Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years

Klonoff, David C.; Buse, John B.; Nielsen, Loretta L.; Guan, Xiaodan; Bowlus, Christopher L.; Holcombe, John H.; Wintle, Matthew; Maggs, David

doi:10.1185/030079907x253870

Cited by 428 publications

(493 citation statements)

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“…It was suggested that the increase in cardiac output may be a compensatory response to vasodilatation elsewhere. The effectiveness of GLP-1R agonists in reducing BP in clinical trials of type 2 diabetes and obesity is most evident in individuals with higher baseline BP [1,5,6] and may be attributable to reductions in tubular sodium reabsorption [32] or central sympathetic output [33] as well as peripheral vasodilatory effects [34]. In contrast to findings in rodents [35], GLP-1 and GLP-1R agonists do not appear to promote the secretion of atrial natriuretic peptide in humans [30,31].…”

Section: Discussioncontrasting

confidence: 39%

“…Phase 3 studies focusing on the blood-glucose-lowering effects of GLP-1 agonists indicate durable, modest reductions in systolic and, less consistently, diastolic blood pressure (BP), and a slight rise in heart rate (HR) [4][5][6][7]. Postprandial hypotension (PPH), defined as a fall in systolic BP ≥20 mmHg within 2 h of a meal [8], is a common disorder, associated with substantial morbidity and increased mortality [9], for which current management is suboptimal [10].…”

Section: Introductionmentioning

confidence: 99%

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Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

et al. 2015

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Aims/hypothesis A postprandial fall in BP occurs frequently in older individuals and in patients with type 2 diabetes. The magnitude of this decrease in BP is related to the rate of gastric emptying (GE). Intravenous administration of glucagon-like peptide-1 (GLP-1) attenuates the hypotensive response to intraduodenal glucose in healthy older individuals. We sought to determine the effects of exogenous GLP-1 on BP, GE, superior mesenteric artery (SMA) flow and glycaemic response to oral ingestion of glucose in healthy older individuals and patients with type 2 diabetes. Methods Fourteen older volunteers (six men, eight women; age 72.1±1.1 years) and ten patients with type 2 diabetes (six men, four women; age 68.7±3.4 years; HbA 1c 6.6±0.2% [48.5± 2.0 mmol/mol]; nine with blood glucose managed with metformin, two with a sulfonylurea and one with a dipeptidyl-peptidase 4 inhibitor) received an i.v. infusion of GLP-1 (0.9 pmol kg −1 min −1 ) or saline (154 mmol/l NaCl) for 150 min (t=−30 min to t= 120 min) in randomised order. At t=0 min, volunteers consumed a radiolabelled 75 g glucose drink. BP was assessed with an automated device, GE by scintigraphy and SMA flow by ultrasonography. Blood glucose and serum insulin were measured. Results GLP-1 attenuated the fall in diastolic BP after the glucose drink in older individuals (p<0.05) and attenuated the fall in systolic and diastolic BP in patients with type 2 diabetes (p<0.05). GE was faster in patients with type 2 diabetes than in healthy individuals (p<0.05). In both groups, individuals had slower GE (p<0.001), decreased SMA flow (p<0.05) and a lower degree of glycaemia (p<0.001) when receiving GLP-1. Conclusions/interpretation Intravenous GLP-1 attenuates the hypotensive response to orally administered glucose and decreases SMA flow, probably by slowing GE. GLP-1 and 'short-acting' GLP-1 agonists may be useful in the management of postprandial hypotension.

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Section: Discussioncontrasting

confidence: 39%

Section: Introductionmentioning

confidence: 99%

Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

et al. 2015

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“…Of particular interest has been whether GLP-1 based therapy improves cardiovascular function. Up to now, clinically important markers for cardiovascular events, such as blood lipids and blood pressure have been shown to be improved by GLP-1 based therapy [13,36]. What 13 is now important is to perform long-term studies on cardiovascular events to examine whether GLP-1 based therapy improves cardiovascular outcomes.…”

Section: Mechanisms Of Glp-1 Receptor Agonists and Dpp-4 Inhibitorsmentioning

confidence: 99%

GLP-1 for type 2 diabetes

Åhrén

2011

Experimental Cell Research

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Glucagon-like peptide-1 (GLP-1)-based therapy of type 2 diabetes is executed either by GLP-1 receptor agonists, which stimulate the GLP-1 receptors, or by dipeptidyl peptidase-4 (DPP-4) inhibitors, which prevent the inactivation of endogenous GLP-1 thereby increasing the concentration of endogenous active GLP-1. GLP-1 activates pancreatic receptors resulting in improved glycemia through glucose-dependent stimulation of insulin secretion and inhibition of glucagon secretion. There is also a potential beta cell preservation effect, as judged from rodent studies. GLP-1 receptors are additionally expressed in extrapancreatic tissue, having potential for the treatment to reduce body weight and to potentially have beneficial cardio-and endothelioprotective effects. Clinical trials in subjects with type 2 diabetes have shown that in periods of 12 weeks or more, these treatments reduce HbA 1c by ≈0.8-1.1% from baseline levels of 7.7-8.5%, and they are efficient both as monotherapy and in combination therapy with metformin, sulfonylureas, thiazolidinediones or insulin. Furthermore, GLP-1 receptor agonists reduce body weight, whereas DPP-4 inhibitors are body weight neutral. The treatment is safe with very low risk for adverse events, including hypoglycaemia. GLP-1 based therapy is thus a novel and now well established therapy of type 2 diabetes, with a particular value in combination with metformin in patients who are inadequately controlled by metformin alone.

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“…However, circulating GLP-1 has a very short half-life due to inactivation by the enzyme dipeptidyl peptidase IV (DPP-4). The potential of GLP-1 for the treatment of diabetes has led to the development of long-acting DPPIVresistant GLP-1 analogs and orally bioavailable DPP-4 inhibitors, both approaches having proven efficacy in lowering blood glucose levels and HbA 1c in patients with type 2 diabetes 14,18 .…”

Section: Introductionmentioning

confidence: 99%

PPARβ/δ Activation Induces Enteroendocrine L Cell GLP-1 Production

et al. 2011

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Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years

Abstract: Adjunctive exenatide treatment for > or = 3 years in T2DM patients resulted in sustained improvements in glycemic control, cardiovascular risk factors, and hepatic biomarkers, coupled with progressive weight reduction.

Cited by 428 publications

References 0 publications

Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes

GLP-1 for type 2 diabetes

PPARβ/δ Activation Induces Enteroendocrine L Cell GLP-1 Production

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