Liraglutide: short‐lived effect on gastric emptying—long lasting effects on body weight

Jelsing, Jacob; Vrang, Niels; Hansen, Gitte; Raun, Kirsten; Tang-Christensen, Mads; Knudsen, Lotte Bjerre

doi:10.1111/j.1463-1326.2012.01557.x

Cited by 154 publications

(152 citation statements)

References 48 publications

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“…Liraglutide has a half life of 13 hours, and is therefore dosed once daily without regard to meals. A rodent study suggests that the effect of liraglutide to slow gastric emptying is not sustained over time, and that regulation of appetite signals in the brain is the main mechanism for liraglutide induced weight loss [38]. In contrast, this study showed that gastric emptying is slowed for a longer period of time with exenatide, suggesting that this mechanism may be more important for exenatide's effect to reduce weight.…”

Section: Glp-1 Receptor Agonistscontrasting

confidence: 52%

Impact of Newer Medications for Type 2 Diabetes on Body Weight

Pedersen¹

2013

Curr Obes Rep

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Most patients with type 2 diabetes (T2DM) struggle with excess body weight. Many management strategies for achievement of euglycemia in T2DM are associated with weight gain, which worsens insulin resistance over time, increases health risk associated with obesity, and is associated with poor compliance with treatment. This review will discuss a host of new medications for management of hyperglycemia that have emerged and are emerging which are weight neutral, or facilitate weight loss. Incretin therapies are reviewed, including DPP-4 inhibitors which are weight neutral, and GLP-1 receptor agonists which can facilitate weight loss. SGLT-2 inhibitors, anticipated to become available soon, facilitate modest weight loss. Pramlintide can improve glycemic control and facilitate weight loss in T2DM patients on concomitant insulin therapy. The bile acid sequestering agent colesevelam, more recently approved for management of T2DM, modestly improves glycemic control and is weight neutral. The advent of these newer therapies makes it increasingly possible to optimize concomitant management of type 2 diabetes and obesity.

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Section: Glp-1 Receptor Agonistscontrasting

confidence: 52%

Impact of Newer Medications for Type 2 Diabetes on Body Weight

Pedersen¹

2013

Curr Obes Rep

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“…Moreover, nausea scores did not differ between treatments. In addition, although it has been shown that liraglutide exerts a short-term reduction in gastric emptying, this effect is markedly diminished after short-term repeated dosing of liraglutide, whereas the body weight loss continues (34). Results from other studies with GLP-1RA treatment also provide arguments against nausea or delayed gastric emptying as explanations for the appetite-and body weightreducing effects of GLP-1RA treatment.…”

Section: Resultsmentioning

confidence: 66%

Liraglutide Reduces CNS Activation in Response to Visual Food Cues Only After Short-term Treatment in Patients With Type 2 Diabetes

et al. 2015

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OBJECTIVEGlucagon-like peptide-1 receptor agonists (GLP-1RAs) are associated with reduced appetite and body weight. We investigated whether these effects could be mediated by the central nervous system (CNS). RESEARCH DESIGN AND METHODSWe performed a randomized crossover study in obese patients with type 2 diabetes (n = 20, mean age 59.3 6 4.1 years, mean BMI 32 6 4.7 kg/m 2 ), consisting of two periods of 12-week treatment with either liraglutide 1.8 mg or insulin glargine. Using functional MRI, we determined the effects of treatment on CNS responses to viewing food pictures in the fasted condition and 30 min after meal intake. RESULTSAfter 12 weeks, the decrease in HbA 1c was larger with liraglutide versus insulin glargine (D20.7% vs. 20.2%, P < 0.001). Body weight decreased during liraglutide versus insulin glargine (D23.3 kg vs. 0.8 kg, P < 0.001). After 10 days, patients treated with liraglutide, compared with insulin glargine, showed decreased responses to food pictures in insula and putamen (P £ 0.02). In addition, liraglutide enhanced the satiating effect of meal intake on responses in putamen and amygdala (P £ 0.05). Differences between liraglutide and insulin glargine were not observed after 12 weeks. CONCLUSIONSCompared with insulin, liraglutide decreased CNS activation significantly only after short-term treatment, suggesting that these effects of GLP-1RA on the CNS may contribute to the induction of weight loss, but not necessarily to its maintenance, in view of the absence of an effect of liraglutide on CNS activation in response to food pictures after longer-term treatment.Obesity and diabetes constitute a major health burden due to their pandemic occurrence (1) and their association with adverse consequences, such as cardiovascular disease (2). Obesity is the result of a long-term excess energy intake relative to expenditure, leading to increased weight and body fat mass. The central nervous system (CNS) has a major role in the regulation of food intake and the maintenance

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“…GE in healthy individuals exhibits a wide interindividual variation of~4-17 kJ/min (~1-4 kcal/min) [14]; this is increased in diabetes because of the high prevalence of delayed [15], and occasionally rapid, GE [16]. The reduction in postprandial glucose following acute administration of GLP-1 [17][18][19] or 'short-acting' GLP-1 agonists [20,21] relates primarily to slowing of GE but clinical studies relating to the effects of GLP-1 and its agonists on BP have not discriminated between effects on fasting vs postprandial BP.…”

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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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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Liraglutide: short‐lived effect on gastric emptying—long lasting effects on body weight

Cited by 154 publications

References 48 publications

Impact of Newer Medications for Type 2 Diabetes on Body Weight

Impact of Newer Medications for Type 2 Diabetes on Body Weight

Liraglutide Reduces CNS Activation in Response to Visual Food Cues Only After Short-term Treatment in Patients With 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

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