Is it Time to Expand Glucagon-like Peptide-1 Receptor Agonist Use for Weight Loss in Patients Without Diabetes?

Drugs ◽  
2021 ◽  
Author(s):  
Wendy H. Updike ◽  
Olivia Pane ◽  
Rachel Franks ◽  
Faizah Saber ◽  
Farah Abdeen ◽  
...  
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.


2010 ◽  
Vol 8 (1) ◽  
pp. 12 ◽  
Author(s):  
Celeste C L Quianzon ◽  
Mansur E Shomali ◽  
◽  

The glucagon-like peptide-1 receptor agonist diabetes medications have become important due to their unique features, such as their potency of glycosylated haemoglobin (HbA1C) lowering, durability of effect, glucose-depending insulin secretion resulting in a low risk of hypoglycaemia, glucagon suppression and weight loss. Lixisenatide is an investigational compound in this class, exhibits all of these features, and has some unique properties, which are highlighted in this review. The pharmacology of lixisenatide, the results of recent clinical trials investigating this agent, and its potential role in the management of type 2 diabetes will be discussed.


2011 ◽  
Vol 07 (02) ◽  
pp. 104
Author(s):  
Celeste C L Quianzon ◽  
Mansur E Shomali ◽  
◽  

The glucagon-like peptide-1 receptor agonist diabetes medications have become important due to their unique features, such as their potency of glycosylated hemoglobin (HbA1C) lowering, durability of effect, glucose-depending insulin secretion resulting in a low risk of hypoglycemia, glucagon suppression, and weight loss. Lixisenatide is an investigational compound in this class, exhibits all of these features, and has some unique properties, which are highlighted in this review. The pharmacology of lixisenatide, the results of recent clinical trials investigating this agent, and its potential role in the management of type 2 diabetes will be discussed.


2020 ◽  
Vol 26 (2) ◽  
pp. 235-240 ◽  
Author(s):  
Carla Maccora ◽  
Cristina Ciuoli ◽  
Arianna Goracci ◽  
Nicoletta Benenati ◽  
Caterina Formichi ◽  
...  

Objective: Liraglutide is a glucagon-like peptide 1 receptor agonist which acts through peripheral and central receptor pathways affecting food intake. Preliminary identification of responder patients represents a crucial point to reduce an inappropriate exposure to the drug and the health expenditure. The primary endpoint of our study was to identify predictors of liraglutide efficacy in the short term follow-up. The secondary endpoint was to evaluate the treatment efficacy stratified by the underlying psychiatric disorder. Methods: We evaluated a cohort of 100 patients (77 females, 23 males, mean body mass index 38.6 ± 3.2 kg/m2) who were evaluated at baseline, and after 1, 3, and 6 months of treatment. Liraglutide efficacy was defined by a weight loss ≥5% of initial weight. Sociodemographic/metabolic parameters, food intake, smoking habit, and physical activity were correlated with liraglutide efficacy. Results: There was a significant weight loss after 1 month of therapy, as well as after 3 and 6 months when compared to the baseline ( P<.0001; 27%, 45%, and 57% of patients showed a weight loss ≥5%, respectively). No difference was found in weight loss between the 3 groups of patients (with binge eating, with/without psychiatric disorders). The weight loss at 1 month was the only predictor of a positive response to the treatment. Conclusion: Our results confirm the efficacy of liraglutide even at a lower dose than conventional. The early response to the drug seems to be a good predictor of long-term efficacy and it might be useful in clinical practice to identify patients in whom liraglutide may induce a significant weight loss. Abbreviations: BMI = body mass index; EMA = European Medicine Agency; FDA = Food and Drug Administration; GLP-1 RA = glucagon-like peptide 1 receptor agonist


2019 ◽  
Vol 25 (9) ◽  
pp. 935-942 ◽  
Author(s):  
Janelle B. Gyorffy ◽  
Andrea N. Keithler ◽  
Jana L. Wardian ◽  
Lee A. Zarzabal ◽  
Alexander Rittel ◽  
...  

Objective: The clinical benefit of adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to basal-bolus or very high dose insulin regimens is unclear. This study investigated the impact of adding a GLP-1RA to a spectrum of insulin regimens (basal, basal-bolus, and U-500) to determine the impact on hemoglobin A1c (HbA1c), weight loss, and total daily insulin dose (TDD) over the course of 12 months. Methods: A retrospective chart review was conducted on 113 participants with type 2 diabetes mellitus using insulin therapy. Each participant's HbA1c, body weight, and TDD were recorded prior to initiation of GLP-1RA therapy and at the 3, 6, and 12-month time points while on combination therapy. Results: Across all participants, the HbA1c values decreased significantly from a baseline of 8.9 (74 mmol/mol) ± 0.14% to 8.2 (66 mmol/mol) ± 0.14% ( P<.01) in the first 3 months, 8.0 (64 mmol/mol) ± 0.12% ( P<.01) at 6 months, to 8.3 (67 mmol/mol) ± 0.14% ( P<.01) at 12 months. There was no significant decrease in weight or TDD with the addition of a GLP-1RA overall or in different insulin groups. However, there was a clinically significant decrease in weight over the study duration. Conclusion: The results of this study suggest that adding a GLP-1RA to various insulin regimens may help to achieve glycemic goals while avoiding the less desirable side effects of weight gain and increasing insulin regimens. However, the expected weight loss and decrease in TDD may not be as sizable in the clinical setting. Abbreviations: DCOE = Diabetes Center of Excellence; DM = diabetes mellitus; GLP-1RA = glucagon-like peptide-1 receptor agonist; HbA1c = hemoglobin A1c; RCT = randomized controlled trial; TDD = total daily dose


2015 ◽  
Vol 6 (1) ◽  
pp. 73-78 ◽  
Author(s):  
B. M. Nathan ◽  
K. D. Rudser ◽  
M. J. Abuzzahab ◽  
C. K. Fox ◽  
B. J. Coombes ◽  
...  

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