REVIEW Future perspectives on glucagon-like peptide-1, diabetes and cardiovascular risk E. Mannucci a, *, C.M. Rotella b a Sections of Diabetes and Metabolic Diseases, Geriatric Unit, University of Florence, Italy b Sections of Diabetes and Metabolic Diseases, Endocrine Unit, University of Florence, Italy Received 20 May 2008; received in revised form 12 July 2008; accepted 7 August 2008 KEYWORDS Glucagon-like peptide-1; Dipeptidyl-peptidase-4; Cardiovascular risk factors; Cardiovascular disease; Hypoglycemic drugs; Type 2 diabetes Abstract Aims: Glucagon-like peptide-1 (GLP-1), a gastrointestinal hormone mainly produced in the post-prandial state, reduces blood glucose through the stimulation of insulin secretion and the inhibition of glucagon release. Long-acting GLP-1 receptor agonists, and dipeptidyl-peptidase-4 (DPP-4) inhibitors which increase GLP-1 levels, are used as hypogly- cemic treatments in type 2 diabetes. This paper aims at reviewing the potential benefit of those treatments in the prevention of cardiovascular risk in type 2 diabetic patients. Data synthesis: Experimental studies have shown that GLP-1 has several potentially beneficial actions on cardiovascular risk. Some of those, such as protection from myocardial ischemic damage and improvement of cardiac function, have also been demonstrated in humans. However, the equivalence of GLP-1 agonists and DPP-4 inhibitors with GLP-1, with respect to cardiovascular risk profile, cannot be assumed or taken for granted. Drugs of those two classes have been shown to effectively reduce glycated hemoglobin and to have a specific effect on post-prandial glucose; furthermore, they seem to reduce blood pressure and to have some favorable effects on lipid profiles. Additionally, GLP-1 agonists induce weight loss in diabetic patients. Conclusion: The profile of action of GLP-1 receptor agonists and DPP-4 inhibitors suggests the possibility of an actual reduction in cardiovascular risk, which needs to be confirmed by large long-term clinical trials. ª 2008 Elsevier B.V. All rights reserved. The concept of ‘‘incretins’’, i.e. hormones produced after meal ingestion which stimulate insulin secretion, has been postulated for a long time by experiments suggesting that substances derived from the upper part of the small * Corresponding author. Day Hospital Diabetologico Ponte Nuovo, Azienda Ospedaliero-Universitaria Careggi, Via delle Oblate 4, 50131 Firenze, Italy. Tel.: þ39 055 7949742; fax: þ39 055 7949660. E-mail address: edoardo.mannucci@unifi.it (E. Mannucci). 0939-4753/$ - see front matter ª 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.numecd.2008.08.002 available at www.sciencedirect.com journal homepage: www.elsevier.com/locate/nmcd Nutrition, Metabolism & Cardiovascular Diseases (2008) 18, 639e645