Highlights
- •We assessed the diabetes risk among individuals taking statin ± ezetimibe.
- •No difference was found between the various statins.
- •High-intensity statins were related with a higher diabetes risk in prediabetic individuals.
- •The addition of ezetimibe to statin therapy had a neutral effect on glucose metabolism.
Objective
To assess the risk of progression from normoglycemia or prediabetes to overt diabetes
among individuals treated with statins alone or in combination with ezetimibe.
Methods
This was a retrospective study conducted in Greece including 877 subjects treated
for dyslipidemia. We included individuals without overt diabetes at baseline and divided
them in 2 subgroups according to their baseline fasting glucose: <100 (normal glucose)
and 100 to 125 mg/dL (prediabetes). High and moderate-intensity statin therapy was
defined according to the expected low-density lipoprotein cholesterol reduction (≥50%
and 30 to <50%, respectively). We identified the predictors of incident diabetes and
assessed the risk of new-onset diabetes among subgroups on various intensity statin
or no statin treatment at all. Similar analyses were performed across different potency
of statin monotherapy or combination of statin plus ezetimibe treatment.
Results
A total of 877 subjects were eligible and followed-up for a median of 7 years. There
were no differences between statins regarding diabetes development. However, a higher
risk of incident diabetes was observed in prediabetic individuals receiving high-intensity
statin therapy compared with those on moderate intensity (adjusted odds ratio [OR] =
2.12, 95% confidence interval [CI] = 1.06–4.24, P < .05) and those not taking a statin (adjusted OR = 4.90; 95% CI = 1.16–20.66, P < .05). The addition of ezetimibe to statin treatment did not increase the risk of
incident diabetes in prediabetic individuals (adjusted OR = 0.89; 95% CI = 0.36–2.22,
P > .05). Baseline fasting glucose, presence of metabolic syndrome, family history
of diabetes, and follow-up duration were independent predictors of new-onset diabetes.
Conclusion
High-intensity statin treatment is associated with a higher risk of incident diabetes
in prediabetic individuals, whereas the addition of ezetimibe to statin therapy has
a neutral effect on glucose metabolism.
Keywords
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References
- ESC/EAS Guidelines for the management of dyslipidaemias: the Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).Eur Heart J. 2011; 32: 1769-1818
- The safety of statins in clinical practice.Lancet. 2007; 370: 1781-1790
- Statin therapy and risk of developing type 2 diabetes: a meta-analysis.Diabetes Care. 2009; 32: 1924-1929
- Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.Lancet. 2010; 375: 735-742
- Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.N Engl J Med. 2008; 359: 2195-2207
- 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: 1149-1158
- High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial.JAMA. 2005; 294: 2437-2445
- Differential metabolic effects of distinct statins.Atherosclerosis. 2011; 215: 1-8
- Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases.BMJ. 2014; 348: g3244
- Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.Jama. 2011; 305: 2556-2564
- Lipid-lowering therapies, glucose control and incident diabetes: evidence, mechanisms and clinical implications.Cardiovasc Drugs Ther. 2014; 28: 361-377
- How effective are the ESC/EAS and 2013 ACC/AHA guidelines in treating dyslipidemia? Lessons from a lipid clinic.Curr Med Res Opin. 2015; 31: 221-228
- ESC guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD - summary.Diab Vasc Dis Res. 2014; 11: 133-173
- Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity.Circulation. 2009; 120: 1640-1645
- 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
- Risk of incident diabetes among patients treated with statins: population based study.BMJ. 2013; 346: f2610
- Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials.J Am Coll Cardiol. 2011; 57: 1535-1545
- Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort.Diabetologia. 2015; 58: 1109-1117
- Statins and diabetes.Cardiol Clin. 2015; 33: 233-243
- An assessment by the Statin Diabetes Safety Task Force: 2014 update.J Clin Lipidol. 2014; 8: S17-S29
- Statin-associated incident diabetes: a literature review.Consult Pharm. 2014; 29: 317-334
- The use of statins in people at risk of developing diabetes mellitus: evidence and guidance for clinical practice.Atheroscler Suppl. 2014; 15: 1-15
- Ezetimibe added to statin therapy after acute coronary syndromes.N Engl J Med. 2015; 372: 2387-2397
- Cardiometabolic impact of non-statin lipid lowering therapies.Curr Atheroscler Rep. 2014; 16: 390
- Ezetimibe does not increase fasting glucose levels more than statins alone in non-diabetic hypercholesterolemic patients.JACC. 2015; 65
- Lipid-altering efficacy and safety profile of combination therapy with ezetimibe/statin vs. statin monotherapy in patients with and without diabetes: an analysis of pooled data from 27 clinical trials.Diabetes Obes Metab. 2011; 13: 615-628
- A randomized, double-blind, placebo-controlled study of the effect of ezetimibe on glucose metabolism in subjects with type 2 diabetes mellitus and hypercholesterolemia.Lipids Health Dis. 2015; 14: 40
- New-onset Diabetes Mellitus in the IMPROVE-IT Trial (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial).ESC congress, London2015: 2015
- Prediabetes: a high-risk state for diabetes development.Lancet. 2012; 379: 2279-2290
- The prevalence of the metabolic syndrome in Greece: the MetS-Greece Multicentre Study.Diabetes Obes Metab. 2005; 7: 397-405
Article info
Publication history
Published online: December 07, 2015
Accepted:
November 26,
2015
Received:
May 26,
2015
Identification
Copyright
© 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.
