scholarly journals No Acute Effects of Exogenous Glucose-Dependent Insulinotropic Polypeptide on Energy Intake, Appetite, or Energy Expenditure When Added to Treatment With a Long-Acting Glucagon-Like Peptide 1 Receptor Agonist in Men With Type 2 Diabetes

Diabetes Care ◽  
2020 ◽  
Vol 43 (3) ◽  
pp. 588-596 ◽  
Author(s):  
Natasha C. Bergmann ◽  
Lærke S. Gasbjerg ◽  
Sebastian M. Heimbürger ◽  
Liva S.L. Krogh ◽  
Flemming Dela ◽  
...  
2018 ◽  
Vol 315 (4) ◽  
pp. R595-R608 ◽  
Author(s):  
Jacob D. Brown ◽  
Danielle McAnally ◽  
Jennifer E. Ayala ◽  
Melissa A. Burmeister ◽  
Camilo Morfa ◽  
...  

Long-acting glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) agonists (GLP-1RA), such as exendin-4 (Ex4), promote weight loss. On the basis of a newly discovered interaction between GLP-1 and oleoylethanolamide (OEA), we tested whether OEA enhances GLP-1RA-mediated anorectic signaling and weight loss. We analyzed the effect of GLP-1+OEA and Ex4+OEA on canonical GLP-1R signaling and other proteins/pathways that contribute to the hypophagic action of GLP-1RA (AMPK, Akt, mTOR, and glycolysis). We demonstrate that OEA enhances canonical GLP-1R signaling when combined with GLP-1 but not with Ex4. GLP-1 and Ex4 promote phosphorylation of mTOR pathway components, but OEA does not enhance this effect. OEA synergistically enhanced GLP-1- and Ex4-stimulated glycolysis but did not augment the hypophagic action of GLP-1 or Ex4 in lean or diet-induced obese (DIO) mice. However, the combination of Ex4+OEA promoted greater weight loss in DIO mice than Ex4 or OEA alone during a 7-day treatment. This was due in part to transient hypophagia and increased energy expenditure, phenotypes also observed in Ex4-treated DIO mice. Thus, OEA augments specific GLP-1RA-stimulated signaling but appears to work in parallel with Ex4 to promote weight loss in DIO mice. Elucidating cooperative mechanisms underlying Ex4+OEA-mediated weight loss could, therefore, be leveraged toward more effective obesity therapies.


2012 ◽  
Vol 58 (3) ◽  
pp. 51-55
Author(s):  
E N Ostroukhova ◽  
O K Khmel'nitskiĭ ◽  
E I Krasil'nikova ◽  
K S Davidenko

This paper reports the results of the treatment of 71 patients presenting with type 2 diabetes mellitus using liraglutide, a long-acting analog of glucagon-like peptide-1 (GLP-1) marketed under the brand name Victoza. Practically all the patients experienced either improvement or normalization of the parameters of carbohydrate metabolism in conjunction with a reduction of their body weight and arterial pressure. There were no severe hypoglycemic episodes and other adverse reactions to the therapy. It is recommended that Victoza should be more widely used for the treatment of the patients with type 2 diabetes mellitus.


2021 ◽  
Author(s):  
Ashref Kayed ◽  
Simone Melander ◽  
Kim Andreassen ◽  
Morten Karsdal ◽  
Kim Henriksen

Abstract Obesity-related metabolic disorders, including non-alcoholic fatty liver disease and its more progressive form non-alcoholic steatohepatitis, are causing an increased health burden, especially due to the lack of approved treatment options. Using preclinical models of NASH, obesity, and type 2 diabetes, we investigated the effects of a long-acting glucagon-like peptide-1(GLP-1) and glucagon (GCG) receptor agonist OXM-104 head to head with once-daily GLP-1/GCG receptor agonist cotadutide and once-weekly GLP-1 receptor agonist semaglutide. OXM-104, cotadutide, and semaglutide elicited marked reductions in body weight and improved glucose control. In contrast, hepatoprotective effects, i.e., reductions in steatosis and fibrosis, as well as liver fibrosis biomarkers, were more prominent with OXM-104 and cotadutide than effects seen with semaglutide. This is demonstrated by improved NAFLD activity score (NAS) by OXM-104 and cotadutide which underlines the importance of the GCG receptor. Thus, these results underline the potential of OXM-104 as a promising therapeutic option for the resolution of NASH, but also as a therapeutic option for type 2 diabetes and obesity.


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