This study involved nearly 3000 people with Type 2 diabetes aged 40-75. It looked at the benefits of taking a 10mg dose of atorvastatin daily. None of the participants had heart disease at the start of the trial, but they did have an extra risk factor for developing it, such as smoking, high blood pressure, diabetic retinopathy or protein in the urine indicating diabetic kidney disease. For those taking the statin, the risk of heart attack reduced by 37 per cent and stroke by 48 per cent. These benefits were seen regardless of age, sex or whether the cholesterol level was high or low. The trial's success meant it was halted two years early.  The Heart Protection Study (HPS) The HPS study involved nearly 6000 people with diabetes aged 40-80. It looked at the benefits of taking a 40mg dose of simvastatin each day. Just under half of the participants showed signs of cardiovascular disease, while half did not. It found this routine use of statins cut the number of heart attacks and strokes in both groups by a third. 
  • 39. CONCLUSI ONS
  • 40. High-Dose Statins May Increase Diabetes Risk but, Experts Say Most Heart Disease Patients Are Better Off Taking a Statin, Despite Increased Diabetes Risk