Effects of GLP-1 on appetite and weight

Shah, Meera; Vella, Adrian

doi:10.1007/s11154-014-9289-5

Cited by 229 publications

(183 citation statements)

References 73 publications

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“…An effect on UGE superior to that of selective SGLT2 inhibition in preclinical studies was observed (unpublished results); however, this has not been tested in the clinical setting. 32 A recent study showed that glucagon increases energy expenditure and decreases adipose tissue expansion in humans. value of up to 70% inhibition of renal glucose reabsorption, which is higher than that previously reported with SGLT2 inhibitors.…”

Section: Discussionmentioning

confidence: 99%

The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes

He¹,

Haynes

Meyers³

et al. 2019

Diabetes Obesity Metabolism

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BACKGROUND: There is an unmet need for a safer and more effective treatment for obesity.This study assessed the effects of licogliflozin, a dual inhibitor of sodium-glucose co-transporter (SGLT) 1/2, on body weight, metabolic parameters and incretin hormones in patients with type 2 diabetes mellitus (T2DM) and/or obesity. METHODS:Patients with obesity (BMI, 35-50 kg/m 2 ) were enrolled into a 12-week study (N = 88; licogliflozin 150 mg q.d.). Patients with T2DM were enrolled into a second, two-part study, comprising a single-dose cross-over study (N = 12; 2.5 − 300 mg) and a 14-day dosing study (N = 30; 15 mg q.d). Primary endpoints included effects on body weight, effects on glucose, safety and tolerability. Secondary endpoints included urinary glucose excretion (UGE 24 ) and pharmacokinetics, while exploratory endpoints assessed the effects on incretin hormones (total GLP-1, PYY 3-36 , and GIP), insulin and glucagon.RESULTS: Treatment with licogliflozin 150 mg q.d. for 12 weeks in patients with obesity significantly reduced body weight by 5.7% vs placebo (P < 0.001) and improved metabolic parameters such as significantly reduced postprandial glucose excursion (21%; P < 0.001), reduced insulin levels (80%; P < 0.001) and increased glucagon (59%; P < 0.001). In patients with T2DM, a single dose of licogliflozin 300 mg in the morning prior to an oral glucose tolerance test (OGTT) remarkably reduced glucose excursion by 93% (P < 0.001; incremental AUC 0-4h ) and suppressed insulin by 90% (P < 0.01; incremental AUC 0-4h ). Treatment with licogliflozin 15 mg q.d. for 14 days reduced 24-hour average glucose levels by 26% (41 mg/dL; P < 0.001) and increased UGE 24 to 100 g (P < 0.001) in patients with T2DM. In addition, this treatment regimen significantly increased total GLP-1 by 54% (P < 0.001) and PYY 3-36 by 67% (P < 0.05) post OGTT vs placebo, while significantly reducing GIP levels by 53% (P < 0.001). Treatment with licogliflozin was generally safe and well tolerated. Diarrhea (increased numbers of loose stool) was the most common adverse event in all studies (90% with licogliflozin vs 25% with placebo in the 12-week study), while a lower incidence of flatulence, abdominal pain and abdominal distension (25%-43% with licogliflozin vs 9%-11% with placebo in the 12-week study) were among the other gastrointestinal events reported. CONCLUSION: Licogliflozin treatment (1-84 days) leads to significant weight loss and favourable changes in a variety of metabolic parameters and incretin hormones. Dual inhibition of SGLT1/2 with licogliflozin in the gut and kidneys is an attractive strategy for treating obesity and diabetes. K E Y W O R D S clinical trial, continuous glucose monitoring (CGM), incretins, obesity therapy, phase I-II study, weight control

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Section: Discussionmentioning

confidence: 99%

The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes

He¹,

Haynes

Meyers³

et al. 2019

Diabetes Obesity Metabolism

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“…Thus, high leptin and low ghrelin suppress the appetite, while low GLP-1 and glucagon contribute to appetite stimulation. The final effect on a child will also depend on meal content, the amount of high-fat and sugar, including fructose, the amount and distribution of body and liver fat content, the effects on insulin sensitivity and glucose metabolism, the basal nutritional status, gonadal status, exercise level, the integrity of the brain-gut axis, and their genetic susceptibility for diabetes mellitus (Bouret, 2013;Pettus et al, 2013;Korek et al, 2013;Shah and Vella, 2014;Liu et al, 2014aLiu et al, , 2014bLiu et al, , 2014cLaughlin,2014). Low levels of ghrelin are of concern in children given its involvement in the regulation of growth hormone, memory and learning, food addiction and neuroprotection (Albarran-Zeckler et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease

Calderón‐Garcidueñas

Franco-Lira

D’Angiulli

et al. 2015

Environmental Research

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“…In mice, GLP-1 excretion is circadian, with larger amounts being released in the evening, and is highly entrained by feeding behavior [82]. GLP-1 affects satiety in the central nervous system [83] and can influence metabolic homeostasis by affecting hepatic gene expression. GLP-1 receptor activation in hepatocytes increases cAMP production as well as peroxisome proliferator-activated receptor α (PPARα) and acetyl-CoA oxidase expression, both of which are involved in fatty acid oxidation.…”

Section: Gut Signaling and Feeding Entrainmentmentioning

confidence: 99%

Daily Eating Patterns and Their Impact on Health and Disease

Zarrinpar

Chaix

Panda

2016

Trends in Endocrinology & Metabolism

226

228

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Cyclical expression of cell-autonomous circadian clock components and key metabolic regulators coordinate often discordant and distant cellular processes for efficient metabolism. Perturbation of these cycles, either by genetic manipulation, disruption of light/dark cycles, or, most relevant to the human population, via eating patterns, contributes to obesity and dysmetabolism. Time-restricted feeding (TRF), during which time of access to food is restricted to a few hours, without caloric restriction, supports robust metabolic cycles and protects against nutritional challenges that predispose to obesity and dysmetabolism. The mechanism by which TRF imparts its benefits is not fully understood but likely involves entrainment of metabolically active organs through gut signaling. Understanding the relationship of feeding pattern and metabolism could yield novel therapies for the obesity pandemic.

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Effects of GLP-1 on appetite and weight

Cited by 229 publications

References 73 publications

The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes

The effects of licogliflozin, a dual SGLT1/2 inhibitor, on body weight in obese patients with or without diabetes

Mexico City normal weight children exposed to high concentrations of ambient PM2.5 show high blood leptin and endothelin-1, vitamin D deficiency, and food reward hormone dysregulation versus low pollution controls. Relevance for obesity and Alzheimer disease

Daily Eating Patterns and Their Impact on Health and Disease

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