Search

BACKGROUND: Obesity is an independent risk factor for complications after abdominal hernia repair. Glucagon-like-peptide-1 (GLP-1) receptor agonists are gaining popularity as pharmacologic weight loss adjuncts and may help patients reach weight loss goals for surgery. We examine our early experience utilizing GLP-1 agonists versus lifestyle modifications alone to achieve weight loss in patients before elective hernia repair. METHODS: This single-center, retrospective review identified obese patients who underwent elective hernia repair from 2014 to 2023. Patients were asked to achieve a BMI ≤ 33 kg/m2 before surgery. Patients who lost weight with GLP-1 therapy in addition to lifestyle changes were compared to a control cohort that achieved similar preoperative weight loss without GLP-1 therapy. Primary outcome was mean time from GLP-1 agonist initiation and initial surgery clinic visit to surgery. Secondary outcomes were 30-day morbidity, mortality, and reoperation rates, and hernia recurrence. RESULTS: Forty-six patients with ventral/incisional, flank, umbilical, parastomal, inguinal, and hiatal hernias were identified (GLP-1 N = 24, control N = 22). 81.8% (N = 18) of controls had a ventral/incisional hernia, compared to 45.8% (N = 11) of GLP-1 patients (p = 0.03). Mean BMI at GLP-1 agonist initiation was similar to mean BMI at initial clinic visit for controls (38.1 ± 4.9 vs 38.2 ± 2.7 kg/m2, p = 0.66). Preoperative mean percentage total weight loss (14.9 ± 7.5 vs 12.4 ± 6.9 kg, p = 0.39) and mean BMI reduction (6.0 ± 3.8 vs 4.9 ± 2.3 kg/m2, p = 0.43) were similar between groups. The mean time from GLP-1 agonist initiation to surgery was significantly shorter than initial clinic visit to surgery for controls (6.3 ± 4.0 vs 14.7 ± 17.6 months, p = 0.03). There was no statistically significant difference in time from initial clinic visit to surgery between groups (7.6 ± 4.4 vs 14.7 ± 17.6 months, p = 0.06). There was no significant difference in 30-day morbidity between groups (8.3 vs 27.3%, p = 0.13). CONCLUSION: GLP-1 agonists accelerate preoperative weight loss for obese hernia patients without negatively impacting postoperative outcomes.

Reports of suicidality associated with glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been reported to the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA). We previously reported an increased reporting odds ratio (ROR) of some measures of suicidality with semaglutide and liraglutide using the FDA Adverse Event Reporting System (FAERS). Notwithstanding the increased ROR, causality between GLP-1 RAs exposure and any aspect of suicidality is not established. The analysis herein aims to extend a previous analysis of the FAERS by evaluating the ROR for suicidality reported to the World Health Organization (WHO) Pharmacovigilance Database (VigiBase). We aimed to characterize the ROR of suicidality associated with GLP-1 RAs, as extrapolated from spontaneous reports. As per our previous report, the ROR was considered significant when the lower limit of the 95 % confidence (CI) was >1.0. We searched VigiBase reports from inception to January 2024. The RORs for suicidal ideation were significantly increased for semaglutide (5.82), liraglutide (4.03) and tirzepatide (2.25). For "depression/suicidal", the ROR was significantly increased for semaglutide (14.74) and liraglutide (5.86); and for suicidal behaviour, the ROR was significantly increased for semaglutide (6.52) and liraglutide (3.90). However, for suicide attempts, the ROR was significantly decreased for semaglutide (0.11), dulaglutide (0.075), exenatide (0.047) and liraglutide (0.15). For completed suicide, the ROR was also significantly decreased for semaglutide (0.01), dulaglutide (0.003), exenatide (0.002) and liraglutide (0.008). Unlike our previous report with FAERS, a mixed pattern of ROR emerged in the WHO VigiBase with respect to suicidality and exposure to select GLP-RAs. Causation between GLP-1 RA exposure and suicidality (either increased or decreased) cannot be ascertained from ROR data. • A mixed pattern of ROR emerged with respect to suicidality and select GLP-1 RAs • RORs for suicide ideation increased for semaglutide, liraglutide, and tirzepatide • RORs for suicide attempts decreased for semaglutide, dulaglutide, and liraglutide • RORs for suicide completion decreased for semaglutide, dulaglutide, and liraglutide [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study is to explore the rational pricing range for the once‐weekly administration of insulin icodec in the treatment of type 2 diabetes patients in China who have already received basal insulin therapy. Methods: The data foundation of this study originates from the ONWARDS 4 clinical trial and research materials on Chinese type 2 diabetes patients. By comprehensively applying cost‐utility analysis methods and binary search techniques, the appropriate price positioning of insulin icodec was determined from the perspective of China's healthcare system. Results: In the long‐term treatment simulation, we found that insulin icodec and insulin glargine performed similarly in terms of quality‐adjusted life years (QALYs), with 10.15 and 10.07 years, respectively. Although the annual cost of insulin icodec was initially assumed to be equivalent to that of insulin glargine, in‐depth analysis revealed that insulin icodec may have higher cost‐effectiveness potential. Further price sensitivity analysis indicated that the reasonable cost range of insulin icodec lies between $851.95 and $1358.25. After fine‐tuning through univariate sensitivity analysis, this cost range was revised to $784.90 to $1145.96, a conclusion that was robustly validated in subsequent probabilistic sensitivity analysis and scenario simulations. Conclusion: The conclusion drawn from this study is that, with insulin glargine as the cost reference, the economic cost of insulin icodec for Chinese type 2 diabetes patients is expected to range from $784.90 to $1145.96, providing a reference basis for clinical decision‐making and healthcare policy formulation. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a potent therapeutic option for the management of obesity, demonstrating exceptional efficacy in several large-scale clinical trials. Despite their promising therapeutic outcomes, the rising popularity of these agents raises significant concerns, particularly regarding their off-label use by individuals seeking weight loss for aesthetic reasons rather than addressing underlying metabolic health conditions. This article critically evaluates the efficacy and safety of GLP-1 RAs in obesity management. Additionally, it explores the economic implications and ethical challenges associated with the increasing demand for GLP-1 RAs. By addressing these dimensions, this article aims to facilitate informed and responsible decision-making in clinical practice, highlighting the need for individualized patient assessments and careful consideration of both short- and long-term safety risks. [ABSTRACT FROM AUTHOR]

Clozapine has been considered the "gold standard" in the treatment of schizophrenia for many years. Clozapine has a superior effect, particularly in the treatment of negative symptoms and suicidal behaviour. However, due to its numerous adverse reactions, clozapine is mainly used for treatment-resistant schizophrenia. The aim of this paper is to analyze the results of clinical studies on clozapine from 2012-2022. PubMed was used as the database. Sixty-four studies were included and categorised by topic. The pharmacokinetic properties of clozapine tablets and a clozapine suspension solution did not differ markedly. Clozapine was superior to olanzapine and risperidone in reducing aggression and depression. A long-term study showed that metabolic parameters changed comparably with olanzapine and clozapine after 8 years. Risperidone and ziprasidone can be used as an alternative to clozapine. Scopolamine, atropine drops, and metoclopramide are effective in the treatment of clozapine-induced hypersalivation. Eight drugs, including liraglutide, exenatide, metformin, and orlistat, are potentially effective in the treatment of clozapine-induced weight gain. Ziprasidone, haloperidol, and aripiprazole showed a positive effect on symptoms when added to clozapine. No investigated drug was superior to clozapine for the treatment of schizophrenia. Ziprasidone and risperidone can also be used well for the treatment of schizophrenia. In the treatment of clozapine-induced hypersalivation and weight gain, some drugs proved to be effective. [ABSTRACT FROM AUTHOR]

Background: Nicotine use and nicotine use disorder (NUD) are the leading causes of preventable death in the United States. Persons with mental disorders (e.g., bipolar disorder) are differentially susceptible to nicotine use. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are indicated for type 2 diabetes mellitus (T2DM) and obesity and show preliminary evidence of efficacy in addiction-related behaviours. Herein, we synthesize extant preclinical and clinical evidence evaluating the effect of GLP-1RAs on neurobiological systems and behaviours salient to nicotine consumption and cessation. Methods: Online databases (MedLine, Embase, AMED, PsychINFO, JBI EBP Database, PubMed, Web of Science, Google Scholar) were searched from inception to May 21, 2024. Relevant studies were also extracted from the reference lists of the obtained articles. All articles were screened against inclusion and exclusion criteria. Results: Administration of GLP-1RAs reduced nicotine self-administration and nicotine-seeking behaviour in animal models that, in some cases, is sustained beyond exposure to the agent. GLP-1RAs also mitigated post-nicotine cessation weight gain, craving, withdrawal, and hyperphagia. The preceding effects are attributable to modulation of reward-related brain regions (e.g., mesolimbic dopamine system), resulting in nicotine aversion. GLP-1RAs were also efficacious as adjunctive therapies [e.g., in combination with nicotine replacement therapies (NRTs)]. Conclusion: The multi-effect characteristics in NUD paradigms provide a compelling rationale for large, adequately powered, long-term, randomized controlled trials of GLP-1RAs in the treatment and prevention of NUD. The replicated effect on mitigating post-nicotine cessation weight gain is a differentiating feature of GLP-1RAs from extant proven therapies for NUD. [ABSTRACT FROM AUTHOR]

This article examines the early adoption of semaglutide, a drug used to treat type 2 diabetes, in Scandinavia, with a focus on Denmark. The study analyzes nationwide prescription data from Denmark, Norway, and Sweden to compare the use of semaglutide with other glucose-lowering drugs and to compare the characteristics of semaglutide initiators with initiators of other drugs. The findings reveal that semaglutide is widely used in Scandinavia and that the characteristics of semaglutide initiators differ slightly from initiators of other drugs. The study also identifies differences between early and late initiators of semaglutide, suggesting potential off-label use for weight loss. However, the study acknowledges limitations, such as the lack of data on specific indications for use. [Extracted from the article]

The meta-analysis examined the association between GLP-1 receptor agonists and the risk of ischemic optic neuropathy in patients with obesity and/or type 2 diabetes. While some observational studies suggested a potential link, the meta-analysis of randomized controlled trials did not find a significant detrimental effect of GLP-1 RA therapy on optic neuropathy. The estimated incidence of optic ischemic neuropathy was higher in the GLP-1 RA arm compared to the placebo arm, but the difference was not statistically significant. Further research is needed to fully understand the safety profile of GLP-1 RA, especially in patients at higher risk for optic neuropathy. [Extracted from the article]

The article discusses a post hoc analysis of a phase 2 clinical trial on survodutide, a dual agonist for glucagon and GLP-1 receptors, in adults with obesity. The study showed significant weight loss and reductions in blood pressure with survodutide treatment compared to placebo. The results suggest that survodutide may help alleviate cardiovascular risk, regardless of hypertension status at baseline. The study was supported by Boehringer Ingelheim, and the authors disclosed potential conflicts of interest related to the research. [Extracted from the article]

Previous researches found that glucagon‐like peptide 1 receptor agonists (GLP‐1RA) offer benefits beyond their anti‐diabetic properties, including weight loss and cardiovascular disease prevention. However, the effects of GLP‐1RA on diabetic peripheral neuropathy (DPN) remain unclear. This meta‐analysis aims to assess the potential benefits of GLP‐1RA treatment in DPN patients by evaluating peripheral neural function. Following the Cochrane Collaboration and Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines, we conducted a meta‐analysis of the clinical trials investigating the impact of GLP‐1RA treatment on peripheral neural function in patients with DPN. Outcomes were measured using electrophysiological tests, including nerve conduction velocity (NCV) and action potential amplitude. Our meta‐analysis included six studies with 271 participants. Following GLP‐1RA treatment, NCV significantly improved compared to the control group (MD 1.74; 95% CI 1.16 to 2.33; p < 0.001) and before treatment (MD 2.16; 95% CI 1.04 to 3.27; p < 0.001). Despite the improvement in NCV, blood glucose levels did not change significantly (MD −0.20 95% CI −0.87 to 0.46, p = 0.55) indicating that GLP‐1RA enhances NCV through mechanisms other than glucose lowering. Nonetheless, as a result of the limited population studied, further research is needed to strengthen the reliability of these findings. [ABSTRACT FROM AUTHOR]

Aim: To perform a meta‐analysis comparing real‐world medication adherence to sodium–glucose cotransporter‐2 inhibitors (SGLT2is) versus glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs). Materials and Methods: A systematic search of Medline and Embase was conducted through October 2023. To meet inclusion criteria, articles had to be published in full text form and directly compare medication adherence to SGLT2is versus GLP‐1RAs in adults. Only studies evaluating real‐world data and utilizing the proportion of days covered (PDC) to measure adherence were included. Non‐adherence, defined as the proportion of patients with a PDC <80%, was the primary outcome. A subgroup analysis evaluating results among studies conducted in the United States was performed. Results: We identified eight studies evaluating 205 103 patients for inclusion. The most common country from which the data was derived was the United States (n = 5 studies). Upon meta‐analysis, we observed no difference in non‐adherence (i.e. PDC <80%) to SGLT2is versus GLP‐1RAs (relative risk = 0.86; 95% confidence interval = 0.72–1.02). In the analysis, including only US studies, SGLT2i use was associated with a 23% lower risk of non‐adherence compared with GLP‐1RA use (relative risk = 0.77; 95% confidence interval = 0.72–0.82). Conclusions: In this meta‐analysis of eight studies that included approximately 200 000 patients, there was no difference in adherence to SGLT2is versus GLP‐1RAs. However, SGLT2i use was associated with higher adherence when the analysis was limited to US studies. [ABSTRACT FROM AUTHOR]

Aim: To investigate, through post hoc analysis of nine studies from the SemaglUtide Real‐world Evidence (SURE) programme, the safety of once‐weekly (OW) semaglutide in adults with type 2 diabetes (T2D) and in subpopulations in routine clinical practice, complementing findings from the phase 3 randomized clinical trial (RCT) SUSTAIN programme. Methods: The SURE studies had a duration of ~30 weeks and included adults with diagnosed T2D treated with OW semaglutide. Safety information, including hypoglycaemic events, were collected and analysed for the total study population and for patient subgroups based on baseline patient characteristics, baseline co‐medication and prescriber specialty. Results: Of the total 3505 patients, 24.3% reported adverse events (AEs), with most patients reporting non‐serious (22.3%) and mild (17.1%) AEs. AEs mainly belonged to the gastrointestinal disorders system organ class (16.3% of patients). In total, 5.1% of patients reported AEs that led to treatment discontinuation, 0.5% reported serious adverse drug reactions and 0.2% had an AE with a fatal outcome, reported as unrelated to treatment. Overall, 1.1% and 0.1% of patients reported level 2 and 3 hypoglycaemic events, respectively. A higher rate of level 2 hypoglycaemia was observed in patients with baseline microvascular complications treated with insulin versus those on insulin without these complications. Conclusions: Safety data reported in the real‐world SURE studies were generally consistent with observations in phase 3 OW semaglutide RCTs. No new safety concerns were identified, highlighting that OW semaglutide is well tolerated by adults with T2D and in subpopulations in routine clinical practice. [ABSTRACT FROM AUTHOR]

Background and Purpose: Insulin and exenatide are two hypoglycaemic agents that exhibit different osteogenic effects. This study compared the differences between exenatide and insulin in osseointegration in a rat model of Type 2 diabetes (T2D) and explored the mechanisms promoting osteogenesis in this model of T2D. Experimental Approach: In vivo, micro‐CT was used to detect differences in the peri‐implant bone microstructure in vivo. Histology, dual‐fluorescent labelling, immunofluorescence and immunohistochemistry were used to detect differences in tissue, cell and protein expression around the implants. In vitro, RT‐PCR and western blotting were used to measure the expression of osteogenesis‐ and Wnt signalling‐related genes and proteins in bone marrow mesenchymal stromal cells (BMSCs) from rats with T2D (TBMSCs) after PBS, insulin and exenatide treatment. RT‐PCR was used to detect the expression of Wnt bypass cascade reactions under Wnt inactivation. Key Results: Micro‐CT and section staining showed exenatide extensively promoted peri‐implant osseointegration. Both in vivo and in vitro experiments showed exenatide substantially increased the expression of osteogenesis‐related and activated the LRP5/6/GSK‐3β/β‐catenin‐related Wnt pathway. Furthermore, exenatide suppressed expression of Bmpr1a to inhibit lipogenesis and promoted expression of Btrc to suppress inflammation. Conclusion and Implications: Compared to insulin, exenatide significantly improved osteogenesis in T2D rats and TBMSCs. In addition to its dependence on LRP5/6/GSK‐3β/β‐catenin signalling for osteogenic differentiation, exenatide‐mediated osteomodulation also involves inhibition of inflammation and adipogenesis by BMPR1A and β‐TrCP, respectively. [ABSTRACT FROM AUTHOR]

Objective: Many psychotropic drugs are highly associated with related weight gain. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established anti-obesity and glucose-lowering agents. Preliminary evidence also indicates they are fit for purpose in mitigating psychotropic drug-related weight gain (PDWG). This systematic review aims to synthesize the extant evidence from randomized controlled trials (RCTs) on the effects of GLP-1RAs on weight change in persons experiencing PDWG. Methods: Online databases (ie, PubMed, OVID Medline, Google Scholar) were searched to identify relevant studies from inception to January 1, 2024. Articles were screened by title, abstract, and full-text by three independent reviewers against inclusion and exclusion criteria. Results: We identified six studies with participants aged ≥18 (n=374) that were eligible for inclusion in our systematic review. Most studies reported a significant and clinically meaningful effect of GLP-1RAs on anthropometrics and/or metabolics. All RCTs replicated the finding of modest or greater effects of GLP-1RAs; the most studied agents were liraglutide and exenatide. There was insufficient literature to conduct a meta-analysis. Conclusion: Evidence suggests that GLP-1RAs are effective in mitigating weight gain in persons prescribed psychiatric medication. It is hypothesized that GLP-1RAs may moderate weight change in persons prescribed psychiatric medication through direct effects on metabolism and cognitive processes implicated in hunger/satiety. Future studies should aim to explore the long-term safety, tolerability, and efficacy profiles of various GLP-1RAs in the treatment and prevention of abnormal weight and metabolic homeostasis in psychiatric populations. [ABSTRACT FROM AUTHOR]

Objective: The aim of this meta-analysis was to investigate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on blood glucose and weight in adolescents with overweight/obesity and/or type 2 diabetes mellitus (T2DM) aged <18 years. Methods: PubMed, Embase, Web of Science, and Cochrane Library were searched for all randomized controlled trials (RCTs) up to August 2023 comparing GLP-1RAs with placebo in overweight/obese and/or T2DM adolescents and extracted relevant data for meta-analysis. Results: Fourteen RCTs were included in the meta-analysis with a total of 1,262 participants. Results revealed that the GLP-1RAs group had a more significant reduction in glycosylated hemoglobin A1c (HbA1c; risk difference (RD)=-0.34%, p<0.001) than the control group. However, there was no difference in fasting plasma glucose [fasting plasma glucose (FPG); RD=-2.07 mg/dL, p=0.065] between the two groups. Nonetheless, the experimental group that received exenatide showed no significant reduction in HbA1c (p=0.253) and FPG (p=0.611) between the two groups. The GLP-1RAs group had a more significant decline in body weight (RD=-4.28 kg, p=0.002) and body mass index (BMI) (RD=-1.63 kg/m2, p=0.002) compared to the control group. The experimental group was given liraglutide (RD=-2.31 kg, p=0.038) or exenatide (RD=-2.70 kg, p<0.001). Compared to the control group, the experimental group had a more significant drop in body weight than the control group. However, for the experimental group that received liraglutide, the BMI had a no significant reduction between the two groups (RD=-0.81 kg/m2, p=0.260). For the experimental group using exenatide, BMI declined more significantly in the intervention group than in the control group (RD=-1.14 kg/m2, p<0.001). Conclusion: This study showed that GLP-1RAs reduced HbA1c, FPG, and weight loss in overweight/obese and/or T2DM adolescents. Liraglutide was better than exenatide in terms of glucose reduction. Nevertheless, in terms of weight control, exenatide was more effective than liraglutide. [ABSTRACT FROM AUTHOR]

Binge eating disorder (BED) is the most common specific eating disorder (ED). It is frequently associated with attention deficit hyperactivity disorder (ADHD), depression, bipolar disorder (BD), anxiety disorders, alcohol and nicotine use disorder, and obesity. The aim of this narrative review was to summarize the evidence for the pharmacological treatment of BED and its comorbid disorders. We recommend the ADHD medication lisdexamfetamine (LDX) and the antiepileptic and antimigraine drug topiramate for the pharmacological treatment of BED. However, only LDX is approved for the treatment of BED in some countries. Medications to treat diseases frequently comorbid with BED include atomoxetine and LDX for ADHD; citalopram, fluoxetine, sertraline, duloxetine, and venlafaxine for anxiety disorders and depression; aripiprazole for manic episodes of BD; lamotrigine, lirasidone and lumateperone for depressive episodes of BD; naltrexone for alcohol use disorder; bupropion for nicotine use disorder; and liraglutide, semaglutide, and the combination of bupropion and naltrexone for obesity. As obesity is a frequent health consequence of BED, weight gain-inducing medications, such as the atypical antipsychotics olanzapine or clozapine, the novel antidepressant mirtazapine and tricyclic antidepressants, and the mood stabilizer valproate should be avoided where possible. It is currently unclear whether the novel and promising glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptor agonists like tirzepatide and retatrutide help with BED and its comorbidities. However, these compounds have been reported to reduce binge eating in individuals with obesity or overweight. [ABSTRACT FROM AUTHOR]

Aim: To compare the incidence of adverse events (AEs) related to antiobesity medications (AOMs; glucagon‐like peptide‐1 receptor agonists [GLP‐1RAs] vs. non‐GLP‐1RAs) after bariatric surgery. Methods: This single‐centre retrospective cohort included patients (aged 16–65 years) who had undergone laparoscopic Roux‐en‐Y gastric bypass or sleeve gastrectomy (cohort entry date) and initiated AOMs. Participants were categorized as users of US Food and Drug Administration (FDA)‐approved, off‐label, or GLP‐1RA AOMs if documented as receiving the medication on or after cohort entry date. Non‐GLP‐1RA AOMs were phentermine, orlistat, topiramate, canagliflozin, dapagliflozin, empagliflozin, naltrexone, bupropion/naltrexone and phentermine/topiramate. GLP‐1RA AOMs included: semaglutide, dulaglutide, exenatide and liraglutide. The primary outcome was AE incidence. Logistic regression was used to determine the association of AOM exposure with AEs. Results: We identified 599 patients meeting our inclusion criteria, 83% of whom were female. Their median (interquartile range [IQR]) age was 47.8 (40.9–55.4) years. The median duration of surgery to AOM exposure was 30 months. GLP‐1RAs use was not associated with higher odds of AEs: adjusted odds ratio (aOR) 1.1 (95% confidence interval [CI] 0.5–2.6) and aOR 1.1 (95% CI 0.6–2.3) for GLP‐1RA versus FDA‐approved and off‐label AOM use, respectively. AOM initiation ≥12 months after surgery was associated with lower risk of AEs compared to <12 months (aOR 0.01 [95% CI 0.0–0.01]; p < 0.001). Conclusion: Our results showed that GLP‐1RA AOMs were not associated with an increased risk of AEs compared to non‐GLP‐1RA AOMs in patients who had previously undergone bariatric surgery. Prospective studies are needed to identify the optimal timeframe for GLP‐1RA initiation. [ABSTRACT FROM AUTHOR]

The physiological effects of glucagon-like peptide-1 (GLP-1) are mainly centered on its ability to decrease blood glucose levels and facilitate satiety. Additional physiological functions have been identified by means of GLP-1 agonists such as exenatide (exendin-4; Ex4). In particular, Ex4 reduces the intake of natural and artificial rewards, effects that to some extent involve activation of GLP-1 receptors in the nucleus tractus solitarius (NTS). Although Ex4 acts in the brain, the neurochemical mechanisms underlying this activation are not fully elucidated. Investigating Ex4-induced neurochemical alterations in the nucleus accumbens (NAc) would be valuable for understanding its impact on reward-related behaviors. The aim of the present exploratory in vivo microdialysis study was therefore to study how Ex4, administered either systemically or locally into the NTS, influences classical neurotransmitters like dopamine, serotonin, noradrenaline, glutamate and GABA as well as additional players such as glycine, taurine and serine in NAc of male rats. We showed that Ex4 reduced extracellular levels of serine, taurine and glycine, where the latter two declines appear to involve activation of GLP-1R in the NTS. Besides, after systemic Ex4 injection the metabolites DOPAC, HVA, and 5HIAA are elevated. Where the increase in metabolites related to dopamine, but not serotonin, involves GLP-1 receptors in other areas than the NTS. Although the descriptive nature of the present data does not provide causality, it may however serve as an indication of mechanisms underlying how Ex4 may modulate reward-related behaviors. [ABSTRACT FROM AUTHOR]

Glucagon-like-peptide-1 (GLP-1) agonists are an emerging class of medications used to manage type 2 diabetes mellitus (T2DM) and weight loss, with demonstrated efficacy in reducing hemoglobin A1c levels, body mass index, and adverse cardiovascular events. While previous studies have reviewed notable cutaneous adverse effects with other antidiabetic medications, little is known about GLP-1 agonist-induced cutaneous reactions. Nevertheless, rare but significant cutaneous adverse reactions have been reported, including but not limited to dermal hypersensitivity reactions, eosinophilic panniculitis, bullous pemphigoid, and morbilliform drug eruptions. As GLP-1 induced cutaneous reactions are diverse, diagnosis requires clinical suspicion, thorough history-taking, and supportive histopathological findings when available. Management involves cessation of the offending agent with a tailored regimen to address inflammatory and/or immunogenic etiologies as well as irritative symptoms. This review aims to consolidate available information from case reports and case series regarding rare skin-related adverse outcomes due to GLP-1 use, aiming to provide a comprehensive overview of the presentation, pathogenesis, and management for dermatologists and other clinicians. [ABSTRACT FROM AUTHOR]