Gastric Emptying in Patients With Well-Controlled Type 2 Diabetes Compared With Young and Older Control Subjects Without Diabetes

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Aims: To evaluate the effects of 8 weeks' administration of exenatide (EXE) once weekly on gastric emptying of solids and liquids (using the "gold standard" technique, scintigraphy), glucose absorption and postprandial glycaemia in healthy people.Material and methods: A total of 32 healthy participants were randomized to receive either EXE once weekly (2 mg/wk subcutaneously; six men, 10 women, mean age 59.9 ± 0.9 years, mean body mass index [BMI] 29.6 ± 0.6 kg/m 2 ) or matching placebo (PBO; six men, 10 women, mean age 60.6 ± 1.2 years, mean BMI 29.5 ± 1.0 kg/m 2 ) for 8 weeks. Gastric emptying, nausea (visual analogue scale), and plasma glucose, insulin, C-peptide and glucagon were measured for 120 min after a solid/liquid meal, comprising 100 g ground beef (radiolabelled with 20 MBq 99m Tc-sulphur colloid) and 150 mL 10% glucose (radiolabelled with 7 MBq 67 Ga-EDTA), and containing 5 g 3-Omethyl-glucose (3-OMG) as a marker of glucose absorption, at baseline and after 8 weeks' treatment. Results:The study treatments were well tolerated. Scores for nausea were consistently low, with no difference between the EXE once weekly and PBO groups. EXE once weekly slowed gastric emptying of solids (area under the curve [AUC] 0-120min : P < 0.05) and liquids (AUC 0-120min : P = 0.01) substantially, and attenuated glucose absorption (3-OMG incremental AUC [iAUC] 0-30min : P = 0.001) and the postprandial rise in plasma glucose (iAUC 0-30min : P = 0.008). Plasma glucagon at 2 h was reduced by EXE once weekly (P = 0.001). The magnitude of the reduction in plasma glucose at t = 30 min from baseline to 8 weeks with EXE once weekly was related inversely to the 50% emptying time of the glucose drink (r = −0.55, P = 0.03). Conclusions:In healthy participants, 8 weeks' administration of the "long-acting" glucagon-like peptide-1 receptor agonist EXE, slowed gastric emptying of solids and liquids substantially, with consequent reductions in glucose absorption and postprandial glycaemia.

Section: Discussionmentioning

confidence: 99%

Exenatide once weekly slows gastric emptying of solids and liquids in healthy, overweight people at steady‐state concentrations

Jones

Huynh

Hatzinikolas

et al. 2020

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“…Even relatively minor changes in GE may have a major impact on postprandial glycaemia . In people with uncomplicated T2DM, in whom GE is usually normal or accelerated, there is a close relationship between the blood glucose response to carbohydrate and GE . A number of dietary and pharmacological strategies have been developed to reduce postprandial glycaemia by slowing GE including the amylin agonist, pramlintide, and GLP‐1 receptor agonists (GLP‐1RAs) .…”

Section: Introductionmentioning

confidence: 99%

“…2 In people with uncomplicated T2DM, in whom GE is usually normal or accelerated, there is a close relationship between the blood glucose response to carbohydrate and GE. 3,4 A number of dietary and pharmacological strategies have been developed to reduce postprandial glycaemia by slowing GE 1 including the amylin agonist, pramlintide, and GLP-1 receptor agonists (GLP-1RAs). 1 While both exogenous 5 and endogenous 6 GLP-1 slow GE in healthy individuals, the effect of exogenous GLP-1 is attenuated markedly with continuous, as opposed to acute, or intermittent, exposure.…”

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confidence: 99%

Effects of sitagliptin on gastric emptying of, and the glycaemic and blood pressure responses to, a carbohydrate meal in type 2 diabetes

Stevens

Buttfield

et al. 2019

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Aims To determine the effects of the dipeptidyl peptidase‐4 inhibitor, sitagliptin, on gastric emptying (GE) of a high‐carbohydrate meal and associated glycaemic and blood pressure (BP) responses in type 2 diabetes mellitus (T2DM). Materials and Methods Fourteen patients with T2DM (nine men, five women; age 67.8 ± 1.5 years; body mass index 31.2 ± 0.9 kg/m2; T2DM duration: 4.2 ± 0.9 years; glycated haemoglobin: 46 ± 1.8 mmol/mol [6.4% ± 0.2%]), managed by diet and/or metformin, underwent concurrent measurements of GE, BP and plasma glucose for 240 minutes after ingestion of a radiolabelled mashed potato meal after receiving sitagliptin (100 mg) or placebo in randomized, double‐blind, crossover fashion on 2 consecutive days. Results Sitagliptin reduced postprandial plasma glucose (P < .005) without affecting GE (P = .88). The magnitude of the glucose‐lowering effect (change in incremental area under the curve0–240 min from placebo to sitagliptin) was related to GE (kcal/min) on placebo (r = 0.68, P = .008) There was a comparable fall in systolic BP (P = .80) following the meal, with no difference between the 2 days. Conclusions In T2DM, while sitagliptin has no effect on either GE or postprandial BP, its ability to lower postprandial glucose are dependent on the basal rate of GE.

“…In both studies, metformin was infused into the stomach in the absence of any nutrient, so the impact on postprandial blood glucose is unknown. Furthermore, small intestinal exposure to metformin may be confounded by the substantial difference in rates of gastric emptying between individuals . Accordingly, study designs where metformin is administered directly into the small intestine may allow more meaningful interpretation.…”

Section: Gastrointestinal Effects Of Metformin: Role Of Gut Peptidesmentioning

confidence: 99%

Mechanism of glucose‐lowering by metformin in type 2 diabetes: Role of bile acids

Sansome

Xie

Veedfald

et al. 2019

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Type 2 diabetes mellitus (T2DM) is an increasingly prevalent chronic condition, characterized by abnormally elevated blood glucose concentrations and, as a consequence, increased risk of micro‐ and macrovascular complications. Metformin is usually the first‐line glucose‐lowering medication in T2DM; however, despite being used for more than 60 years, the mechanism underlying the glucose‐lowering action of metformin remains incompletely understood. Although metformin reduces hepatic glucose production, there is persuasive evidence that the gastrointestinal tract is crucial in mediating this effect, particularly via secretion of the incretin hormone glucagon‐like peptide 1 (GLP‐1). It is now well recognized that bile acids, in addition to their established function in fat digestion and absorption, are important regulators of glucose metabolism. Exposure of the small and large intestine to bile acids induces GLP‐1 secretion, modulates the composition of the gut microbiota, and reduces postprandial blood glucose excursions in humans with and without T2DM. Metformin reduces intestinal bile acid resorption substantially, such that intraluminal bile acids may, at least in part, account for its glucose‐lowering effect. The present review focuses on the conceptual shift in our understanding as to how metformin lowers blood glucose in T2DM, with a particular emphasis on the role of intestinal bile acids.