Neuroprotective effect of liraglutide and memantine in a rat model of Alzheimer’s disease

Objective:To assess the effect of memantine combined with liraglutide on aluminum chloride(AlCl_(3))and D-galactose(D-GAL)-induced neurotoxicity in rats.Methods:Male Wistar rats were divided into 5 groups of 5 animals each:the positive control,the negative control,the memantine-treated group,the liraglutide-treated group,and the combination group treated with memantine and liraglutide.AlCl_(3)and D-GAL were used to induce neurotoxicity.Behavioral tests,brain beta-amyloid protein,and oxidative stress biomarkers were evaluated.Results:The Morris water maze test indicated an enhanced memory in the combination group.Moreover,the combination treatment of liraglutide and memantine resulted in a remarkable reduction in the beta-amyloid protein level in the brain tissue.Neuronal inflammation and oxidative stress biomarkers were significantly reduced,and the levels of antioxidant parameters were enhanced.Conclusions:The combination of liraglutide and memantine exerts neuroprotective effects and enhances memory and cognitive functions in rats with Alzheimer’s disease.

Liraglutide Suppresses Myocardial Fibrosis Progression by Inhibiting the Smad Signaling Pathway

Objective Liraglutide is a commonly used hypoglycemic agent in clinical practice,and has been demonstrated to have protective effects against the development of cardiovascular disease.However,its potential role in myocardial fibrosis remains unexplored.The present study aims to assess the impact of liraglutide on the activation of cardiac fibroblasts.Methods Primary rat adult fibroblasts were isolated,cultured,and randomly allocated into 4 groups:control group,transforming growth factor beta1(TGFβ1)stimulation group,liraglutide group,and TGFβ1+liraglutide group.Fibroblast activation was induced by TGFβ1.Cell proliferation activity was assessed using the CKK-8 kit,and cellular activity was determined using the MTT kit.Reverse transcrition-quantitative polymerase chain reaction(RT-qPCR)was utilized to quantify the level of collagen transcription,immunofluorescence staining was performed to detect the expression level of type III collagen andα-smooth muscle protein(α-SMA),and immunoblotting was conducted to monitor alterations in signal pathways.Results The addition of 10,25,50 and 100 nmol/L of liraglutide did not induce any significant impact on the viability of fibroblasts(P>0.05).The rate of cellular proliferation was significantly higher in the TGFβl stimulation group than in the control group.However,the treatment with 50 and 100 nmol/L of liraglutide resulted in the reduction of TGFβl-induced cell proliferation(P<0.05).The RT-qPCR results revealed that the transcription levels of type I collagen,type III collagen,andα-SMA were significantly upregulated in the TGFβl stimulation group,when compared to the control group(P<0.05).However,the expression levels of these aforementioned factors significantly decreased in the TGFβl+liraglutide group(P<0.05).The immunofluorescence staining results revealed a significant increase in the expression levels of type III collagen andα-SMA in the TGFβl stimulation group,when compared to the control group(P<0.05).However,these expression levels significantly decreased in the TGFβl+liraglutide group,when compared to the TGFβl stimulation group(P<0.05).The Western blotting results revealed that the expression levels of phosphorylated smad2 and smad3 significantly increased in the TGFβl stimulation group,when compared to the control group(P<0.05),while these decreased in the TGFβl+liraglutide group(P<0.05).Conclusion Liraglutide inhibits myocardial fibrosis development by suppressing the smad signaling pathway,reducing the activation and secretion of cardiac fibroblasts.

Protective effect of liraglutide on the myocardium of type 2 diabetic rats by inhibiting polyadenosine diphosphate-ribose polymerase-1

BACKGROUND In recent years,studies have found that the occurrence and development of diabetic cardiomyopathy(DCM)is closely related to an increase in polyadenosine diphosphate-ribose polymerase-1(PARP-1)activity.PARP-1 activation could be involved in the pathophysiological process of DCM by promoting oxidative stress,the inflammatory response,apoptosis and myocardial fibrosis.AIM To investigate the mechanism of liraglutide in improving myocardial injury in type 2 diabetic rats,further clarified the protective effect of liraglutide on the heart,and provided a new option for the treatment of DCM.METHODS Forty healthy male SD rats aged 6 wk were randomly divided into two groups,a normal control group(n=10)and a model group(n=30),which were fed an ordinary diet and a high-sugar and high-fat diet,respectively.After successful modeling,the rats in the model group were fed a high-glucose and high-fat diet for 4 wk and randomly divided into a model group and an intervention group(further divided into a high-dose group and a low-dose group).The rats were fed a high-glucose and high-fat diet for 8 wk and then started drug intervention.Blood samples were collected from the abdominal aorta to detect fasting blood glucose and lipid profiles.Intact heart tissue was dissected,and its weight was used to calculate the heart weight index.Haematoxylin and eosin staining was used to observe the pathological changes in the myocardium and the expression of PARP-1 in the heart by immunohistochemistry.RESULTS The body weight and heart weight index of rats in the model group were significantly increased compared with those in the normal control group,and those in the intervention group were decreased compared with those in the model group,with a more obvious decrease observed in the high-dose group(P<0.05).In the model group,myocardial fibers were disordered,and inflammatory cells and interstitial fibrosis were observed.The cardiomyopathy of rats in the intervention group was improved to different degrees,the myocardial fibers were arranged neatly,and the myocardial cells were clearly striated;the improvement was more obvious in the high-dose group.Compared with the normal control group,the expression of PARP-1 in myocardial tissue of the model group was increased,and the difference was statistically significant(P<0.05).After liraglutide intervention,compared with the model group,the expression of PARP-1 in myocardial tissue was decreased,and the reduction was more obvious in the high-dose group(P<0.05)but still higher than that in the normal control group.CONCLUSION Liraglutide may improve myocardial injury in type 2 diabetic rats by inhibiting the expression of myocardial PARP-1 in a dose-dependent manner.

Short-Term Effects of Liraglutide versus Vildagliptin on Insulin Secretion and Sensitivity in Type 2 Diabetes: A Single Blinded Randomized Controlled Trial (LIRAVIS Study)

Background: We aimed to evaluate the short-term metabolic effects of a GLP-1a, (liraglutide) versus a DPP-4i, (vildagliptin) in a group of sub-Saharan type 2 diabetes patients. Methods: We conducted a randomized controlled single blinded clinical trial in 14 uncontrolled type 2 diabetes patients (HbA1c ≥ 53 mmol/mol) with mean duration of diabetes of 8 [1 - 12] years and median age of 57 [49 - 61] years. Baseline treatment consisted of metformin in monotherapy or metformin plus sulfonylureas. Participants were randomly allocated to 2 groups of add-on 1.2 mg/day subcutaneous liraglutide in group 1 or 100 mg/day of oral vildagliptin in group 2 for 2 weeks. In all participants, insulin secretion in response to mixed meal tolerance test, insulin sensitivity by 80 mU/m2/min hyperinsulinemic-euglycemic clamp, body composition, and lipid profile were measured before and after intervention. Results: At the end of intervention, insulin sensitivity remained unchanged both with liraglutide from 6.6 [4.2 - 7.9] to 6.9 [4.3 - 10.8] mg/kg/min;p = 0.61 and vildagliptin from 7.1 [5.3 - 9.0] to 6.5 [5.6 - 9.4] mg/kg/min (p = 0.86). The area under the C-peptide curve varied from 5.5 [1.0 - 10.9] to 14.9 [10.8 - 17.2] nmol/L/120min, p = 0.09 in group 1 and from 1.1 [0.5 - 14.1] to 13.0 [9.6 - 16.9] nmol/L/120min (p = 0.17) in group 2. LDL Cholesterol levels decreased significantly with liraglutide from 0.85 g/L [0.51 - 1.02] to 0.54 g/L [0.50 - 0.73] (p = 0.04) but not with Vildagliptin. Body weight tended to decrease in group 1 (−0.6 kg) versus modest increase in group 2 (+1.1 kg). Conclusion: Short-term metabolic effects of Liraglutide and Vildagliptin add-on therapy are comparable in sub-Saharan type 2 diabetes patients with a more favorable trend for Liraglutide on body weight, lipid profile, and insulin secretion.

A Study on Enhancing Pancreatic Islet Function in Type 2 Diabetes and Coronary Heart Disease Patients with Liraglutide and Metformin Combination Therapy

Objective:To investigate the impact of combining liraglutide with metformin on the enhancement of pancreatic islet function in patients with type 2 diabetes and coronary heart disease.Methods:60 patients with type 2 diabetes and coronary heart disease admitted from February 2022 to August 2023 were selected as research subjects.They were randomly assigned to either control or treatment groups,with 30 patients in each.The control group received metformin alone,while the treatment group received liraglutide in combination with metformin.Various indicators,including blood sugar levels,pancreatic islet function,and cardiac function between the two groups were compared.Results:The results of FPG,2hPG,HbA1c,HOMA-IR,NT-proBNP,and LVEDD in the treatment group were lower than those in the control group,whereas the values of FINS,HOMA-β,E/A,and LVEF in the treatment group were higher than those in the control group(P<0.05).Conclusion:The use of liraglutide in combination with metformin significantly benefits patients with type 2 diabetes and coronary heart disease.It leads to improved pancreatic islet function,better blood sugar control,and enhanced cardiac function.This combination therapy is recommended for clinical adoption.

Cost-effectiveness Analysis of Insulin Degludec and Liraglutide Injection in the Treatment of Type 2 Diabetes

Objective To analyze the cost-effectiveness of insulin degludec and liraglutide injection(IDegLira)compared with insulin glargine plus insulin aspart(IGar plus IAsp)in the treatment of type 2 diabetes mellitus(T2DM)based on the price of IDegLira before and after it was successfully admitted to the National Reimbursable Drug List(NRDL).Methods Cost and effectiveness parameters were obtained through systematic retrieval from PubMed,ScienceDirect,CNKI,and Wanfang database.A cost-effectiveness analysis(CEA)model was established to analyze the economics using IDegLira for T2DM patients with 1 to 5 years of medication.Results and Conclusion Before IDegLira was admitted to NRDL,its economic advantages over the IGlar plus Iasp regimen became more significant as patients’medication time prolonged.After being admitted to NRDL,with 1 year of medication,the medical cost of IDegLira decreased by 2853.91 yuan and the quality adjusted life years(QALY)increased by 0.12055 than IGar plus IAsp.The sensitivity analysis was highly consistent with the results of the baseline result.After being admitted to NRDL,for patients with T2DM who have poor blood glucose control,IDegLira is absolutely an economic advantage scheme compared with IGar plus IAsp.

Liraglutide治疗2型糖尿病的临床效果

目的探讨Liraglutide治疗2型糖尿病(T2DM)的临床效果。方法 28例T2DM患者在应用二甲双胍治疗的基础上给予Liraglutide,治疗16周。观察Liraglutide治疗前后糖化血红蛋白(HbA1c)、空腹血糖(FPG)、餐后2h血糖(2hPG)、空腹血浆胰岛素(FINS)水平、血脂、血压、体质量指数(BMI)、胰岛素抵抗指数(HOMA-IR)及β细胞功能指数(HOMA-IS)的变化及低血糖事件和其他不良事件的发生率。结果 Liraglutide治疗后T2DM患者HbA1c、FPG、2hPG和BMI均较治疗前显著减低,差别有统计学意义(P<0.01);HOMA-IS较治疗前升高,差别有统计学意义(P<0.01)。Liraglutide治疗未出现严重不良反应。结论 Liraglutide治疗T2DM是安全有效的。

cAMP在Liraglutide改善Aβ25-35诱导的昼夜节律紊乱中的作用研究

目的研究环腺苷酸(cAMP)在利拉鲁肽(Liraglutide)改善β淀粉样蛋白25-35(Aβ25-35)引起的昼夜节律紊乱中的作用。方法 C57BL/6小鼠随机分为Vehicle,Aβ25-35,Liraglutide,Liraglutide+Aβ25-35四组,利用跑轮行为学实验评估小鼠昼夜节律,ELISA法检测海马CA1区cAMP的表达水平。HT22小鼠海马神经细胞随机分为Vehicle,Aβ25-35,Liraglutide,Liraglutide+Aβ25-35,SQ22536+Liraglutide+Aβ25-35,SQ22536组,利用CCK8法检测细胞存活率,实时荧光定量PCR检测per1 mRNA表达水平。结果海马内注射Aβ25-35后小鼠出现明显昼夜节律紊乱,且cAMP节律性表达异常,Liraglutide预处理明显改善了小鼠昼夜节律紊乱现象和cAMP节律性表达异常。HT22细胞中加入Aβ25-35后,细胞存活率下降且per1基因节律性表达异常,而Liraglutide预处理提高了细胞存活率并改善了per1表达异常,但这种效应会被cAMP抑制剂SQ22536所拮抗。结论 Liraglutide可拮抗Aβ25-35所致昼夜节律紊乱及per1基因的异常表达,其机制可能是通过改变cAMP节律性表达实现的。

Gut-brain connection: The neuroprotective effects of the anti-diabetic drug liraglutide

Long-acting glucagon-like peptide-1(GLP-1) analogues marketed for type 2 diabetes(T2D) treatment have been showing positive and protective effects in several different tissues, including pancreas, heart or even brain. This gut secreted hormone plays a potent insulinotropic activity and an important role in maintaining glucose homeostasis. Furthermore, growing evidences suggest the occurrence of several commonalities between T2 D and neurodegenerative diseases, insulin resistance being pointed as a main cause for cognitive decline and increased risk to develop dementia. In this regard, it has also been suggested that stimulation of brain insulin signaling may have a protective role against cognitive deficits. As GLP-1 receptors(GLP-1R) are expressed throughout the central nervous system and GLP-1 may cross the blood-brain-barrier, an emerging hypothesis suggests that they may be promising therapeutic targets against brain dysfunctional insulin signaling-related pathologies. Importantly, GLP-1 actions depend not only on the direct effect mediated by its receptor activation, but also on the gut-brain axis involving an exchange of signals between both tissues via the vagal nerve, thereby regulating numerous physiological functions(e.g., energy homeostasis, glucose-dependent insulin secretion, as well as appetite and weight control). Amongst the incretin/GLP-1 mimetics class of anti-T2 D drugs with an increasingly described neuroprotective potential, the already marketed liraglutide emerged as a GLP-1R agonist highly resistant to dipeptidyl peptidase-4 degradation(thereby having an increased half-life) and whose systemic GLP-1R activity is comparable to that of native GLP-1. Importantly, several preclinical studies showed anti-apoptotic, anti-inflammatory, anti-oxidant and neuroprotective effects of liraglutide against T2 D, stroke and Alzheimer disease(AD), whereas several clinical trials, demonstrated some surprising benefits of liraglutide on weight loss, microglia inhibition, behavior and cognition, and in AD biomarkers. Herein, we discuss the GLP-1 action through the gut-brain axis, the hormone's regulation of some autonomic functions and liraglutide's neuroprotective potential.

Liraglutide reduces oxidized LDL-induced oxidative stress and fatty degen- eration in Raw 264.7 cells involving the AMPK/SREBP1 pathway

Baekgound Recent studies have suggested a potential role for liraglutide in the prevention and stabilization ofatherosclerotic vascular disease. However, the molecular mechanisms underlying the effect of liraglutide on atherosclerosis have not been well elucidated. The pur- pose of this study was to examine whether liraglutide protects against oxidative stress and fatty degeneration via modulation of AMP-activated protein kinase （AMPK）/sterol regulatory element binding transcription factor 1 （SREBP1） signaling pathway in foam ceils. Methods Mouse macrophages Raw264.7 cells were exposed to oxidized low density lipoprotein （oxLDL） to induce the formation of foam cells. The cells were incubated with oxLDL （50 μg/mL）, liraglutide （0.1, 0.5, 1 and 2 nmol/L） or exendin-3 （9-39） （1, 10 and 100 nmol/L） alone, or in combination. Oil Red O staining was used to detect intracellular lipid droplets. The levels of TG and cholesterol were measured using the commercial kits. Oxidative stress was determined by measuring intracellular reactive oxygen species （ROS）, malondialdehyde （MDA） and superoxide dismutase 1 （SOD）. Western blot analysis was used to examine the expression of AMPKal, SREBP1, phosphory- lated AMPKal, phosphorylated SREBP1, glucagon-like peptide-1 （GLP-1） and GLP-1 receptor （GLP-1R）. Results Oil Red O staining showed that the cytoplasmic lipid droplet accumulation was visibly decreased in foam cells by treatment with liraglutide. The TG and cholesterol content in the liraglutide-treated foam cells was significantly decreased. In addition, foam ceils manifested an impaired oxidative stress following liraglutide treatment, as evidenced by increased SOD, and decreased ROS and MDA. However, these effects of liraglutide on foam cells were attenuated by the use of GLP-IR antagonist exendin-3 （9-39）. Furthermore, we found that the expression level of AMPKa 1 and phosphorylated AMPKct 1 was significantly increased while the expression level of SREBP 1 and phosphorylated SREBP 1 was significantly decreased in foam cells following treatment with liraglutide. Conclusions This study for the first time demonstrated that the effect of liraglutide on reducing oxidative stress and fatty degeneration in oxLDL-induced Raw264.7 cells is accompanied by the alteration of AMPK/SREBP1 pathway. This study provided a potential molecular mechanism for the effect of liraglutide on reducing oxidative stress and fatty degeneration.

Liraglutide directly protects cardiomyocytes against reperfusion injury possibly via modulation of intracellular calcium homeostasis

Background Liraglutide is glucagon-like peptide-1 receptor agonist for treating patients with type 2 diabetes mellitus. Our previous studies have demonstrated that liraglutide protects cardiac function through improving endothelial function in patients with acute myocardial infarction undergoing percutaneous coronary intervention. The present study will investigate whether liraglntide can perform direct protective effects on cardiomyocytes against reperfusion injury. Methods In vitro experiments were performed using H9C2 cells and neonatal rat ventricular cadiomyocytes undergoing simulative hypoxia/reoxygenation （H/R） induction. Cardiomyocytes apoptosis was detected by fluorescence TUNEL. Mitochondrial membrane potential （AWm） and intracellular reactive oxygen species （ROS） was assessed by JC-1 and DHE, respectively. Fura-2/AM was used to measure intracellular Ca2＋ concentration and calcium transient. Immtmofluorescence staining was used to assess the expression level of sarcoplasmic reticulum Ca2＋-ATPase （SERCA2a）. In vivo experiments, myocardial apoptosis and expression of SERCA2a were detected by colorimetric TUNEL and by immunofluorescence staining, respectively. Results In vitro liraglutide inhibited cardiomyotes apoptosis against H/R. △mψ of cardiomyocytes was higher in liraglntide group than H/R group. H/R increased ROS production in H9C2 cells which was attenuated by liraglutide. Liraglutide significantly lowered Ca2＋ overload and improved calcium transient compared with H/R group, lmmunofluorescence staining results showed liraglutide promoted SERCA2a expression which was decreased in H/R group. In ischemia/reperfusion rat hearts, apoptosis was significantly attenuated and SERCA2a expression was increased by liraglutide compared with H/R group. Conclusions Liraglutide can directly protect cardiomyocytes against reperfusion injury which is possibly through modulation of intracellular calcium homeostasis.

Effect of liraglutide on endoplasmic reticulum stress in the renal tissue of type 2 diabetic rats

BACKGROUND Liraglutide is a glucagon-like peptide 1 receptor agonist analog that has been found to have a therapeutic effect in diabetes.In addition to its ability to treat diabetes,liraglutide has beneficial effects on the cardiovascular system and kidney as well as other beneficial effects,but its specific mechanism is not clear.In this study,a rat model of type 2 diabetes was established by administration of a high-sugar,high-fat diet combined with low-dose streptozotocin(STZ)to observe the effect of liraglutide on the kidneys of type 2 diabetes rats and the possible underlying mechanisms.AIM To explore whether liraglutide has a protective effect on type 2 diabetic rat kidneys and the underlying mechanisms.METHODS Eight-week-old male Sprague-Dawley rats were randomly divided into a control group,model group,low-dose liraglutide group,and high-dose liraglutide group.Control rats were fed a standard diet,while model group and intervention group rats were fed high-sugar,high-fat feed for 1 mo and then intraperitoneally injected with 40 mg/kg STZ to induce type 2 diabetes.The low-dose and highdose intervention groups received 100μg/kg and 200μg/kg liraglutide,respectively,once daily by subcutaneous injection.The control and model groups were given an equivalent volume of physiological saline for 8 wk.Pathological changes in renal tissues were observed by hematoxylin and eosin staining and periodic acid-Schiff staining,and GRP78 and caspase-12 expression was detected by Western blot and reverse transcription-polymerase chain reaction(RT-PCR).RESULTS Western blot analysis showed that GRP78 and caspase-12 protein expression in kidney tissue was significantly higher in model rats than in normal rats and lowerin the liraglutide-treated groups than in the model group,with a more significant decrease being observed in the high-dose group than in the low-dose group.RTPCR showed that the mRNA expression of GRP78 and caspase-12 was higher in model rats than in control rats and lower in the liraglutide-treated groups than in the model group,with the high-dose group exhibiting a more significant decrease than the low-dose group.CONCLUSION Liraglutide may delay the progression of diabetic nephropathy by reducing endoplasmic reticulum stress and protect the kidneys in a dose-dependent manner.

Mimicking natural cholesterol assimilation to elevate the oral delivery of liraglutide for type Ⅱ diabetes therapy

Glucagon-like peptide-1 receptor agonists(GLP-1 RA)are a series of polypeptides broadly applied in the long-term treatment of typeⅡdiabetes.However,administration of GLP-RA is mainly through repetitive subcutaneous injection,which may seriously decrease the compliance and safety.Herein,a bio-inspired oral delivery system was designed to enhance the oral absorption of liraglutide(Lira),a kind of GLP-1 RA,by mimicking the natural cholesterol assimilation.25-hydroxycholesterol(25HC),a cholesterol derivative,was modified on the surfaced of Lira-loaded PLGA nanoparticles(Lira 25HC NPs)and functioned as a“top-down”actuator to facilitate unidirectional transcytosis across the intestinal epithelium.After oral delivery,Lira 25HC NPs displayed improved therapeutic effect as compared with oral free Lira on typeⅡdiabetes db/db mice,as evidenced by multiple relieved diabetic symptoms including the enhanced glucose tolerance,repressed weight growth,improved liver glucose metabolism,decreased fasting blood glucose,HbA 1c,serum lipid,and increasedβcells activity.Surprisingly,the fasting blood glucose,liver glucose metabolism,and HbA1c of oral Lira-loaded 25HC NPs were comparable to subcutaneous injection of free Lira.Further mechanisms revealed that 25HC ligand could mediate the nanoparticles to mimic natural cholesterol absorption by exerting high affinity towards apical Niemann-Pick C1 Like 1(NPC1L1)and then basolateral ATP binding cassette transporter A1(ABCA1)overexpressed on the opposite side of intestinal epithelium.This cholesterol assimilation-mimicking strategy achieve the unidirectional transport across the intestinal epithelium,thus improving the oral absorption of liraglutide.In general,this study established a cholesterol simulated platform and provide promising insight for the oral delivery of GLP-1 RA.

Effects of liraglutide on metabolic syndrome in WBN/Kob diabetic fatty rats supplemented with a high-fat diet

Background:Liraglutide,a GLP-1 receptor agonist,has recently been used to treat metabolic syndrome(MS)because of its anti-diabetic and anti-obesity effects.We have previously shown that Wistar Bonn Kobori diabetic and fatty(WBN/Kob-Leprfa,WBKDF)rats fed a high-fat diet(HFD)developed MS including marked obesity,hyperglycemia,and dyslipidemia.To obtain further information on WBKDF-HFD rats as a severe MS model,we performed a pharmacological investigation into the anti-MS effects of liraglutide in this model.Methods:Seven-week-old male WBKDF-HFD rats were allocated to three groups(n=8 in each group):a vehicle group,a low-dose liraglutide group,and a high-dose liraglutide group.They received subcutaneous injections of either saline or liraglutide at doses of 75 or 300μg/kg body weight once daily for 4 weeks.Results:Results showed that liraglutide treatment reduced body weight gain and food intake in a dose-dependent manner.The marked hyperglycemia and the glucose tolerance were also significantly ameliorated in the liraglutide-treated groups.Moreover,liraglutide also reduced the plasma triglyceride concentration and liver fat accumulation.Conclusions:The present study demonstrated that liraglutide could significantly alleviate MS in WBKDF-HFD rats,and the reaction to liraglutide is similar to human patients with MS.WBKDF-HFD rats are therefore considered to be a useful model for research on severe human MS.

Successful treatment of hyperglycemia with liraglutide in a hospitalized 27-year-old patient with schizophrenia:A case report

BACKGROUND Antipsychotics are associated with abnormalities in glucose metabolism in patients with schizophrenia. Liraglutide, a GLP-1 receptor agonist, is Food and Drug Administration approved for the treatment of type 2 diabetes mellitus. However, ways to maintain the long-term stability of psychotic symptoms and balance the disadvantages of obesity, diabetes, and other metabolic disorders caused by antipsychotic medications remain unclear. In this study, we present a case of weight gain and hyperglycemia in a schizophrenia patient who received antipsychotic polypharmacy for 6 years.CASE SUMMARY A 27-year-old man with olanzapine and sodium valproate-treated disorganized schizophrenia was admitted to a diabetes outpatient clinic. He was diagnosed with type 2 diabetes(fasting blood glucose, 20 mmol/L) and obesity(body mass index, 38.58 kg/m). The patient had been treated with glargine(40 IU/d) and metformin(1.5 g/d) and showed a poor response for 2 mo. Two years of liraglutide treatment resulted in stable blood glucose levels and weight loss in addition to a maintained stable mental status for a long time. The biological activities of GLP-1 significantly improved glucose levels and body weight in the schizophrenia patient treated with antipsychotic medications.CONCLUSION Liraglutide administration can be considered an effective alternative treatment for abnormalities in glucose metabolism in schizophrenia patients receiving antipsychotics.

Cost-Utility Analysis of Liraglutide in Type 2 Diabetes Patients in China after Chinese Reformation of Medical Care System

Objectives: The cost-utility analysis of Liraglutide is aimed at evaluating whether Liraglutide is cost-effective or not after Chinese reformation on medical insurance. The analysis is based on the results of clinical trial conducted in Asia. Methods: We applied a Markov model to estimate the quality-adjusted life years, medical cost and incidence of diabetes-related complications for patients receiving the Liraglutide as an add-on to the metformin treatment. Baseline characteristics were taken from a China’s study while the treatment effect is from an Asian study. The related medical cost and utility score were obtained from a local study in China. Having set 30 years’ simulations, the incremental cost-effectiveness ratio was calculated comparing with glimepiride treatment. The ratio would be compared with the willingness to pay for a quality-adjusted-life-year (QALY) which is three times of the GDP per capita in Beijing. Sensitivity analysis was also performed. Result: During a period of 30 years, the base-case analysis which takes discount rate at 3% shows that Liraglutide 1.8 mg results in an average incremental cost of CNY 82,671.49, an improvement in 0.12 QALYs and a reduction of incidence of diabetes-related complications comparing to glimepiride. The associated incremental cost-effectiveness ratio is CNY 688,929.08. Conclusion: Long-term project shows that taking Liraglutide as an add-on to the metformin treatment will lead to increasing quality-adjusted life years and reduction of incidence of diabetes-related complications. When the price of Liraglutide is reduced by 43 percent in China’s yuan, Liraglutide will be cost-effective in China from the healthcare system perspective taking three times of GDP per capita as our WTP threshold.

Liraglutide as Add-on to Oral Antidiabetic Agents or Insulin in Routine Practice of Patients with Type 2 Diabetes

Aims: To evaluate in a real-word routine-care practice the effect of liraglutide as add-on treatment in type 2 diabetic patients treated with oral antidiabetic agents and/or insulin. Methods: A retrospective study from 3 outpatient clinics in Copenhagen, Denmark, of all patients (n = 534) initiating treatment with liraglutide. 346 patients were treated ≥3 months. Excluded from analysis were: 107 patients changing from exenatide and 83 due to lack of clinical response or adverse events. Results: In 149 patients liraglutide was add-on to oral antidiabetic agents, most often metformin plus sulfonylurea (n = 86). Mean follow-up: 7.3 ± 3.0 months. HbA1c reduction: 1.3% ± 1.5% (15 ± 16 mmol/mol) from a baseline of 8.7% ± 1.5% (71 ± 16 mmol/mol). Weight reduction: –3.5 ± 4.9 kg from 105.2 ± 21.3 kg. Sulfonylurea treatment was stopped/dose reduced in 57% of these patients. In 114 patients liraglutide was add-on to insulin. Mean follow-up: 7.0 ± 3.1 months. HbA1c reduction: 0.8% ± 1.2% (8 mmol/mol) from a baseline of 8.7% ± 1.5% (71 ± 16 mmol/mol). Weight reduction: –5.1 ± 4.9 kg from 109.2 ± 22.1 kg. Baseline insulin dose of 83 ± 59 U/day was reduced by 28 ± 36 U/day. Insulin therapy could be stopped in 19% of these patients. Conclusions: Effects on HbA1c and weight of liraglutide as add-on to oral antidiabetic agents were not different from results previously published in randomised trials. Adding liraglutide to existing insulin regimens is an attractive treatment strategy in obese type 2 diabetic patients.

Liraglutide and Dulaglutide Have Comparable HbA1c Reduction in Emirati Patients with T2DM

Glucagon like peptide-1 is responsible for the incretin effect after a meal or an oral glucose load. Patients with type 2 diabetes mellitus have impairment of secretion and action of glucagon like peptide-1. This impairment can be overcome through pharmacological doses of glucagon like peptide-1 analogues. Aim of the Study: This study aimed at evaluation of the effect of treatment with glucagon like peptide-1 analogues;liraglutide and dulaglutide, in Emirati patients with type 2 diabetes mellitus. Glycemic control was the primary end point while the secondary end point was the effect on body mass index, blood pressure, heart rate, serum creatinine, lipid profile and estimated glomerular filtration rate. Patients & Methods: This is a retrospective study including 54 patients with type 2 diabetes mellitus. Patients used Liraglutide or Dulaglutide as add on therapy to oral antidiabetic medications for one year. Thirty-four patients used liraglutide 1.8 mg once daily and 20 patients used dulaglutide 1.5 mg once weekly. All patients were older than 18 years and had estimated glomerular filtration rate (>90 ml/min/1.73 m2). Body mass index, sitting blood pressure and heart rate were collected. Fasting plasma glucose, HbA1c, lipid panel and other biochemical parameters were also collected. Data were analysed before and at 6 and 12 months of glucagon like peptide-1 analogue treatment. Results: At 12 months of treatment, liraglutide significantly reduced fasting plasma glucose (11.3 ± 4 vs 7 ± 1.7, p < 0.001), HbA1c (8.55 ± 1.6 vs 7.18 ± 1.04, p < 0.001) and body mass index (39.4 ± 6.4 vs 37.6 ± 6.7, p < 0.0005). Dulaglutide did not significantly reduce fasting plasma glucose (15.4 ± 3.5 vs 9.5 ± 5.4 mmol/L, p = 0.053), significantly reduced HbA1c (8.84 ± 1.8 vs 7.5 ± 0.79, p = 0.007), body mass index (38.8 ± 6.8 vs 37.2 ± 6.6, p = 0.004) and estimated glomerular filtration rate (123.6 ± 60 vs 104 ± 47.3, p = 0.008). Dulaglutide was more effective in reduction of body mass index than liraglutide. Both drugs did not show significant effect on blood pressure, heart rate or lipid profile. Conclusion: Over a period of one year, liraglutide and dulaglutide produced comparable reduction of HbA1c and hence diabetes control. Both drugs significantly reduced body mass index but this effect was more pronounced with Dulaglutide. Only liraglutide significantly reduced fasting plasma glucose. Dulaglutide significantly reduced estimated glomerular filtration rate. There was no significant effect of liraglutide or dulaglutide on blood pressure, heart rate or lipid profile.

Liraglutide (Saxenda®) as a Treatment for Obesity

Obesity is a significant concern in the United States, affecting approximately 35% of the population. Comorbidities, such as diabetes, hypertension, and hyperlipidemia, significantly increase one’s risk of heart attack, stroke, and even death. Liraglutide, a medication originally used to treat diabetes, has been approved for the treatment of obesity. Clinical trials have shown significant improvements in body weight and body mass index (BMI) at a dose of up to 3.0 mg daily. The most common adverse effects are gastrointestinal in nature, however, these often subside with time. Safety concerns with regards to thyroid tumors and pancreatitis should be carefully considered prior to use of this agent. Liraglutide should be considered an additional tool in the treatment of obesity, especially in patients with concomitant diabetes.