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Incretin-based therapies for treatment of postprandial dyslipidemia in insulin-resistant states

Farr, Sarah; Adeli, Khosrow

doi: 10.1097/MOL.0b013e32834d68f0
NUTRITION AND METABOLISM: Edited by Paul Nestel and Ronald P. Mensink

Purpose of review In prediabetes and diabetes, hyperglycemia is often accompanied by fasting and postprandial hyperlipidemia. Incretin-based therapies are in increasing clinical use for treating hyperglycemia, but recent evidence emphasizes their ability to improve lipoprotein abnormalities. This is significant as heightened postprandial chylomicron levels during insulin resistance contribute to atherogenic diabetic dyslipidemia. This review summarises the evidence supporting a beneficial effect of incretin-based therapies on diabetic dyslipidemia through modulation of intestinal lipoprotein metabolism.

Recent findings Preclinical and clinical trials have involved administering dipeptidyl peptidase IV inhibitors and glucagon-like peptide-1 receptor (GLP-1R) agonists to healthy and insulin-resistant individuals. Results indicate that enhancing GLP-1R signalling decreases postprandial apoB48-containing triglyceride-rich lipoproteins. These effects may be direct or may be secondary to reduced gastric emptying, increased insulin secretion, or enhanced chylomicron clearance.

Summary Enhancing GLP-1R activity improves intestinal lipoprotein metabolism. GLP-1-mediated control of postprandial chylomicron production may be lost in type 2 diabetes in which the incretin response is impaired and in which associated dyslipidemia involves an excess of atherogenic chylomicron remnants. Further human studies are needed to better establish the impact of incretin-based therapies on dyslipidemia, as this offers a major new therapeutic approach to reduce cardiovascular risk in type 2 diabetic patients.

Molecular Structure and Function Research Institute, the Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

Correspondence to Khosrow Adeli, Molecular Structure and Function, Research Institute, the Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON M5G 1X8, Canada.Tel: +1 416 813 8682; fax: +1 416 813 6257; e-mail: khosrow.adeli@sickkids.ca

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