Differential metabolic effects of distinct statins

Koh, Kwang Kon; Sakuma, Ichiro; Quon, Michael J.

doi:10.1016/j.atherosclerosis.2010.10.036

Cited by 130Lipoproteins and Cardiovascular HealthDiabetes, Cardiovascular Risks, and LipoproteinsCancer, Lipids, and Metabolism

Differential metabolic effects of distinct statins

Koh, Kwang Kon, Sakuma, Ichiro, Quon, Michael J.·2011·Atherosclerosis

DOI 10.1016/j.atherosclerosis.2010.10.036

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Abstract

Reciprocal relationships between endothelial dysfunction and insulin resistance suggest that therapies improving endothelial dysfunction will simultaneously improve insulin sensitivity and other metabolic parameters. However, previous studies with some statins either did not alter insulin sensitivity or promoted insulin resistance despite significant improvements in endothelial dysfunction and decreases in circulating pro-inflammatory markers. This may be due to pleiotropic or off-target effects of some statins to cause insulin resistance by diverse mechanisms unrelated to endothelial dysfunction. Indeed, there is evidence of other differential metabolic actions of distinct statins including effects on hydroxymethylglutaryl-CoA reductase inhibition, isoprotenoid synthesis, calcium release, glucose transport, insulin secretion, and/or insulin resistance. Pravastatin increases expression of adiponectin mRNA, enhances adiponectin secretion, increases plasma levels of adiponectin, and enhances insulin sensitivity in mice and humans. Clinical studies including large scale randomized controlled trials demonstrate potential differences between individual statins, with pravastatin promoting risk reduction for new onset of diabetes. Conversely, other statins including atorvastatin, rosuvastatin, and simvastatin all promote significant increase in this risk. Given the frequent concordance of metabolic diseases including diabetes, obesity, and metabolic syndrome with cardiovascular diseases associated with hyperlipidemia, it is important to understand the potential metabolic risks and benefits of therapies with distinct statins. In this review, we discuss these differential effects of statins on metabolic homeostasis and insulin sensitivity.

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Statin treatment has been reported to impair insulin sensitivity and increase type 2 diabetes prevalence, with lipophilic statins having a stronger effect than hydrophilic statins.
“Recently, it has been reported that statin treatment impairs insulin sensitivity and increases the prevalence of type 2 diabetes (19 -22); and it seems that lipophilic statins (i.e., simvastatin, atorvastatin, fluvastatin, lovastatin) have a more pronounced effect on insulin sensitivity compared with hydrophilic statins (i.e., pravastatin, rosuvastatin) (23).”
From Simvastatin Effects on Skeletal Muscle (2013) · cites this paper as [23]

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Statins and Risk of Diabetes
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A randomized trial evaluating the efficacy and safety of alirocumab in South Korea and Taiwan (ODYSSEY KT)
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Time‐ and Dose‐Dependent Association of Statin Use With Risk of Clinically Relevant New‐Onset Diabetes Mellitus in Primary Prevention: A Nationwide Observational Cohort Study
Ko, M. J., Jo, A. J., Kim, Y. J., Kang, S. H., Cho, S., Jo, S., Park, C., Yun, S., Lee, W. J., & Park, D. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.118.011320 · Cited by 63 · see citing works
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Primordial Drivers of Diabetes Heart Disease: Comprehensive Insights into Insulin Resistance
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Lipid-lowering Therapies, Glucose Control and Incident Diabetes: Evidence, Mechanisms and Clinical Implications
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Antioxidant Effects of Statins in the Management of Cardiometabolic Disorders
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Intensity of Statin Therapy, Achieved Low-Density Lipoprotein Cholesterol Levels and Cardiovascular Outcomes in Japanese Patients After Coronary Revascularization: – Perspectives From the CREDO-Kyoto Registry Cohort-2 –
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Differential Effects of Atorvastatin and Pitavastatin on Inflammation, Insulin Resistance, and the Carotid Intima-Media Thickness in Patients with Dyslipidemia
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Statin therapy with or without ezetimibe and the progression to diabetes
Barkas, F., Elisaf, M., Liberopoulos, E. N., Klouras, E., Liamis, G. L., & Rizos, E. C. (2015) · Journal of clinical lipidology · doi:10.1016/j.jacl.2015.11.015 · Cited by 39 · see citing works
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The apoB/apoA-I Ratio is a Strong Predictor of Cardiovascular Risk
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Potentially important considerations in choosing specific statin treatments to reduce overall morbidity and mortality
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Differential Impact of Statin on New-Onset Diabetes in Different Age Groups: A Population-Based Case-Control Study in Women from an Asian Country
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The Risk of Hepatotoxicity, New Onset Diabetes and Rhabdomyolysis in the Era of High-Intensity Statin Therapy: Does Statin Type Matter?
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Is Atorvastatin Associated with New Onset Diabetes or Deterioration of Glycemic Control? Systematic Review Using Data from 1.9 Million Patients
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Rosuvastatin Prevents the Exacerbation of Atherosclerosis in Ligature-Induced Periodontal Disease Mouse Model
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Rosuvastatin Treatment Affects Both Basal and Glucose-Induced Insulin Secretion in INS-1 832/13 Cells
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Navarese, E. P., Szczesniak, A. M., Kołodziejczak, M. M., Górny, B., Kubica, J., & Suryapranata, H. (2013) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-013-0053-0 · Cited by 32 · see citing works
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Impact of statins on risk of new onset diabetes mellitus: a population-based cohort study using the Korean National Health Insurance claims database
Lee, J., Noh, Y., Shin, S., Lim, H., Park, R. W., Bae, S. K., Oh, E., Kim, G. J., Kim, J. H., & Lee, S. (2016) · Therapeutics and Clinical Risk Management · doi:10.2147/tcrm.s117150 · Cited by 31 · see citing works
Statins and New-Onset Diabetes
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Combination Pravastatin and Valsartan Treatment Has Additive Beneficial Effects to Simultaneously Improve Both Metabolic and Cardiovascular Phenotypes Beyond That of Monotherapy With Either Drug in Patients With Primary Hypercholesterolemia
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Modulation of H 2 S Metabolism by Statins: A New Aspect of Cardiovascular Pharmacology
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Rosuvastatin and Atorvastatin: Comparative Effects on Glucose Metabolism in Non-Diabetic Patients with Dyslipidaemia
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Lipid-lowering therapy and lipid goal attainment in patients with metabolic syndrome in China: Subgroup analysis of the Dyslipidemia International Study-China (DYSIS-China)
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Differential Metabolic Actions of Specific Statins: Clinical and Therapeutic Considerations
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Statins and vein graft failure in coronary bypass surgery
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Fenofibrate plus simvastatin (fixed-dose combination) for the treatment of dyslipidaemia
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Caveats to aggressive lowering of lipids by specific statins
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Combining Potent Statin Therapy with Other Drugs to Optimize Simultaneous Cardiovascular and Metabolic Benefits while Minimizing Adverse Events
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Impact of low dose atorvastatin on development of new-onset diabetes mellitus in Asian population: Three-year clinical outcomes
Park, J. Y., Rha, S., Choi, B. G., Choi, J. W., Ryu, S. K., Kim, S., Noh, Y., Choi, S. Y., Akkala, R. G., Hu, L., et al. (2015) · International Journal of Cardiology · doi:10.1016/j.ijcard.2015.03.047 · Cited by 23 · see citing works
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Rosuvastatin dose-dependently improves flow-mediated dilation, but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients
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Opposite effects of pravastatin and atorvastatin on insulin sensitivity in the rat: Role of vitamin D metabolites
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Prolonged Exposure to Insulin Induces Mitochondrion-Derived Oxidative Stress through Increasing Mitochondrial Cholesterol Content in Hepatocytes
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BMP-9 enhances fibroblast growth factor 21 expression and suppresses obesity
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Simvastatin-Induced Insulin Resistance May Be Linked to Decreased Lipid Uptake and Lipid Synthesis in Human Skeletal Muscle: the LIFESTAT Study
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Diabetogenic effects of cardioprotective drugs
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Effects of combining simvastatin with rosiglitazone on inflammation, oxidant stress and ambulatory blood pressure in patients with the metabolic syndrome: the SIROCO study
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Rosuvastatin limits the activation of hepatic stellate cells in diet‐induced obese mice
Marinho, T. D. S., Kawasaki, A., Bryntesson, M., Souza‐Mello, V., Barbosa‐da‐Silva, S., Águila, M. B., & Mandarim‐de‐Lacerda, C. A. (2016) · Hepatology Research · doi:10.1111/hepr.12821 · Cited by 20 · see citing works
Diabetogenic Effect of Statins: A Double-Edged Sword?
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Cardiometabolic comorbidity in antipsychotic treated patients: need for systematic evaluation and treatment
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Low-dose oral cyclophosphamide therapy reduces atherosclerosis progression by decreasing inflammatory cells in a murine model of atherosclerosis
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Does Adjuvant Treatment With Ginkgo Biloba to Statins Have Additional Benefits in Patients With Dyslipidemia?
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High-Dose Statin Therapy Does Not Induce Insulin Resistance in Patients with Familial Hypercholesterolemia
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Statin-induced Myopathy in Skeletal Muscle: the Role of Exercise
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Clinical Perspectives on Targeting Therapies for Personalized Medicine
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Statin Intake Is Associated With Decreased Insulin Sensitivity During Cardiac Surgery
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Statin Adverse Events in Primary Prevention: Between Randomized Trials and Observational Studies
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The differences in the incidence of diabetes mellitus and prediabetes according to the type of HMG‐CoA reductase inhibitors prescribed in Korean patients
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The Antinociceptive Effects of Rosuvastatin in Chronic Constriction Injury Model of Male Rats
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Lipid-Lowering Drugs and Circulating Adiponectin
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Nanotherapeutics Containing Lithocholic Acid-Based Amphiphilic Scorpion-Like Macromolecules Reduce In Vitro Inflammation in Macrophages: Implications for Atherosclerosis
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Differential metabolic effects of pravastatin and simvastatin in hypercholesterolemic patients
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Self-citation
Differential metabolic effects of rosuvastatin and pravastatin in hypercholesterolemic patients
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Effects of simvastatin therapy on circulating adipocytokines in patients with hypercholesterolemia
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Self-citation

Authors: Koh, K. K., Sakuma, I., & Quon, M. J.
Affiliations: Gachon University Gil Medical Center (KR)
Hokko Memorial Hospital (JP)
National Institutes of Health (US)
Corresponding author: Koh, Kwang Kon
ORCID: Koh, Kwang Kon
Sakuma, Ichiro
Quon, Michael J.
Venue: Atherosclerosis
Publisher: Elsevier BV
Published: 2011-03
Volume: 215
Issue: 1
Pages: 1-8
ISSN: 0021-9150 (ISSN-L)
DOI: 10.1016/j.atherosclerosis.2010.10.036
OpenAlex: W2062685715
Cited by: 130
References: 76
Citations by year: 2026: 3 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 1 · 2021: 1 · 2020: 5 · 2019: 5 · 2018: 8 · 2017: 9 · 2016: 12 · 2015: 12 · 2014: 17 · 2013: 16 · 2012: 21
FWCI: 2.73
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Atherosclerosis (publishedVersion)
PubMed (publishedVersion)
Funders: Gachon University Gil Hospital
Intramural Research Program
National Center for Complementary and Alternative Medicine
National Institutes of Health
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords: statins, insulin resistance, insulin sensitivity, pravastatin, atorvastatin, rosuvastatin, simvastatin, adiponectin, endothelial dysfunction, diabetes risk, metabolic syndrome, HMG-CoA reductase inhibition, glucose transport, insulin secretion, pleiotropy
MeSH terms: Rosuvastatin Calcium, Atorvastatin, Animals, Clinical Trials as Topic, Diabetes Mellitus, Type 2, Fluorobenzenes, Heptanoic Acids, Homeostasis, Humans, Hydroxymethylglutaryl CoA Reductases, Insulin Resistance, Pyrimidines, Pyrroles, Sulfonamides, Pravastatin, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Simvastatin, Mice, Adiponectin

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Differential metabolic effects of distinct statins

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