Liraglutide for psychiatric disorders: clinical evidence and challenges

Author(s):  
Mehmet Akif Camkurt ◽  
Luca Lavagnino ◽  
Xiang Y. Zhang ◽  
Antonio L Teixeira

Abstract Obesity and diabetes are both risk factors and consequences of psychiatric disorders. Glucagon like peptide 1 (GLP-1) receptor agonists such as liraglutide are widely used in the treatment of diabetes and obesity. There are considerable amounts of preclinical studies showing the effects of liraglutide on promotion of neurogenesis, while preventing apoptosis and oxidation. Preliminary clinical evidence has suggested that liraglutide could decrease weight gain, improve cognition and prevent cognitive decline. Accordingly, liraglutide has been regarded as a potential candidate for the management of psychiatric disorders. Herein, we will discuss the association between obesity/diabetes and psychiatric disorders, and the emerging use of liraglutide in psychiatry.

2016 ◽  
Vol 474 (1) ◽  
pp. 47-50 ◽  
Author(s):  
Emma K. Biggs ◽  
Fiona M. Gribble ◽  
Frank Reimann

Treatments for diabetes and obesity based on enteroendocrine hormones are a focus of research interest, partly due to the successes of glucagon-like peptide-1 (GLP-1) mimetic peptides in the treatment of diabetes and the correlation of altered enteroendocrine profiles with the positive metabolic outcomes of gastric bypass surgery. It is thought that simultaneous stimulation of more than one receptor might mimic the superior efficacy of the latter and dual or triple-agonist peptides are under investigation. An important step in developing multiple agonists is to establish the relative pharmacological potency and efficacy of new molecules at its different target receptors, and to optimise the balance of activities to achieve the desired treatment outcome. In a recent issue of the Biochemical Journal, Naylor et al. described how they used CRISPR technology to modulate endogenous receptor density in insulinoma cells to get the balance right for a dual incretin peptide engaging both GLP-1- and glucose-dependent insulinotropic polypeptide-receptors.


2021 ◽  
Vol 36 (3) ◽  
pp. 251-259
Author(s):  
Yi Tian ◽  
Peiyu Liu ◽  
Weisong Liu ◽  
Qiaojing Xu ◽  
Xiangkun Zhao

General anesthesia is necessary for patients to undergo surgery and invasive procedures. However, numerous preclinical studies have demonstrated widespread developmental neurotoxicity of the commonly used anesthetics and sedatives for the immature brain. Clinical studies also suggest a strong correlation between childhood anesthesia exposure and subsequent behavioral or cognitive impairment in adulthood. These findings have attracted increasing attention of anesthesiologists, pediatricians, and caregivers about the safety of anesthesia exposure in children, especially during early childhood. Herein, the aim of this review was to present the molecular mechanism of general anesthesia and its effects on the developing brain and introduce the recent clinical evidence of changes in cognition function post-childhood general anesthesia exposure. More importantly, some of the spots will be importantly discussed to scrutinize the phenomena; only in this way, it may help minimize or eliminate relevant risk factors.


2015 ◽  
Vol 11 (11) ◽  
pp. 3188-3193 ◽  
Author(s):  
Simone Queiroz Pantaleão ◽  
Vinicius Gonçalves Maltarollo ◽  
Sheila Cruz Araujo ◽  
Jadson Castro Gertrudes ◽  
Kathia Maria Honorio

DPP-4 is an important biological target related to the treatment of diabetes since some inhibitors can lead to an increase in the insulin levels and the prolonged activity of glucagon-like peptide-1 and gastric inhibitory polypeptide, being effective in glycemic control.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Alina Yu. Babenko ◽  
Daria A. Savitskaya ◽  
Yulia A. Kononova ◽  
Aleksandra Yu. Trofimova ◽  
Anna V. Simanenkova ◽  
...  

Rationale. It is well known that diabetes mellitus (DM) exacerbates the mechanisms underlying atherosclerosis. Currently, glucagon-like peptide-1 receptor agonists (aGLP-1) have one of the most prominent cardioprotective effects among the antidiabetic agents. However, the treatment with aGLP-1 is effective only in 50-70% of the cases. Taking into account the high cost of these medications, discovery of the predictors of optimal response to treatment is required. Purpose. To identify the predictors of the greater impact of aGLP-1 on HbA1c levels, weight reduction, and improvement in lipid profile. Methods. The study group consisted of 40 patients with type 2 DM (T2DM) and obesity who were treated with aGLP-1. The follow-up period was 24 weeks. Patients’ evaluation was conducted at baseline and after 24 weeks. In addition, it included the assessment of the hormones involved in glucose and lipid metabolism and appetite regulation. Results. Patients who have initially higher BMI (body mass index), glycemia, and triglycerides (TG) had better improvement in these parameters undergoing aGLP-1 treatment. In patients with a BMI loss≥5%, GLP-1 and fasting ghrelin levels were higher and ghrelin level in postnutritional status was lower. The HbA1c levels decreased more intensively in participants with higher GLP-1 levels. TG responders had lower baseline fasting glucose-dependent insulinotropic peptide (GIP) and postprandial ghrelin levels. Conclusion. The evaluation of the glycemic control, lipid profile, and GLP-1, GIP, and ghrelin levels are useable for estimating the expected efficacy of aGLP-1.


2008 ◽  
Vol 61 (4) ◽  
pp. 401-409 ◽  
Author(s):  
L R Ranganath

Incretins such as glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are intestinal postprandial hormones that stimulate insulin release from the pancreas as long as circulating glucose concentrations are raised. In addition to their effect on insulin secretion and consequent glucose lowering, GIP and GLP-1, especially the latter, have a number of physiological effects such as inhibition of glucagon release, gastric emptying and food intake, as well as a tropic action on pancreatic B-cell mass. There is currently a pandemic of obesity and diabetes, and existing treatments are largely inadequate both in regard to efficacy as well as their ability to tackle important factors in the pathogenesis of type 2 diabetes (T2D). There is increasing evidence that current treatments do not address the issue of progressive B-cell failure in T2D. Since obesity is the engine that is driving the epidemic of diabetes, it is disappointing that most treatments that succeed in lowering plasma glucose are also associated with weight gain. It is now well established that intensively treated T2D has a better outcome than standard treatment. Consequently, achieving better control of diabetes with lower HbA1c is the goal of optimal treatment. Despite the use of usual therapeutic agents in T2D, often in high doses and as combinations, such as metformin, sulphonylurea, α-glycosidase inhibitors, thiazolidinediones and a number of animal and human insulin preparations, optimal control of glycaemia is not achieved. The use of incretins as therapeutic agents offers a new approach to the treatment of T2D.


2018 ◽  
Vol 13 (1) ◽  
pp. 41-48 ◽  
Author(s):  
Guojun Chen ◽  
Jicheng Yu ◽  
Zhen Gu

Antidiabetic therapeutics, including insulin as well as glucagon-like peptide 1 (GLP-1) and its analogs, are essential for people with diabetes to regulate their blood glucose levels. Nevertheless, conventional treatments based on hypodermic administration is commonly associated with poor blood glucose control, a lack of patient compliance, and a high risk of hypoglycemia. Closed-loop drug delivery strategies, also known as self-regulated administration, which can intelligently govern the drug release kinetics in response to the fluctuation in blood glucose levels, show tremendous promise in diabetes therapy. In the meantime, the advances in the development and use of microneedle (MN)-array patches for transdermal drug delivery offer an alternative method to conventional hypodermic administration. Hence, glucose-responsive MN-array patches for the treatment of diabetes have attracted increasing attentions in recent years. This review summarizes recent advances in glucose-responsive MN-array patch systems. Their opportunities and challenges for clinical translation are also discussed.


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