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Lipid-lowering Therapies, Glucose Control and Incident Diabetes: Evidence, Mechanisms and Clinical Implications

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Abstract

Lipid-lowering therapies constitute an essential part in the treatment and prevention of cardiovascular diseases and are consistently shown to reduce adverse cardiovascular outcomes in wide-scale populations. Recently, there is increased awareness of the possibility that lipid-lowering drugs may affect glucose control and insulin resistance. This phenomenon is reported in all classes of lipid-modifying agents, with differential effects of distinct drugs. Since the prevalence of metabolic syndrome and diabetes is rising, and lipid-modifying therapies are widely used to reduce the cardiovascular burden in these populations, it is of importance to examine the relationship between lipid-lowering drugs, glycemic control and incident diabetes. In the current review we discuss the evidence, ranging from experimental studies to randomized controlled clinical trials and meta-analyses, of how lipid-modifying therapies affect glycemic control and insulin sensitivity. Cumulative data suggest that both statins and niacin are associated with increased risk of impaired glucose control and development of new-onset diabetes, as opposed to bile-acid sequestrants which display concomitant moderate lipid and glucose lowering effects, and fibrates (particularly the pan-PPAR agonist bezafibrate) which may produce beneficial effects on glucose metabolism and insulin sensitivity. Ezetimibe is implied to ameliorate metabolic markers such as hepatic steatosis and insulin resistance, with yet little support from clinical trials, while fish oils which in experimental studies produce favorable effects on insulin sensitivity, although studied extensively, continue to show inconclusive effects on glucose homeostasis in patients with diabetes. Suggested mechanisms of how lipid-modifying agents affect glucose control and their clinical implications in this context, are summarized.

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Abbreviations

BAS:

bile acids sequestrants

CETP:

Cholesteryl ester transfer protein

CI:

confidence interval

FPG:

fasting plasma glucose

FXR:

farnesoid X receptor

GLP-1:

glucagon-like peptide-1

HDL-C:

high-density lipoprotein cholesterol

HgbA1c:

glycosylated hemoglobin

LDL-C:

low-density lipoprotein cholesterol

n-3 PUFA:

omega-3 poly-unsaturated fatty acids

PPAR:

peroxisome proliferator-activated receptor

RR:

relative risk

TGR5:

G protein coupled bile acid receptor 1 (TGR5/GPBAR1)

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  1. Department of Cardiovascular Medicine, Lady Davis Carmel Medical Center, 7 Michal st., Haifa, Israel

    Barak Zafrir

  2. Department of Medicine and Pharmacology, Institute of Metabolomics Medicine, University of California, San Diego, USA

    Mohit Jain

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Zafrir, B., Jain, M. Lipid-lowering Therapies, Glucose Control and Incident Diabetes: Evidence, Mechanisms and Clinical Implications. Cardiovasc Drugs Ther 28, 361–377 (2014). https://doi.org/10.1007/s10557-014-6534-9

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