Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes

Linnebjerg, Helle; Park, Sumin; Kothare, Prajakti A.; Trautmann, Michael E.; Mace, Kenneth F.; Fineman, Mark; Wilding, Ian R.; Nauck, Michael A.; Horowitz, Michael

doi:10.1016/j.regpep.2008.07.003

Cited by 215 publications

(213 citation statements)

References 32 publications

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“…The principal effects of GLP‐1 receptor agonists are to induce pancreatic insulin secretion, slow gastric emptying, and suppress postprandial glucagon secretion 15, 34, 35, 36, 37. Since increases in t max and t 1/2b of the gastric emptying rate were observed in the lixisenatide group vs the sitagliptin group, it is likely that slowing of gastric emptying was the driver for PPG reduction in this study, rather than insulinotropic effects.…”

Section: Discussionmentioning

confidence: 82%

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

Yamada

Senda

Naito

et al. 2017

Diabetes Obesity Metabolism

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AimTo evaluate the pharmacodynamics of lixisenatide once daily vs sitagliptin once daily in Japanese patients with type 2 diabetes receiving insulin glargine U100.Materials and methodsThis multicentre, open‐label, phase IV study (NEXTAGE Study; ClinicalTrials.gov number, NCT02200991) randomly assigned 136 patients to either lixisenatide once daily via subcutaneous injection (10 µg initially increased weekly by 5 up to 20 µg) or once‐daily oral sitagliptin 50 mg. The primary endpoint was the change in postprandial glucose (PPG) exposure 4 hours after a standardized breakfast (PPG area under the plasma glucose concentration–time curve [AUC0 :00‐4:00h]) from baseline to day 29.ResultsLixisenatide reduced PPG exposure to a statistically significantly greater extent than sitagliptin: least squares (LS) mean change from baseline in PPG AUC0 :00‐4:00h was −347.3 h·mg/dL (−19.3 h·mmol/L) in the lixisenatide group and −113.3 h·mg/dL (−6.3 h·mmol/L) in the sitagliptin group (LS mean between‐group difference −234.0 h·mg/dL [−13.0 h·mmol/L], 95% confidence interval −285.02 to −183.00 h·mg/dL [−15.8 to −10.2 h·mmol/L]; P < .0001). Lixisenatide led to significantly greater LS mean reductions in maximum PPG excursion than sitagliptin (−122.4 vs −46.6 mg/dL [−6.8 vs −2.6 h·mmol/L]; P < .0001). Change‐from‐baseline reductions in exposure to C‐peptide, fasting glycoalbumin levels, and the gastric emptying rate were greater in the lixisenatide than in the sitagliptin group. The incidence of treatment‐emergent adverse events was higher with lixisenatide (60.9%) than with sitagliptin (16.4%), with no serious events or severe hypoglycaemia reported.ConclusionLixisenatide reduced PPG significantly more than sitagliptin, when these agents were added to basal insulin glargine U100, and was well tolerated.

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Section: Discussionmentioning

confidence: 82%

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

Yamada

Senda

Naito

et al. 2017

Diabetes Obesity Metabolism

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“…In health, endogenous GLP-1 slows gastric emptying 6 , while exogenous GLP-1 at pharmacological doses slows gastric emptying substantially in health, type 2 diabetes and critical illness, leading to a reduction in postprandial glycaemic excursions 14,15 . The magnitude of the effects are dependent on the baseline rate of gastric emptying, such that GLP-1 has little, if any effect when gastric emptying is already delayed [14][15][16] . However, there is no information in adult critically ill patients about fasting or nutrient stimulated plasma GLP-1 concentrations and their relationship to gastric emptying.…”

Section: Introductionmentioning

confidence: 99%

Endogenous amylin and glucagon-like peptide-1 concentrations are not associated with gastric emptying in critical illness

Summers

Bartolomeo

Zaknic

et al. 2014

Acta Anaesthesiol Scand

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“…Accordingly, in healthy patients and in those with type 2 diabetes, postprandial insulin concentrations are suppressed, rather than stimulated, during GLP-1 administration (7,9). The magnitude of the deceleration of gastric emptying induced by exogenous GLP-1 and its agonists is dependent on the baseline rate of gastric emptying, so that the emptying rate is markedly slowed in those with relatively rapid gastric emptying before GLP-1 administration, whereas the rate is largely unaffected when gastric emptying is already delayed at baseline (10,11). Furthermore, the reduction in postprandial glycemia induced by these agents is closely related to the magnitude of the slowing of gastric emptying (9)(10)(11).…”

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confidence: 99%

Hyperglycemia Potentiates the Slowing of Gastric Emptying Induced by Exogenous GLP-1

et al. 2015

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OBJECTIVEAcute hyperglycemia markedly slows gastric emptying. Exogenous GLP-1 also slows gastric emptying, leading to diminished glycemic excursions. The primary objective was to determine whether hyperglycemia potentiates the slowing of gastric emptying induced by GLP-1 administration. RESEARCH DESIGN AND METHODSTen healthy participants were studied on 4 separate days. Blood glucose was clamped at hyperglycemia using an intravenous infusion of 25% dextrose (∼12 mmol/L; hyper) on 2 days, or maintained at euglycemia (∼6 mmol/L; eu) on 2 days, between t = 215 and 240 min. During hyperglycemic and euglycemic days, participants received intravenous GLP-1 (1.2 pmol/kg/min) and placebo in a randomized double-blind fashion. At t = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq technetium-99m-sulfur colloid and 3 g 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from t = 0 to 240 min and serum 3-OMG taken at regular intervals from t = 15 to 240 min. The areas under the curve for gastric emptying and 3-OMG were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests. RESULTSHyperglycemia slowed gastric emptying (eu/placebo vs. hyper/placebo; P < 0.001) as did GLP-1 (eu/placebo vs. eu/GLP-1; P < 0.001). There was an additive effect of GLP-1 and hyperglycemia, such that gastric emptying was markedly slower compared with GLP-1 administration during euglycemia (eu/GLP-1 vs. hyper/GLP-1; P < 0.01). CONCLUSIONSAcute administration of exogenous GLP-1 profoundly slows gastric emptying during hyperglycemia in excess of the slowing induced by GLP-1 during euglycemia. Studies are required to determine the effects of hyperglycemia on gastric emptying with the subcutaneously administered commercially available GLP-1 agonists in patients with type 2 diabetes.Gastric emptying is a major determinant of postprandial glycemia in health, as well as in type 1 and type 2 diabetes (1,2), and accounts for ;35% of the variance in the initial glycemic response to oral carbohydrate (1). Accordingly, dietary and pharmacological strategies that slow gastric emptying, including short-acting GLP-1 agonists, are useful interventions to attenuate postprandial glycemic excursions and overall glycemia in type 2 diabetes (3).

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Effect of exenatide on gastric emptying and relationship to postprandial glycemia in type 2 diabetes

Cited by 215 publications

References 32 publications

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

Endogenous amylin and glucagon-like peptide-1 concentrations are not associated with gastric emptying in critical illness

Hyperglycemia Potentiates the Slowing of Gastric Emptying Induced by Exogenous GLP-1

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