GLP-1 agonist-based therapies: An emerging new class of antidiabetic drug with potential cardioprotective effects

Sulistio, Melanie S.; Carothers, Curtis; Mangat, Mandeep; Lujan, Mike; Oliveros, Rene A; Chilton, Robert

doi:10.1007/s11883-009-0015-9

Cited by 23 publications

(21 citation statements)

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“…It may therefore also be considered, unless heart failure is present [60]. In very preliminary reports, therapy with GLP-1 receptor agonists and DPP-4 inhibitors has been associated with improvement in either cardiovascular risk or risk factors, but there are no long-term data regarding clinical outcomes [113]. There are very limited data suggesting that AGIs [114] and bromocriptine [115] may reduce cardiovascular events.…”

Section: Comorbiditiesmentioning

confidence: 99%

Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

et al. 2012

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Section: Comorbiditiesmentioning

confidence: 99%

Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

et al. 2012

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“…60 In very preliminary reports, therapy with GLP-1 receptor agonists and DPP-4 inhibitors has been associated with improvement in either cardiovascular risk or risk factors, but there are no long-term data regarding clinical outcomes. 113 There are very limited data suggesting that AGIs 114 and bromocriptine 115 may reduce cardiovascular events. Heart failure.…”

Section: Comorbiditiesmentioning

confidence: 99%

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

et al. 2012

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“…GLP-1 receptor agonists appear to have CV effects independent of the autonomic nervous system, and even independent of known GLP-1 receptor-linked pathways [97]. Preclinical evidence suggests a novel two-pathway schema for the CV actions of GLP-1.…”

Section: Extrapancreatic Effects Of Glp-1: Cardiovascular Tissue Adimentioning

confidence: 98%

“…In a recent study, GLP-1-receptor activation improved survival after myocardial infarction (MI) in the normal and diabetic mouse heart. This finding suggests that GLP-1-receptor activation is accompanied by effects on the modulation of mediators important for cardiomyocyte survival, including peroxisome proliferator-activated receptors (PPAR)-β/δ, heme oxygenase (HO)-1, Akt, and glycogen synthase kinase (GSK)-3β [96].GLP-1 receptor agonists appear to have CV effects independent of the autonomic nervous system, and even independent of known GLP-1 receptor-linked pathways [97]. Preclinical evidence suggests a novel two-pathway schema for the CV actions of GLP-1.…”

mentioning

confidence: 99%

Preclinical and Clinical Data on Extraglycemic Effects of GLP-1 Receptor Agonists

Gallwitz¹

2009

Rev Diabet Stud

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■ AbstractThe diverse actions of the incretin hormone glucagon-like peptide (GLP)-1 include insulinotropic, beta-cell preservative, cardioprotective and vasodilatory effects. This spectrum makes GLP-1 an appealing therapeutic option for patients with type 2 diabetes. However, its rapid metabolism by the enzyme dipeptidyl peptidase (DPP)-4 renders it impractical. Incretin-based analogues have been developed to extend endogenous GLP-1 action (GLP-1 receptor agonists) and to hamper its degradation (DPP-4 inhibitors). Evidence suggests that GLP-1 receptor agonists and DPP-4 inhibitors have different pharmacodynamic and pharmacokinetic effects. For example, GLP-1 receptor agonists deliver supraphysiologic levels of GLP-1 analogues designed to resist inactivation by DPP-4, whereas DPP-4 inhibition conserves native GLP-1 resulting in concentrations within the physiologic range. Furthermore, GLP-1 receptor agonists induce glucose-dependent insulin secretion, beta-cell protection, and other extraglycemic benefits such as weight loss and improvement in markers of cardiovascular risk. In contrast, DPP-4 inhibitors are weight neutral and have modest effects on glucose control. DPP-4 inhibition is dependent on the availability of endogenous GLP-1, which appears to be adversely affected by type 2 diabetes and its progression. Therefore, DPP-4 inhibitors may be better suited for patients with mild hyperglycemia without comorbidities. This review examines the present understanding of the pancreatic effects of endogenous GLP-1, and the extrapancreatic actions it exerts on human bodily systems. Also, it analyzes available preclinical and clinical data on incretin therapies with respect to glycemia, lipids, blood pressure, and weight.Keywords: type 2 diabetes · beta-cell · DPP-4 inhibitors · extrapancreatic effects · incretin · weight loss · glycemia · insulinotropic polypeptide Introduction lucagon-like peptide 1 (GLP-1) was first characterized as an incretin hormone. In the years after its discovery, diverse actions of GLP-1 were described. These include: 1. insulinotropic effects [1, 2], 2. neogenesis, differentiation, and preservation of pancreatic β-cells [3][4][5][6][7], and 3. cardioprotective and vasodilatory properties. The discrete mechanisms governing the latter two effects have not yet been fully clarified [8]. Despite early encouraging results with intravenous infusion [9][10][11], native GLP-1 was determined to be an impractical therapeutic tool, due to its rapid extensive metabolism by dipeptidyl peptidase 4 (DPP-4) [12, 13]. Consequently, attempts to adapt GLP-1 to therapeutic advantages in the treatment of type 2 diabetes resulted in the development of GLP-1 analogues that protract endogenous GLP-1 action. Also, DPP-4 inhibitors have been developed to impede the enzymatic inactivation of the incretin hormone.Current evidence suggests that GLP-1 receptor agonists and DPP-4 inhibitors have differential pharmacodynamic and pharmacokinetic effects. GLP-1 receptor agonists deliver supraphysiologic Reprint fromThe Revie...

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GLP-1 agonist-based therapies: An emerging new class of antidiabetic drug with potential cardioprotective effects

Cited by 23 publications

References 50 publications

Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Management of Hyperglycemia in Type 2 Diabetes: A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD)

Preclinical and Clinical Data on Extraglycemic Effects of GLP-1 Receptor Agonists

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